Background: COVID-19 vaccines have been linked to myocarditis which in some circumstances can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. Methods: We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-related myocarditis through July 3^rd, 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included, without imposing any additional restrictions. Causality in each case was determined by three independent reviewers with cardiac pathology experience and expertise. Results: We initially identified 1,691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In 2 cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome (MIS). The mean and median number of days from last COVID-19 vaccination until death was 6.2 and 3 days, respectively. Most of the deaths occurred within a week from the last injection. We established that all 28 deaths were causally linked to COVID-19 vaccination by independent adjudication. Conclusions: The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death from suspected myocarditis in cases where sudden, unexpected death has occurred in a vaccinated person. Urgent investigation is required for the purpose of risk stratification and mitigation in order to reduce the population occurrence of fatal COVID-19 vaccine-induced myocarditis.

Nerve hydrodissection (HD), a technique used when treating nerve entrapments, involves using an anesthetic or solution such as saline or 5% dextrose solution to separate the nerve from the surrounding tissue, fascia, or adjacent structures. This technique aims to treat neuropathic pain, or pain caused by the nerve. Ultrasound-guided HD of peripheral nerves has gained significant attention in the medical profession and pain management fields in recent years. This is due to a number of high impact publications of randomized control trials demonstrating the efficacy and safety of this technique for the treatment of carpal tunnel syndrome. Even the 20th edition of Harrison’s Principles of Internal Medicine textbook lists injection of 5% dextrose as an alternative local treatment that does not have the side effects of corticosteroids. At present, there is no review of the current literature on this technique. This manuscript will summarize and discuss the following: 1) the different approaches to doing ultrasound-guided HD of nervous structures, 2) its usages in different clinical situations, 3) its clinical pearls, 4) the solution used, and 5) the postulated mechanisms of action.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

Objective: To explore the efficacy and safety of breathing exercises for pain management in cancer survivors. Design: A systematic review. Data sources: Thirteen databases, including PubMed, EMBase, CENTRAL, Medline, CINAHL, JBI, Science Direct, Scopus, SocINDEX, Web of Science, PsycINFO, CNKI, and Wan Fang, were searched from inception to May 24, 2021. Review/analysis methods: Studies that focused on the efficacy of breathing exercises for pain management in cancer survivors were included. Cochrane tools were used for the quality appraisal of the included studies. Due to the heterogeneity of the studies, descriptive data analysis was used to summarize the results. Results: A total of 10 studies were included in this systematic review. Slow pursed lip breathing showed benefits for post-surgical pain. Contradictory findings were identified in the Enhanced Recovery After Surgery breathing exercise for post-surgical pain. Slow deep breathing and Hey-Hu regular breathing techniques were effective for pain management in pediatric cancer patients. The Active Cycle of Breathing Technique and five-minute mindful breathing did not have any statistically significant effects on pain relief. Quality of life was measured in three studies, with some improvement. Only one study addressed adverse events and reported that no adverse events associated with the breathing exercises occurred during the study. Conclusion: This review found some evidence of positive effects of breathing exercises for pain relief in cancer survivors. However, the unsatisfactory methodological quality of the studies prevents its generalizability. More large-scale studies are needed to assess the efficacy and safety of breathing exercises for pain relief in cancer survivors.

While the majority of previous studies assessing pain-related variables in psychopaths used electric shocks, little is known about the effectiveness of alternative pain-inducing methods to increase emotional responses such as fear and anxiety. A small sample of healthy undergraduate men (N = 15) was recruited to assess the effectiveness of a heat stimulus to induce pain in an immediate versus delayed punishment paradigm. Although pain catastrophizing, anxiety, and threat of pain did not increase throughout the experiment, participants experienced a significant increase of fear of pain and pain intensity, indicating that the heat stimulus was effective in inducing pain. Furthermore, subjects were slower in initiating the pain stimulus during the first five trials, but no time difference was found during the 15 remaining trials. No correlation was found between psychopathic traits and pain-related variables, with the exception of inconsistent results within the Fearless Dominance factor. Findings are discussed in terms of improvement for a larger scale study involving psychopathic individuals.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animals models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.

Many patients with Coronavirus disease 2019 (COVID-19) suffer from shortness of breath and severe chest pain. Here we report successful therapy of a patient with diagnosis of COVID-19, severe chest pain and significant shortness of breath, using radial extracorporeal shock wave therapy (rESWT). The latter started seven days after beginning of symptoms and drug therapy without success, and involved daily application of 15.000 to 20.000 radial extracorporeal shock waves over the intercostal muscles as well as the paravertebral muscles of the thoracic and lumbar spine, diaphragm and flanks. Immediately after the first rESWT session the patient experienced significant pain relief and improvement of breathing. Four days later the pain had completely subsided and breathing was largely normalized. This type of noninvasive, non-pharmacologic treatment could help many COVID-19 patients or patients who still suffer from breathing problems weeks after having been infected with SARS-CoV-2, giving them back quality of life.

The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of aminoacids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µ-O CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperxcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions.

Animals’ facial expressions have been widely used as a readout for emotion. Scientific interest in the facial expressions of laboratory animals has centered primarily on negative experiences, such as pain, experienced as a result of scientific research procedures. Recent attempts to standardize evaluation of facial expressions associated with pain in laboratory animals has culminated in the development of “grimace scales”. In the context of laboratory animals, these have been developed and evaluated for mice, rats, rabbits, sheep, and ferrets. The prevention or relief of pain in laboratory animals is a fundamental requirement for in vivo research to satisfy community expectations. However, to date it appears that the grimace scales have not seen widespread implementation as clinical pain assessment techniques in biomedical research. In this review, we discuss some of the barriers to implementation of the scales in clinical laboratory animal medicine, progress made in automation of collection, and suggest avenues for future research.

For decades, neurologic and other extra glandular manifestations have been described in Sjögren’s syndrome (SS). More recently, neuropathic, psychological and cognitive alterations are being considered part of the disease. The lacrimal glands (LG), the ocular surface (OS), salivary glands (SG) and the central nervous system (CNS) are integrated to modulate the autonomic functions and, not just those organs, but also the hippocampus, which is linked to the autonomic nervous system, and modulate behavior responses appears to be compromised in the SS. Recent studies confirm that the tryptophan/kynurenine pathway (TKP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating the indoleamine-pyrrole 2,3-dioxygenase (IDO) in SS. This pathway interferes on serotonergic and glutamatergic neurotransmission, mostly in the hippocampus, and other structures of the CNS. Although not demonstrated, it is plausible that this constant interference induces clinical signs of SS, and contributes to the discrepancy between symptoms and signs, towards manifestations of hyperalgesia and depression in patients with SS. Therapeutic strategies are being reexamined and new options designed and tested to regulate the involved steps of the TKP. In the future, the application of this concept may offer a clue to the mosaic of manifestations of SS.

This study evaluated the effect of low-level laser irradiation induces by diode laser on the speed of orthodontic tooth movement of canines submitted to initial retraction. Twenty-four mandibular canines were retracted by using NiTi spring (force of 150 g/side). Thirteen of those were irradiated with a diode laser 980-nm diode laser (Wiser Laser Doctor Smile, Lambda) operating at an 810-nm wavelength (1 W of output power, continuous wave of 66.7 J/cm2) that was equipped with a 0.6-mm optical fiber in continuous-wave mode. The canine retraction was accomplished by using prefabricated coil springs. The right of the mandible was chosen to be irradiated with the laser, whereas the left side was considered the control without laser irradiation. The laser was applied with 0-, 3-, 7-, and 14-day intervals. The amount of canine retraction was measured with a digital electronic caliper while the pain level was prompted by a patient questionnaire. The speed of tooth movement was significantly greater in the laser group than in the control group. The pain intensity was also at a lower level in the laser group. Our findings suggest that diode laser therapy can highly accelerate tooth movement during orthodontic treatment and can also effectively reduce pain level.

Mint and to a lesser extent menthol have been used since antiquity for medicinal purposes. Key components of mint and menthol use such as composition and intake, safety and traditional uses are discussed prior to a review of clinical and human performance outcomes in the areas of digestive and respiratory health; antibacterial and anti-fungal properties, nocioception, migraine and headache and emerging evidence regarding COVID 19. Evidence suggests benefit for patients with irritable bowel syndrome and related digestive issues, with analgesic and respiratory effects also noted. Perceptual characteristics relating to thermal comfort and sensation, taste sensitivity and alertness are also considered; these effects are predominantly driven by stimulation of transient receptor potential melastatin 8 (TRPM8) activity resulting in sensations of cooling and freshness, with lesser influence on thirst. Finally, sport performance is considered as a domain that may further elucidate some of the aforementioned underpinning outcomes due to its systemic and dynamic nature, especially when performed in hot environmental conditions.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

The diversity and inclusion discussion permeates many sectors of society. Within this dialogue, science and scientists are acutely aware of the value of diversity and the need for inclusion. While demographic diversity in science has received considerable recent attention, very little research and understanding exists on inclusion. Our study presents empirical data on the meaning of inclusion using a crowdsourcing approach that sought responses to the question “What does inclusion mean to you?”. The most prominent concepts were those of empathy, warmth, support, love, acceptance and curiosity; diverse perspectives; and participation. We clustered conceptual elements of inclusion into four themes: access and participation, embracing diverse perspectives, a welcome environment, and team belonging. On the basis of these data, we theorize a conceptual framework model from which inclusion may be put into practice. Our model suggests a dynamic process of inclusion operating from principal structural elements of 1) a foundation that involves place, access and participation, and space; 2) reciprocal engagement as an engine for inclusion; and 3) expression of inclusion as culture. The framework model demonstrates a means by which the practice of diversity can be more than shifts in demographic statistics, and instead promote the full expression of benefits derived when the many dimensions of diversity are truly included.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

Temporomandibular disorders (TMD) is a group of orofacial pain conditions which is the most common non-dental pain complaint in the maxillofacial region. Due to the complexity of the etiology and often cyclical nature of the disease, the diagnosis and management of TMD remain a challenge where consensus is still lacking in many aspects. While clinical examination is considered the most important process in the diagnosis of TMD, imaging may serve as a valuable adjunct in selected cases. Depending on the type of TMD, many treatment modalities have been proposed, ranging from conservative options to open surgical procedures. In this review, the authors discuss the present thinking in the etiology and classification of TMD, followed by the diagnostic approach and the current trend and controversies in management.

Background: Low-level physical activity (PA) among Chronic Low Back Pain (cLBP) is associated with various biopsychosocial factors. This research aimed to study the predictors of PA behavior among cLBP patients. Methods: In the present study 300 eligible patients with cLBP who referred to comprehensive health service centers in the Shahid Beheshti University of Medical Sciences (SBUMS) in Tehran, Iran were random selected.To diagnose the predictors of PA behavior, all the Theory of Reasoned Action (TRA) constructs were examined as risk factors to see if they influence on the probability of PA behavior occurrence and were interpreted through odds ratio (OR). SPSS version 19 was used to analyze the data. Results: Totally 280 cLBP patients with mean age of 57.07 ±13.09 years old participated in the study. This study showed that motivation to comply significant predictor the cLBP patients for subjective norm OR (%95CI): 2.095(0.116-2.792), p-value<0.001), intention was significant predictor for perform the PA behavior OR (%95CI): 1.431(0.138-1.538), p-value <0.001), behavior beliefs could predictor for attitude OR (%95CI): 1.276(0.106-1.355), p-value= 0.002). attitude, normative beliefs, subjective norm ,and evaluation outcome behavior could predictors the cLBP patients for intention to perform the PA behavior OR (%95CI): 1.188(0.032-1.312), p-value<0.001)., OR (%95CI): 1.158(0.076-2.208), p-value=0.003) ., OR (%95CI): 1.104(0.076-1.128), p-value<0.001) ., OR (%95CI): 0.814(0.301-1.440), p-value=0.007). Conclusions: This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm). This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm). This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm).

Low back pain (LBP) is a leading cause of disability. It significantly impacts the patient’s quality of life, limits their daily living activities, and reduces work productivity. To reduce the burden of LBP, several pharmacological and non-pharmacological treatment options are available. This review summarizes the role of heat therapy in the management of LBP. First, we outline the common causes of LBP, then discuss the general mechanisms of heat therapy on (LB)P, and finally review the published evidence regarding the impact of heat therapy in patients with acute or chronic non-specific LBP. This review demonstrates that continuous, low-level heat therapy provides pain relief, improves muscular strength, and increases flexibility. Therefore, this effective, safe, easy-to-use, and cost-effective non-pharmacological pain relief option is still relevant in modern clinical practice.

Evaluation of the effects of a high-frequency acceleration (HFA) device on patient pain response to orthodontic forces. A multi-centered trial investigating pain sensitivity to orthodontic forces on 75 subjects at 4 study centers. Subjects underwent clear aligner treatment, with or without adjunctive HFA and documented their pain intensity using the validated NRS10 numeric rating scale. In-Office and At-Home ratings were measured separately for each subject for immediate and extended effect evaluations. Use of HFA devices in conjunction with clear aligner orthodontic treatment demonstrated significant reduction in subjects’ recorded pain ratings vs controls within 5 minutes of aligner exchange, (p = 0.006) and significant reduction in recorded pain ratings vs controls over a 7-day period following aligner exchange (p = 0.018). A 99.6% daily compliance rate with at home use of the HFA device was recorded for all subjects in the study. HFA significantly reduces pain attributed to orthodontic force. HFA delivers clinically significant immediate pain relief, and clinically significant extended pain relief over the 7 days following adjustment.

Cardiovascular disease is the first leading cause of death in the world. Patients with cardiovascular disease may experience various problems, including physiological and psychological problems. Apart from pharmacological therapy, complementary therapy is necessary as a support to conventional medicine. This review aims to describe complementary and alternative therapies for pain and anxiety in patients with cardiovascular disease. This review utilized data from ProQuest, ScienceDirect, and PubMed with search keywords of "Complementary" AND "Nursing" AND "Pain" AND "Anxiety" AND "Coronary artery disease". Ten articles that met the inclusion criteria were analyzed. The results show that nursing actions increasingly develop along with the patient needs. One form of holistic nursing action is complementary and alternative therapy (CAT) that consists of three categories: body-based methods, mind therapies, and sensory therapies. CAT has positive impacts on patients with heart disease. It can reduce anxiety and pain, lower blood pressure, and improve the quality of life. This review also shows that CAT has a positive impact on the recovery of patients with heart disease. Proper therapeutic management should be implemented to reduce the risks of physiological and psychological problems in patients.

With a global estimate of tens of thousands of arachnid enthusiasts, spiders and scorpions are gaining increasing popularity as pets in industrialised countries in Europe, Northern America and Asia. As most spiders and all scorpions are venomous and due to their mostly negative image in the public media, several governments are already considering introducing legislation to regulate the domestic care of potentially dangerous captive animals. We aimed to investigate the circumstances and effects of exposure to arachnids kept in captivity. Thus, we collected and analysed data from 354 self-reported bites and stings attributed to pet arachnids. Our data revealed that on average there were less than 20 recorded envenomations per year with ~90% preventable by due care. We also categorized the severity of the resulting symptoms and found that the vast majority of symptoms were either local (60.7%) or minor (32.8%), 5.4% were asymptomatic, only 1.1% were severe and no fatalities were recorded. Based on our database of bite and sting reports, we performed a risk assessment for arachnid pet ownership and concluded that, with the proper care, arachnids can be safely kept as pets and pose a lower risk than many other recreational activities.

The most common complication of herpes zoster is postherpetic neuralgia (PHN), which is accompanied by severe pain that lowers patients’ quality of life. Although epidural injection of local anesthetics and steroids is effective in controlling neuropathic pain resulting from herpes zoster, few studies report the efficacy and safety of epidural steroid administration in PHN patients. We randomly assigned 42 patients with severe PHN pain (visual analog scale (VAS) score ≥7) to receive continuous epidural infusion of local anesthetics with either a one-time bolus of 5 mg dexamethasone or dexamethasone pulse therapy. VAS scores significantly decreased over time for all patients, but the reduction in VAS scores and likelihood of achieving complete remission were significantly greater among patients who received dexamethasone pulse therapy, without any adverse effects. These results show that continuous epidural infusion of local anesthetics with dexamethasone is effective and safe for reducing PHN pain and promoting complete remission and that more pronounced beneficial effects are associated with more intense epidural steroid administration.

In this paper, the authors seek to discuss some of the complexities involved in cross-cultural working in relation to the communication and management of pain in older people. Specifically, the paper addresses the culture construction of ageing and how pain is often constructed as a natural part of ageing. The authors also suggests that with the rise of the ideology of active-ageing many older people who are disabled or living in chronic pain, may feel a moral imperative to hide pain and ill-health. The discussion extends into looking at the impact of culture and the communication of pain, including specific idioms of distress, somaticize and the lay-management of pain through stoicism.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

This paper is an interdisciplinary study of novel applications of techniques and tools of an area of brain science, known as Synesthesia (involving associations and/or confusion between distinct senses), to area of Computer Science known as Immersive Virtual Reality (VR), that makes the subject’s awareness of physical self be diminished by being surrounded in an engrossing artificial environment. Natural Synesthesia has for the last decade been an important emerging area in brain science but is present in only a small proportion of the population. For example a person with Natural Synesthesia, when viewing a grapheme, may perceive a color additionally to be associated to the grapheme. In contrast, Artificial synesthesia (also known as virtual synesthesia or synthetic synesthesia) has been defined as the sensory joining due a cross-modal mapping device, where information of one sense is accompanied by an induced perception in another sense. In particular, we propose use of a multimodal manner of displaying information in VR to increase and concentrate attention. Artificial Synesthesia to synthetically create induced associations between senses, allowing Artificial Synesthesia to be experienced by anyone using a VR system. The paper describes the enhancement of immersive VR by use of Artificial Synesthesia to improve the system’s performance at steering and directing the attention of the user. We describe techniques for an enhanced immersive VR that displays associations between a variety of senses: between colors and characters, also between colors and sounds, and between sounds and the position of tactile sensations. The sense association provided by Artificial Synesthesia allows the system to better capture the user’s attention and better direct that attention. A major application of our work in VR-induced Artificial Synesthesia is to provide an enhanced methodology for controlling the attention of the subject, and to improve the direction of attention of subjects undergoing guided imagery therapies for pain relief. Other potential high-impact applications include improved immersive VR, more programmable human/computer interfaces and other medical therapies.

Chronic pain is an unpleasant sensory and emotional experience that persists or recurs more than three months and may extend beyond the expected time of healing. Recently nociplastic pain has been introduced as a descriptor of mechanism of pain, which is due to disturbance of neural processing without actual or potential tissue damage, appearing to replace a concept of psychogenic pain. An interdisciplinary task force of the International Association for the Study of Pain (IASP) compiled a systematic classification of clinical conditions associated with chronic pain, which was published in 2018 and will officially come into effect in 2022 in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization. ICD-11 offers the option for recording the presence of psychological or social factors in chronic pain; however, cognitive, emotional, and social dimensions in the pathogenesis of chronic pain are missing. Earlier pain disorder was defined as a condition with chronic pain associated with psychological factors, but it was replaced with somatic symptom disorder with predominant pain in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 2013. Recently clinical nosology is trending toward highlighting neurological pathology of chronic pain, discounting psychological or social factors in the pathogenesis of pain. This review article discusses components of the pain pathway, the component-based mechanisms of pain, central and peripheral sensitization, roles of chronic inflammation, and the involvement of tryptophan-kynurenine pathway metabolites, exploring participations of psychosocial and behavioral factors in central sensitization of diseases progressing into development of chronic pain, comorbid diseases that commonly present a symptom of chronic pain, and psychiatric disorders that manifest chronic pain without obvious actual or potential tissue damage.

Chronic pain is a serious health concern and potentially debilitating condition, leading to anxiety, depression, reduced productivity and functionality, and poor quality of life. This condition can be even more detrimental and incapacitating in the pediatric patient population. In low and middle income countries (LMICs), pain services are inadequate or unavailable, leaving most of the world's pediatric population with chronic pain untreated. Many of these children in LMICs are suffering without treatment, and often die in pain. Awareness and advocacy for this population must be prioritized. We reviewed the available literature on the chronic pediatric pain burden in LMICs, barriers to treatments, and current efforts to treat these patients.

Patients with degenerative diseases refer to feeling more pain during the night. However, it is unknown whether spinal nociception can be circadian and how is it controlled. We investigated whether the paw withdrawal threshold (PWT) could exhibit physiological circadian behavior as well as the contribution of the dopaminergic A11 nucleus and the spinal dopamine (DA) receptors (DRs) on the circadian PWT and the spinal clock gene transcription. Results revealed that control rats present a circadian PWT. Injecting 6-hydroxidopamine (6-OHDA) into the dopaminergic A11 nucleus reduced DA tissue content in the lumbar spinal cord, abolished the circadian PWT, induced allodynia, and reduced Period 1 and 2 (Per1 and 2), retinoid-related orphan receptor α (Rorα), Cryptochrome 1 (Cry1), and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein (Bmal) mRNA. Likewise, administration of D1-like and D2-like DR antagonists blunted circadian PWT, producing allodynia, and altered the clock genes mRNA. In contrast, administration of D1-like or D2-like DR agonists blocked 6-OHDA-induced allodynia. This study shows that the spinal cord has physiological circadian PWT, which is modulated by the descending dopaminergic A11 through differential activation of the spinal DRs. Also, A11 nuclei and spinal DRs can regulate the clock gene transcription, which can likely modulate the circadian PWT.

Lower back musculoskeletal disorders (MSD) are an important public health problem and the leading cause of disability worldwide, but with prevalence yet unknown among shellfish gatherers. To investigate the prevalence and work-related factors associated with lower back MSD in a population of female shellfish gatherers, an epidemiological cross-sectional study was carried out in Saubara, Bahia – Brazil, in 2013. The Brazilian version of the Job Content Questionnaire (JCQ) and the Nordic Musculoskeletal Questionnaire (NMQ), in addition to a questionnaire containing the physical demands adapted to the artisanal work, were applied to a random sample of 209 female shellfish gatherers. The prevalence of lower back MSD was 72.7%. Using multivariate logistic regression, the shellfish gatherers who had worked for more than 26 years in the activity showed a prevalence of 1.22 (95% CI: 1.04-1.44) times higher compared to those unexposed. Lower back MSD was 1.24 (95%CI: 1.08-1.42) times higher among those more exposed to work sitting with trunk flexion. Those performed manual handling and muscle force with the arms had a prevalence ratio of 1.18 (95%CI: 1.01-1.39). These results show the need for greater awareness of health and social welfare factors impacting workers in small-scale fisheries and will promote the elaboration of health care policies for this occupational class.

Modulation of nociception allows animals to prioritise their survival by adapting their behaviour in different contexts. In mammals, this is executed by neurons from the brain, and is referred to as the descending control of nociception. Whether insects have this control, or have the neural circuits underpinning it, has not been clarified. Here, we review evidence supporting descending control of nociception control in insects, and consider which neuronal sub-types and brain areas may be involved.

Major depressive disorder (MDD) is a common mental disorder, which results in seriously impaired condition in the patients and great global disability burden. In light of its quite diverse etiologies, comorbidity with many other diseases, and complex underlying pathology, it has been a great challenge to understand the physiological basis of MDD, which may be a complex of related diseases, rather than a single one. In addition to the partial understanding of MDD, the individual heterogeneities among patients may render the development of a universal treatment an elusive goal. But studying how each of currently available treatments affects the disease can generate useful information to stratify patients into different subtypes for individualized treatments. In this case report, we present the first report of repeated success of using meditation as the only treatment of MDD, compared to initial success but no remission with other conventional antidepressants on the same patient. We hypothesized that the short but continuous natural pain during one-hour meditation sittings has the therapeutic effect to treat depression in the case of this patient and potentially others with MDD. This special opportunity of eliminating tremendous heterogeneity among different individuals has enabled us to probe deeply into the potential mechanism of depression treatments and the complex physiology of depression itself, both of which have likely profound implications in the treatment of other MDD patients as well. More importantly, this case report helps us dissect one specific component of meditation for its long-known and well-established benefit against depression.

Diabetes mellitus is the global epidemic of the 21st century affecting millions worldwide. Usually, patients with long-standing type one diabetes (T1D) or type two diabetes (T2D) tend to develop complications. A common complication is the degenerative of the nerves in the peripheral nervous system (PNS). This complication is known as distal symmetric polyneuropathy or just diabetic neuropathy. A variety of symptoms can be experienced with this complication, including pain and numbness. One characterization of this complication is the sensory loss that begins in the lower extremities and spreads substantially to the fingers and hand. There is no clear mechanism for how this happens in diabetic patients. Studies have shown that nerve damage from this complication can be due to oxidative stress, sorbitol accumulation, and advanced glycation end products (AGEs). Some of the most common medications being provided for diabetic neuropathic pain (DNP) include amitriptyline and desipramine. Other medications also include gabapentin and duloxetine. There are noninvasive options, such as acupuncture, that could provide beneficial data if rigorous studies are conducted. A number of new studies are being completed to identify more effective treatments for this condition.

During prolonged standing, insufficient calf muscle pumping accompanies venous stasis and hypertension in the lower legs, resulting in valve dysfunction, venous wall problems, and subsequent inflammation. Compression therapy, which includes medical compression stockings (MCS) and mechanical intermittent pneumatic compression (IPC), is one of the most effective therapeutic interventions for treating chronic venous diseases. This study aimed to investigate the safety and efficacy of IPC and MCS, and the optimal protocol of compression therapy for chronic venous disease. This crossover trial was conducted for healthy, long standing workers (>8 h daily) with leg edema and pain. Four groups were established for each visit: group A (resting after work without MCS), group B (resting after work with MCS), group C (IPC after work without MCS), and group D (IPC after work with MCS). The primary outcome was the visual analogue scale (VAS) score for leg pain. The secondary outcomes were leg volume (mL), circumference (cm), extracellular fluid/total body fluid (ECF/TBF), and extracellular water/total body water (ECW/TBW) through bioimpedance analysis. Outcomes were assessed before work (T0), after work (T1), and 60 minutes after intervention (T2). We included 39 healthy volunteers, aged 30.03±7.56 years. All four groups had significantly increased leg pain after work (T0-1) but improved 60 minutes after intervention (T1-2), particularly group C (decreased VAS by 1.9). When leg swelling was compared at T0 and T1, groups A and C showed significant increases in leg volume and circumference, indicating significant work-induced edema, whereas groups B and D showed no change or even a decrease. After interventions, leg volume and circumference significantly decreased in groups A and C, although groups B and C did not show significant improvement. The ECF/TBF and ECW/TBW of all groups decreased after interventions. Leg pain and edema after prolonged standing in healthy adults were safely and effectively improved by IPC. Although MCS also reduced leg edema immediately after work, it did not show significant improvement in leg pain at T0-1–and T1-2, nor in swelling at T1-2.

(1) Background: Although manual therapy for pain relief has been used as an adjunct in treatments for chronic low back pain (CLBP), there is still the belief that a single session of myofascial release would be effective. This study aimed to investigate whether a single session of a specific technique reduces pain and disability. (2) Methods: This was a crossover clinical trial in which 41 participants over 18 years old with CLBP were randomly enrolled into 3 situations - experimental, placebo, control, in a balanced and cross-over manner. The subjects underwent a single session of myofascial release on thoracolumbar fascia and compare it with the control and placebo. Outcome were pain and functionality, evaluated using the numerical pain rating scale (NPRS), pressure pain threshold (PPT) and Oswestry (ODI). (3) Results: There was no effects between-, within-tests, and interaction for all the outcomes, i.e., NPRS (η 2 = 0.32, F = 0.48, p = 0.61), PPT (η2 = 0.73, F = 2.80, p = 0.06), ODI (η 2 = 0.02, F = 0.02, p = 0.97). (4) Conclusion: A single trial of thoracolumbar myofascial release technique was not enough to reduce pain and disability in subjects with CLBP.

Low Back Pain (LBP) is one of the most common problems among adults. The usual physiotherapy treatment is to perform physical exercises. However, some LBP patients have false beliefs regarding their pain and they tend to avoid physical movements which might increase their pain and disability. Virtual Reality (VR) has shown to be an effective intervention in improving motor functions and reducing pain perception. Existing VR interventions for LBP rehabilitation were based on a non-immersive VR, whereas to effectively reduce the pain intensity, we need an immersive VR. In this paper, we introduce the development and evaluation of a serious game called RabbitRun with an immersive experience to engage the patients in a virtual environment and distract them from the pain while performing LBP exercises. The initial usability evaluation results suggest that RabbitRun game is enjoyable and acceptable. The game is easy to play and learn and most of the participants are willing to play the game at home. This solution will enhance the rehabilitation outcome since the patients who are suffering from LBP can use the system at their home and train more for long period of time using a smartphone and low-cost virtual reality device such as Google Cardboard.

The traditional standards employed for pain assessment have many limitations. One such limitation is reliability because of inter-observer variability. Therefore, there have been many approaches to automate the task of pain recognition. Recently, deep-learning methods have appeared to solve many challenges, such as feature selection and cases with a small number of data sets. This study provides a systematic review of pain-recognition systems that are based on deep-learning models for the last two years only. Furthermore, it presents the major deep-learning methods that were used in review papers. Finally, it provides a discussion of the challenges and open issues.

Rationale:First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrates modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.Patient Concerns:This case describes a 63-year-old male who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line poly-pharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.Diagnosis:Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction (MI). He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow up and, despite medical management over the past 6 years, his UA became progressively debilitating.Interventions and Outcomes:In conjunction with his standard cardiac care, patient had a gradual lessening of UA related pain, including frequency and character, after using an edible form of medical cannabis (MC) (1:1 CBD:THC). Following continued treatment, he ceased long term morphine treatment and describes the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.Lessons:This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA; while concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.

Feeling pain means feeling oneself, as the body feels discomfort as a kind of "disturbance experi-ence". Endometriosis is a disease in which the predominant symptom is pain felt by women pri-marily within the pelvis, but also outside of the body. The clinical biomarker used in the diagnosis of this disease is microRNAs. Treatment of endometriosis is complex and is based mainly on phar-macotherapy. Physiotherapy can complement pharmacological treatment in reducing pain using non-invasive treatments for the body. Therefore, databases have been searched to find the most effective forms of physiotherapy for the treatment of endometriosis. The literature review conducted here suggests that it is necessary to perform multicentre studies in order to establish which forms of physical therapy may be most effective in reducing pain and improving the quality of life of women suffering from endometriosis. Certainly, this type of research in conjunction with the assessment of pain and endometriosis markers would be of great clinical value in order to develop an interdisci-plinary treatment model.

Pharmacological treatment is not very effective for neuropathic pain (NP). A progressive decrease in the estimated effect of NP drugs has been reported, giving rise to an increase in the use of the multimodal analgesic approach. We performed a new, independent review to assess whether more evidence and of better-quality has become available since the last systematic review. We evaluated the efficacy, tolerability, and safety of double-blinded, randomized, controlled trials involving only adult participants and comparing combination therapy (CT: ≥ 2 drugs) to a placebo and/or at least one other comparator with an NP indication. The primary outcome assessed was the proportion of participants reporting ≥50% pain reductions from baseline. The secondary outcome assessed was the proportion of drop-outs due to treatment-emergent adverse events. After removing duplicates, 2323 citations were screened, with 164 articles assessed for eligibility, from which 16 were included for qualitative analysis. From the latter, only five lasted for at least 12 weeks and only six complied with the required data for complete analysis. CT has been adopted for years without robust evidence. Efforts have been made to achieve better-quality evidence, but the quality has not improved over the years. In this regard, guidelines for NP should attempt to make recommendations about CT research, prioritizing which combinations to analyze.

Background: Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1(TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Methods: Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG island in the TRPA1 gene were examined using whole blood. Results: Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 also significantly increased together with increase in DN4 scores. Conclusions: Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.

Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary palliative care

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

Central nervous system (CNS) uses vision, vestibular, and somatosensory information to maintain body stability. Research has shown that there is more lumbar proprioception error among low back pain (LBP) individuals as compared to healthy people. In this study, two groups of 20 healthy people and 20 non-specific low back pain participants (LBP) took part in this investigation. This investigation focused on somatosensory sensors and in order to alter proprioception, a vibrator (frequency of 70Hz, amplitude of 0.5 mm) was placed on the soleus muscle area of each leg and two vibrators were placed bilaterally across the lower back muscles. Individuals, whose vision was occluded, were placed on two surfaces (foam and rigid) on force plate, and trunk angles were recorded simultaneously. Tests were performed in 8 separate trials; the independent variables were vibration (4 levels) and surface (2 levels) for within subjects and 2 groups (healthy and LBP) for between subjects (4×2×2). MANOVA and multi-factor ANOVA tests were done. Linear parameters for center of pressure (COP) (deviation of amplitude, deviation of velocity, phase plane portrait (PPP), and overall mean velocity) and nonlinear parameters for COP and trunk angle ((recurrence quantification analysis) RQA and Lyapunov exponents) were chosen as dependent variables. Results indicated that NSLBP individuals relied more on ankle proprioception for postural stability. Similarly, RQA parameters for the COP on both sides and for the trunk sagittal angle indicated more repeated patterns of movement among the LBP cohort. Analysis of short and long Lyapunov exponents showed that people with LBP caused no use of all joints in their bodies (non-flexible), are less stable than healthy subjects.

Abstract: This study evaluates the effect of paravertebral spinal injection (PSI), utilizing both subjective and objective assessments in chronic low back pain (LBP) associated with facet joint arthrosis over a one-month duration. Subjective questionnaires included the Visual Analogue Scale (VAS) for pain, Oswestry Disability Index, Health Survey SF-12, and the short Falls Efficacy Scale International (FES-I). Objective assessments included in-clinic gait and timed-up-and-go (TUG) tests using wearable sensors, as well as 48-hour daily physical activity (DPA) monitored using a chest-worn tri-axial accelerometer. Subjective and objective measures were performed prior to treatment, immediately after the treatment, and one-month afterthe treatment. Eight LBP patients were recruited for this study (mean age = 54±13 years, body mass index = 31.41±6.52 kg/m2, 50% males). Results show significant decrease in pain (~55%, p<0.05) and disability (Oswestry scores, ~21%, p<0.05). In-clinic gait and TUG were also significantly improved (~16% and ~18% faster walking and shorter TUG, p<0.05); however, DPA (including percentage of physical activities (walking and standing) and the number of steps) showed no significant change after PSI (p>0.25; effect size≤0.44). We hypothesize that DPA may continue to be truncated by conditioned fear-avoidance, a psychological state that may prevent increase in daily physical activity to avoid pain.

7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural origin (Tussilago farfara)has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. Neuropathic pain was induced in mice by PSNL surgery performed on day 1 and ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose dependent manner. ECN significantly reversed the severity of neuropathic pain by improving distress symptoms and survival rate. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, anti-neuropathic potential of ECN might be due to inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

Lower Back Pain (LBP) is a disease that needs immediate attention. Person with back pain shall go immediately to doctor for treatment. Injury, excessive works and some medical conditions are result of back pain. Back pain is common to any age of human for different reasons. Due to factors such as previous occupation and degenerative disk disease the chance of developing lower back pain increases for older people. It hampers the working condition of people common reason for seeking medical treatment. The result is absence from work and is unable to normal due to pain. It creates uncomfortable and debilitating situations. Hence, detecting this disease at an early stage will assist the medical field experts to suggest counter measures to the patients. Detection of lower back pain is implemented in this paper by applying ensemble machine learning technique. This paper proposes Stacking ensemble classifier as an automated tool that will predict lower back pain tendency of a patient. Experimental result implies that the proposed method reaches an accuracy of 76.34%, f1-score of 0.76 and MSE of 0.34.

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute pain conditions like post-operative and post-traumatic pain. Besides that, and despite the very satisfactory results achieved by oral analgesics, parenteral analgesia is a key tool in the treatment of painful conditions when the enteral routes are not convenient. The parenteral ready-to-use fixed-dose combinations of NSAIDs with non-opioid analgesics like paracetamol or metamizole could play a central role in the treatment of painful conditions since they are able to gather into only one formulation the advantages of multimodal and parenteral analgesia. Surprisingly, only very recently a parenteral ready-to-use fixed-dose combination of Ibuprofen/Paracetamol was launched to the market. This review aims to review the current availability of NSAID-based Parenteral Fixed-dose combinations with paracetamol and metamizole in the European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, it is explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. With this review, we concluded that, despite the well-recognized utility of combining NSAIDs with non-opioid analgesics, there are in the literature several randomized clinical trial studies unable to demonstrate clear advantages concerning their efficacy and safety. In the future, it is deemed necessary to perform clinical trials specifically designed to assess the efficacy and safety of these fixed-dose formulations to generate solid evidence of their clinical advantages.

Background: Objectives. The objective of this study was to compare the efficacy of direct current stimulation (DCS) applied at the transcranial, suboccipital and spinal level on experimental sensory modalities and pain outcome measures in healthy subjects. The hypothesis of this study was that systematic analysis of the efficacy of DCS on modulating evoked thermal and mechanical pain modalities and mechanisms such as endogenous pain modulation in healthy individuals would reveal sensitive outcome measures help develop this technique for the control of chronic pain. Materials and Methods. Database searches were conducted up to December 2019 for randomized controlled trials that performed sham-controlled DCS of experimental sensory modalities and pain outcomes following transcranial, suboccipital and spinal locations in healthy participants. Standardized mean differences with 95% confidence intervals were calculated for sensory modalities, including random-effect metanalysis. Results: Thirty-one studies were included for analysis (647 participants). A significant decrease in pain intensity for active vs sham transcranial stimulation was identified for pain intensity (n=158; SMD=0.79; 95% CI=0.56 to 1.02), a significant increase in heat pain threshold (n=222; SMD=1.16; 95% CI=0.95 to 1.37), and a significant increase in cold pain threshold (n = 155; SMD = 0.77, 95% CI 0.53 to 1.01). No significant modulation of pressure pain threshold was identified with DCS and only a limited number of studies focused on experimental pain modulation following neuromodulation at the suboccipital or spinal level. Conclusions: These results show significant transcranial DCS neuromodulation of pain intensity and on thermal pain modalities. Future studies should focus on endogenous pain and sensory modality modulation with sham-controlled DCS applied at transcranial, suboccipital and spinal locations.

Low back pain is a common problem in the active population, and the second reason for visiting a physician. In patients with lumbar disc protrusion, the nucleus pulposus bulges against the disc and the latter protrudes into the spinal column, but the annulus fibrosus remains intact. The purpose of this study was to prove that starting an early complex rehabilitation treatment results into pain and disability reduction, and increased muscle strength and mobility in patients with lumbar disc protrusions. We performed a prospective cohort study, enrolling 60 patients (25 men and 35 women) aged between 26 to 76 years, diagnosed with lumbar disc protrusion. Patients in the experimental group registered significant improvements in all studied variables (pain, mobility, muscle strength, disability) after 6 months of treatment. The results of our study suggest that, in the lumbar disc disease, a combined rehabilitation program may be more effective in terms of pain and disability reduction, if it starts early after diagnosis. The current study proves the importance of combining electrotherapy with hydrotherapy and physical therapy. Patients who received this treatment combination showed an extremely significant improvement in pain relief, and reduction of functional disability after 6 months of treatment.

Objectives: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given 0.9% NaCl by oral gavage while low-dose, medium-dose, and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behavior of mice were analyzed for each group. Hematoxylin and eosin staining were used to investigate prostate inflammation. The serum level of tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. Key findings: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. Conclusions: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analyzing clinically relevant symptoms (urinary tract system, pelvic pain, and prostate inflammation), and preliminary explored the inflammatory-related treatment mechanisms by measuring TNF-α.

Background Children often suffer the nonspecific musculosceletal pain as reported in literature. Aim To determine relationship between body weights with development of musculoskeletal pain and to determine whether growing in body height is associated with musculoskeletal pain in schoolchildren. Subjects/ Methods A prospective longitudinal study included 1315 school children aged 7-14 years (652 boys and 663 girls) and was performed in 13 elementary schools in B&H. Child body height and body weight were measured. The survey of perception of musculoskeletal pain in different body regions of subjects was conducted by adjusted Nordic Musculosceletal Questionnaire (NMQ). Results The highest prevalence of an overweight and obesity in the 10th year 35.7% and the lowest frequency 17.8% in the 14th year was. In the age 14th obesity was’nt found. Boys have more prevalence of overweight. Using logistic regression model, we found that school children with normal BMI were protected with increased body height of acute lower back pain (β= -0.089, 95%CI, -9.730- -0.023, P< 0.049), and increased body height was protector of obese school children of acute upper back pain (β= -0.356, 95%CI, -14.077- -3.878, P< 0.001) and chronic lower back pain (β= -0.356, 95%CI, -14.077- -3.878, P< 0.001). Conclusion Schoolchildren with normal weight more often have had musculosceletal pain than those with overweight or obesity. This can be associated with intense physical growth period in height, especially. The assumption is that the increase in height changes the relationship between excessive BMI and musculoskeletal pain in children of school age.

When we are asleep we lose the ability to promptly respond to external stimuli and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways, we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to which extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

The study of pain requires a balance between subjective methods that rely on self-reports and complementary objective biometrics that ascertain physical signals associated with subjective accounts. There are at present no objective scales that enable the personalized assessment of pain, as most work involving electrophysiology rely on summary statistics from a priori theoretical population assumptions. Along these lines, recent work has provided evidence of differences in pain sensations between participants with Sensory Over Responsivity (SOR) and controls. While these analyses are useful to understand pain across groups, there remains a need to quantify individual differences more precisely in a personalized manner. Here we offer new methods to characterize pain using the moment-by-moment standardized fluctuations in EEG brain activity centrally reflecting the person’s experiencing temperature-based stimulation at the periphery. This type of gross data is often disregarded as noise, yet here we show its utility to characterize the lingering sensation of discomfort raising to the level of pain, individually, for each participant. We show fundamental differences between the SOR group in relation to controls and provide an objective account of pain congruent with the subjective self-reported data. This offers the potential to build a standardized scale useful to profile pain levels in a personalized manner across the general population.

Background We intend to examine whether the COVID-19 outbreak influences medical decision-making (MDM) among Non-COVID patients. Method We recruit 287 patients who admit to ER department due to cardiovascular complaints. Anxiety level was measured using three questionnaires (GAD-7, Beck Inventory, and the cardiac anxiety questionnaire). A fourth survey was designed to assess MDM considerations. Results 64% of patients were male (median age 54). Almost half of the patients were found to have moderate to severe levels of anxiety.79.3% of patients reported that the outbreak influenced their MDM. 44.5% of patients sought medical care 2-3 from the onset of symptoms. Coronary artery disease was found in only 26 patients (9.1%). Almost half of the patients stated that they would have gone earlier if not for the current pandemic. Conclusion Non-COVID patients seeking medical care had a high anxiety level that directly affected decision-making and put them at unnecessary risk.

The aim of the following paper was to determine the influence of soft tissue therapy on respiratory efficiency and chest mobility of women suffering from breast cancer. This study was a controlled randomized trial. Tests were carried out in a group of patients (n=49), who were hospitalized in the Province Polyclinic Hospital, Konin, Poland. In the study group, irrespective of the standard physical therapy program, an additional therapy program was run. The program consisted in applying specific techniques of soft tissue treatment. All patients in the each term were subject to pulmonary function test, chest mobility and pain assessment. Statistical analysis of the obtained results of spirometry and chest mobility assessment have revealed no differences in the analyzed parameters between the examined groups in the period of joint therapeutic treatment. In the period between the 3rd examination and the end of the 11-month- rehabilitation treatment, statistically significant differences were observed in the analyzed spirometry parameters, however, there was no difference in the parameters describing airflow in small airways (MEF₅₀,PEF) between individual groups, during consecutive examinations in the course of diversified therapeutic treatment. Chest mobility assessment of the patients, performed during diversified therapeutic treatment, revealed statistically significant differences between the groups. However, there was no difference between the examined groups, as far as pain sensation is concerned. Enhancing the regular rehabilitation program by including additional therapeutic methods, which are based on myofascial release and post-isometric relaxation techniques, had a beneficial effects regarding respiratory system efficiency.

Abstract Background: Chronic pain is common among older adults and is associated with adverse physical and psychological outcomes. Given the expected burden and limited healthcare resources, an innovative and cost-effective method to manage chronic pain should be developed. Peer volunteers (PVs) have been used as an affordable alternative to professional services to help patients manage their chronic conditions including pain with success and acceptance. The aim of this paper is to explore the experiences and perceptions of PVs in a peer-led pain management program among nursing home residents. Methods: This longitudinal study formed part of a wider research study, a clustered randomised controlled trial, which investigates the effectiveness of a 12-week peer-led pain management program (PAP) in relieving chronic pain and enhancing pain self-efficacy among nursing home residents. Quantitative data were collected from questionnaires (demographics, pain situation and pain knowledge) for all PVs. Qualitative data (PVs’ experiences in leading the PAP, their perceived benefits, limitations and barriers encountered, its usefulness to the participants and recommendations for improving the PAP) were collected from focus group for a selected sample at baseline (before attending the training) and at week 12 (upon completion of the PAP). Data were analysed using the Statistical Package for Social Sciences and NVivo 8. Results: A total of 46 PVs were recruited (34 female, 74%), with mean±SD age of 61.0±5.1 years. Thirty-one PVs reported to have chronic pain. Before the training, self-rated pain knowledge was 39.1±20.4 (maximum 100 points). When actual pain knowledge was assessed, a mean pain knowledge score of 86.1±10.6 points was found. There was a significant difference between the self-rated pain knowledge and the pain knowledge score (p<0.001). PVs reported to have improvement in their knowledge and skills. No PVs reported negative comments regarding their role in the PAP, although experienced barriers such as communication, space and privacy were reported. Conclusions: This study provides further evidence that peer-led pain management program is feasible. Barriers identified may benefit the design and planning of future PAP. Trial registration: ClincalTrials.gov (NCT03823495), 30 January 2019. (Retrospectively registered).

As neck and/or shoulder pain (NSP) frequently occur together with tension-type headache (TTH) and migraine, we explored how concomitant NSP affects perceived treatment responses to an analgesic. An anonymous survey was performed among 895 TTH and migraine sufferers who used the analgesic 400 mg ibuprofen/100 mg caffeine. NSP was relatively abundant among patients (42.4% for TTH; 39.2% for migraine), and associated with &gt;1 additional day with headache per month. Reported pain reduction was independent from NSP for TTH and migraine. More patients became pain-free at 2 h in migraine with NSP (42.9%) compared to migraine without NSP (32.2%), which is different from TTH with NSP (60.6%) and TTH without NSP (71.4%). For both, migraine and TTH, a recurrence of headache on the same day was more prevalent in those with concomitant NSP leading to a greater likelihood of taking a second dose of the analgesic. NSP frequently occurs together with TTH and migraine patients. In migraine, NSP seems to be associated with a better treatment response at 2 h. The more frequent recurrence of pain in those with concomitant NSP indicates that NSP makes both headache types worse. Further studies are needed to substantiate these effects.

Although the majority of mobile phone (MP) users do not attribute adverse effects on health or well-being to MP-emitted radiofrequency (RF) electromagnetic fields (EMFs), the exponential increase in the number of RF devices necessitates continuing research aimed at the objective investigation of such concerns. In this work, we investigate the effects of acute exposure from Long Term Evolution (LTE) MP EMFs on thermal pain threshold in healthy young adults. We use a protocol that was validated in a previous study in a capsaicin-induced hyperalgesia model, and was also successfully used to show that exposure from an RF source mimicking a Universal Mobile Telecommunications System (UMTS) MP led to mildly stronger desensitization to repeated noxious thermal stimulation relative to the sham condition. Using the same experimental design, we did not find any effects of LTE exposure on thermal pain threshold. The present results are in accordance with previous evidence suggesting that effects are likely to be placebo/nocebo effects and are unrelated to the brief acute LTE EMF exposure itself. The fact that this is dissimilar to our previous results on UMTS exposure implies that RF modulations might differentially affect pain perception, and points to the necessity of further research in the topic.

Thoracotomy is one of the most painful types of incision a patient can experience. Pain is a very complex pathophysiological entity. Neuronal pathophysiological mechanisms are integrated with the immunological response, which amplify inflammation and pain. Prolonged inflammation induces a pathological response of the immune-system and constantly stimulate the nociceptive pathways generating chronic pain. The mechanisms are particularly altered in lymphomas, where pain following chest surgery often becomes chronic and reduces the quality of life. In this study 51 elderly patients who had undergone a transthoracic biopsy to verify the suspect of mediastinal lymphoma were examined for pain reduction with oral opioids, effect of epidural analgesia and paravertebral block. Subsequently, patients underwent tensed torsion exercises, progressively intensified. After the first few days, patients walked progressively for 20 minutes a day. Once discharged a program of patients started aerobic exercises to increase muscle endurance and to strengthen the extensor muscles of the legs and of the upper limbs. The systemic administration of opioids is the simplest and most common method of providing analgesia for postoperative pain, but early mobilization, respiratory rehabilitation, and muscle toning exercises are excellent support devices both for physical and psychological recovery.

According to the literature, patients with chronic pain and mental disorders constitute a huge, heterogeneous group. However, it is known that social and psychological processes closely affect the level and expression of chronic pain. In this paper, we present a review of the literature, define methods of identifying pain biomarkers and consider the possibility of using them to assess pain in mental disorders. Group researchers searched PubMed, Scope, and Cochrane databases for "pain biomarkers in mental disorders" between 2011 and 2021. for available databases for full-text, peer-reviewed studies and review publications using the following keywords: pain biomarkers, neuroimaging pain, pain metabolomics, pain and psychiatric disorders, pain electroencephalography (EEG), serum pain biomarkers, saliva biomarkers, and diagnosis pain. The search included full-text articles, clinical trials, randomized controlled trials, and systematic reviews. Was used part of the PRISMA method to review the literature systematically. A literature search identified 283 studies based on the initially set inclusion and exclusion criteria. In the subsequent selection stages, 11 studies were selected for analysis. There are three main areas of the possible use of biomarkers for the clinical assessment of pain in psychiatric patients, neuroimaging, changes in metabolite levels in body fluids, and changes in gene expression. As a result of the review, individual pain mediators were distinguished that may be markers of pain in psychiatric patients. Some mediators indicate the specificity of pain and are of diagnostic importance. However, despite significant advances in research, most of the described biomarkers found in clinical trials assessing the severity and frequency of pain have no practical significance in psychiatric disorders. It is possible to diagnose pain based on neuroimaging using various methods, genetic methods, body fluids: blood and urine. Of the many, body fluid biomarkers are the most advanced. Discussion: Biomarker research is a dynamically developing field. The review has proposed new ways to diagnose pain by identifying pain biomarkers. Work presented pain diagnostics in psychiatric disorders based on biomarkers from various neuroimaging methods, blood and urine analysis. The possibility of new, effective techniques gives hope for the correct diagnosis of pain, especially in patients with mental disorders, which would allow for appropriate and adequate therapeutic therapies. In clinical practice is limited to a few methods. Assessment of pain biomarkers in body fluids (serum, saliva, and urine) seems to be the most practical and promising method of clinical application. Conclusions: There are new techniques that give hope for the correct diagnosis of pain, especially in patients with mental disorders, which will allow for their proper and adequate therapy. According to the literature, patients with chronic pain and mental disorders constitute a huge, heterogeneous group. However, it is known that social and psychological processes closely affect the level and expression of chronic pain.

Migraine is a primary headache disorder with a prevalence of 11.6% globally and 27% in Saudi Arabia. Irritable bowel syndrome has a prevalence of 9.2% worldwide. The prevalence of IBS has not been established nationally. However, provincial studies for both migraine and IBS have been conducted across the nation. There is a significant link between migraines and IBS globally. This identifies an association that needs to be investigated in a nationwide manner. This study aims to observe the association and the relationship between migraine and irritable bowel syndrome in Saudi Arabia. A cross-sectional study was conducted between March 2021 to June 2021 among the general population of Saudi Arabia, whose ages are 15 years old or greater. The data collection tools included MS-Q for migraine symptoms, MIGSEV scale for severity of migraine, and The IBS module of the Rome IV Diagnostic Questionnaire (R4DQ) for IBS symptoms and its subtype. With a total of 2802 participants, the majority of the study sample were males, who constituted 52.5%. Among the study's sample, the prevalence of migraine consisted of 27.4%, and the prevalence of IBS was 16.4%. The odds of having IBS in migraineurs were much higher than in those without migraines (OR 4.127; 95% CI 3.325-5.121), and the association was statistically significant (P&lt;0.001). In conclusion, there is a strong association between migraine and irritable bowel syndrome in Saudi Arabia.

We describe a recently developed approach to quantify welfare loss in animals, the Cumulative Pain metric. It combines the two most relevant dimensions of negative affective experiences: intensity and duration. The metric enables estimating the time individuals spend in negative affective states of a physical or psychological nature (operationally referred to simply as ‘pain’) of different intensities as the result of one or more challenges (e.g., diseases, injuries, deprivations). A new notation protocol (the Pain-Track) is used in which the duration of the experience is represented along the horizontal axis and intensity is represented by four categories in the vertical axis. Pain experiences are partitioned into temporal segments, where hypotheses for the experienced duration and intensity are proposed based on existing welfare indicators (e.g., neurophysiological, behavioral, anatomical, evolutionary). This structure forces transparency about assumptions and uncertainties, highlights knowledge gaps, and enables estimates to be continuously adjusted. Because the Cumulative Pain metric is based on parameters with a broadly common biological meaning, it provides the much needed interoperability among assessments of animal welfare. It enables comparing the impact of practices and living conditions, policies and interventions, and the calculation of welfare footprints of animal-sourced products using a universal measurement unit.

Suicidal behaviour is a public health problem whose magnitude is both substantial and increasing. Since many individuals seek medical treatment following a suicide attempt, strategies aimed at reducing further attempts in this population are a valid and feasible secondary prevention approach. An evaluation of the available evidence suggests that existing treatment approaches have limited efficacy in this setting, highlighting the need for innovative approaches to suicide prevention. Existing research on the neurobiology of social pain has highlighted the importance of this phenomenon as a risk factor for suicide, and has also yielded several attractive targets for pharmacological preventive strategies. In this paper, the available evidence related to these targets is synthesized and critically evaluated. The way in which social pain is related to the “anti-suicidal” properties of recently approved treatments, such as ketamine and psilocybin, is also examined. Such strategies may be effective for the short-term reduction of suicidal ideation and behaviour in individuals who have made a suicide attempt suicide prevention, particularly in cases where social pain is identified as a contributory factor. These pharmacological approaches may be effective regardless of the presence or absence of a specific psychiatric diagnosis.

This study presents three forms of interdisciplinary expertise in the healthcare design context to approach a particular multifaceted problem around the current healthcare for older adult patients with chronic low-back pain (LBP). Using an interdisciplinary co-design framework, first, our design approach performs the role of an initiator to define the problem by exploring the current context of healthcare. Second, it facilitates the experiences of experts and patients to reach the roots of the problem by functioning as a mediator. Third, our approach fulfills the primary role of healthcare design in producing new meanings considering the principles of patient-centeredness. These roles significantly contributed to the design of healthcare innovations. Our framework transformed the distributed disciplinary knowledge developed while tackling the multifaceted problem into new forms of expertise for collaboration in healthcare innovation.

Isolated fallopian tube torsions presenting to the emergency department are a very rare cause of childhood acute abdominal pain. Since the diagnosis to be made in the early period is of importance in terms of affecting tubal damage and fertility, it was aimed to evaluate the cases in the light of literature. Materials and Methods: This study included 10 patients under 18 years of age presented to the emergency department with abdominal pain between January 2003 and December 2018. The mean age was 14.5±1.43 years (range: 12-17years). The demographic characteristics, surgical findings, and methods, concomitant pathology results of these patients were retrospectively evaluated. Results: The reason for admitting to the emergency department of 10 patients included in the study was abdominal pain. The mean duration of hospital admission with pain was 4.97 days. The onset of pain was less than 24 hours in 7 patients (70%) and was more than 24 hours in three patients (30%). Of the patients, 9 (90%) had tenderness in the lower abdominal quadrant, 5 (5%) had the defense, and 3 (30%) had a rebound. Nausea, vomiting, and leucocytosis were present in 50% of the cases. Right and left tubal involvement of the cases was equal. Seven (70%) of the isolated tubal torsions were accompanied by paraovarian cysts. Of the patients, 8 (80%) underwent open surgery and 2 (20%) underwent laparoscopic intervention. Detorsion was performed in 5 (50%) and salpingectomy was performed in 5 (50%) cases. Conclusion: Isolated tubal torsion should be considered in children presenting with acute abdominal pain in early adolescence. Early diagnosis is important for the maintenance of fertility.

Objectives: This study aimed to investigate and compare sleep quality between patients with chronic temporomandibular disorder and healthy controls, and to analyze the association of sleep quality with disease characteristics, obstructive sleep apnea risk factors, and excessive daytime sleepiness. Methods: Chronic temporomandibular disorder patients (n=503) and 180 age- and sex-matched healthy controls were included, who completed well-organized clinical report and answered questions on sleep quality (Pittsburgh Sleep Quality Index), sleep apnea risk factors (STOP-Bang questionnaire), and excessive daytime sleepiness (Epworth sleepiness scale). Results: Mean global Pittsburgh Sleep Quality Index scores were significantly higher in the patients (6.25±2.77) than in healthy controls (6.25±2.77) (p&lt;0.001). Poor sleep was significantly more prevalent in the patient group (56.9%) than in healthy controls (22.2%) (p&lt;0.001). Compared with healthy controls, chronic temporomandibular disorder patients had a higher likelihood of obstructive sleep apnea. (STOP-Bang total score ≥3; 7.2% vs. 16.1%; p&lt;0.01) and higher excessive daytime sleepiness (Epworth sleepiness scale score ≥10; 12.8% vs. 19.7%; p&lt;0.05). Age (odds ratio=2.551; p&lt;0.001), female sex (odds ratio=1.885; p=0.007), total Epworth sleepiness scale score (odds ratio=1.839; p=0.014), and headache attributed to temporomandibular disorder (odds ratio=1.519; p=0.049) were the most powerful predictors of poor sleep (global Pittsburgh Sleep Quality Index score ≥5) in chronic temporomandibular disorder patients. Conclusion: Chronic temporomandibular disorder patients had sleep quality impairment. Various factors, including peripheral and central factors, affect the patient's sleep quality. Therefore, in addition to sleep quality and sleep-related problems, the underlying central mechanism for poor sleep quality should be assessed when treating chronic temporomandibular disorder patients.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a dose reduction of chemo-therapy and its most common sensory symptoms are severe pain, tingling, and numbness in the hands and feet. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory abnormalities may occur for months, or even years after the termination of chemotherapy. This disease has complicated pathophysiology featured by underlying mechanisms not completely known. Although many pharmaco-logical and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized cure to prevent or treat CIPN. According to current guidelines, Duloxe-tine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective thera-pies for CIPN is mandatory. The purpose of this review is to dissect CIPN, the target and immunothera-py-based approaches to this disorder, as well as to offer new insights for novel therapeutic perspectives.

Children and adolescents with severe burns require dressing changes, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic reviewsearch resulted in eight studies and 142 patients. This exercise included quality and risk of bias assessment. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (SMD=0.94; 95% CI=0.62, 1.27; Z=5.70; p&lt;0.00001) for adjuvant full immersive VR compared to standard care. In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with burns. We therefore recommend implementing full immersive VR as an adjuvant in this specific setting and population. However, this requires further research into the hygienic use of VR appliances in health institutions. Furthermore, due to the high cost of the hardware, a cost-benefit analysis is required. Finally, research should also verify the long term physical and psychological benefits of VR.

Nociceptive innervation of the thoracolumbar fascia (TLF) has been investigated over decades, however these studies have not been compiled or collectively appraised. The purpose of this scoping review was to assess current knowledge regarding nociceptive innervation of the TLF to better inform future mechanistic and clinical TLF research targeting low back pain (LBP) treatment. PubMed, ScienceDirect, Cochrane and Embase databases were searched in January 2021 using relevant descriptors encompassing fascia and pain. Eligible studies were: (a) published in English; (b) preclinical and clinical (in vivo and ex vivo) studies; (c) original data; (d) included quantification of at least one TLF nociceptive component. Two-phase screening procedures were conducted by a pair of independent reviewers, data were extracted and summarized from eligible studies. The search resulted in 257 articles of which 10 met inclusion criteria. Studies showed histological evidence of nociceptive nerve fibers terminating in low back fascia, suggesting a TLF contribution to LBP. Noxious chemical injection or electrical stimulation into fascia resulted in longer pain duration and higher pain intensities than injections into subcutaneous tissue or muscle. Pre-clinical and clinical research provides histological and functional evidence of nociceptive innervation of TLF. Greater knowledge of fascial neurological components could impact LBP treatment.

Back pain is a common symptom that affects all age groups across the globe, when left untreated may eventually lead to disability. A convenient sample selection method was used in this study due to the global Covid-19 pandemic lockdown which was effective in Turkey during the investigation period. Thus, virtual data collection and health education including some health risks were employed. A total population of two hundred adult women was involved in the study but one hundred and twenty-one responses were collected. Findings show that, for socio-demographic characteristics, the pain was found highest in women between the ages of 41-50 and obese/overweight individuals. Although, there was no significant difference recorded in the marital status category. Moreover, statistical mean differences were detected between the scales for ODI (4.18) and BPFS (6.09). Also, p<0.05, paired sample t-test was 0.001 ODI and 0.001 BPFS after the training exercise. This suggests that exercise training is inversely correlated with pain severity which implies that training has a significant influence on pain intensity. Thus, it could be concluded that there is a relationship between the training exercise and ODI/BPFS.

Neuroscience is a vast discipline that deals with the anatomy, biochemistry, molecular biology, physiology and pathophysiology of central and peripheral nerves. Advances made through basic, translational, and clinical research in the field of neuroscience have great potential for long-lasting and beneficial impacts on human health. The emerging field of biological therapy is intersecting with the disciplines of neuroscience and rheumatology, creating new horizons for interdisciplinary and applied research. Biological drugs, growth factors, neuropeptides and monoclonal antibodies are being developed and tested for the treatment of painful arthritic and rheumatic diseases. This concise communication focuses on the solutions provided by the fields of neuroscience and neuroimmunology for real-world clinical problems in the field of rheumatology, focusing on synovial joint pain and the emerging biological treatments that specifically target pathways implicated in osteoarthritis pain in peripheral nerves.

Cannabis has been used as an herbal remedy for thousands of years and recent research indicates promising new uses in medicine. Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due their ability to regulate cancer-related cell cycle pathways, leading to many beneficial effects such as tumor growth prevention, cell cycle obstruction, and cell death. The aim of this review is to summarize current knowledge on mechanisms of cannabinoids and their role in treating chemotherapy-induced nausea and vomiting, relieving cancer-associated pain, and obstructing tumor cell growth.

The Mouse Grimace Scale (MGS) was developed 10 years ago to assess pain through characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. A comprehensive scoping review of the academic literature was performed. The MGS has been employed mainly in evaluation of acute pain, particularly in the pain and neuroscience research fields. There has however been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method does allow detection of pain of a longer duration, up to a month post-initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.

Background: New regional techniques can improve pain management after nephrectomy. Methods: This study was a randomized controlled trial conducted at two teaching hospitals. Patients undergoing elective open and laparoscopic nephrectomy were eligible to participate in the trial. A total of 100 patients were divided into a quadratus lumborum block (QLB) group and a control (CON) group. At the end of surgery, but while still under general anesthesia, unilateral QLB with ropivacaine was performed on the side of nephrectomy for patients in the QLB group. The main measured outcome of this study was oxycodone consumption via a patient-controlled anesthesia (PCA) pump during the first 24 hours following surgery; other measured outcomes included postoperative pain intensity assessment, patient satisfaction with pain management, and persistent pain evaluation. Results: Patients undergoing QLB needed less oxycodone than those in the CON group (34.5 mg [interquartile range 23–40 mg] vs. 47.5 mg [35–50 mg]; p<0.001). No difference between the groups was seen in postoperative pain intensity measured on the visual analog scale, except for the evaluation at hour 2, which was in favor of the QLB group (p=0.03). Patients who received QLB were more satisfied with postoperative pain management than the CON group. Persistent postoperative pain was assessed with the Neuropathic Pain Symptom Inventory (NPSI) at months 1, 3, and 6 and was found to be significantly lower in the QLB group at each evaluation (p<0.001). We also analyzed the impact of the surgery type on persistent pain severity, which was significantly lower after laparoscopic procedures than open procedures at months 1, 3, and 6. Conclusions: QLB reduces oxycodone consumption in patients undergoing open and laparoscopic nephrectomy and decreases persistent pain severity months after hospital discharge.

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19 than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A2, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A2 from endothelial cells and macrophages stimulates platelets to release microvesicles which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases and lastly, examine the therapeutic targets and potential treatments for the two diseases.

The digital transformation of healthcare is advancing, leading to an increasing availability of clinical data for research. Perioperative big data initiatives were established to monitor treatment quality and benchmark outcomes. However, big data analyzes have long exceeded the status of pure quality surveillance instruments. Large retrospective studies nowadays often represent the first approach to new questions in clinical research and pave the way for more expensive and resource intensive prospective trials. As a consequence, utilization of big data in acute pain and regional anesthesia research considerably increased over the last decade. Multicentric clinical registries and administrative databases (e.g., healthcare claims databases) have collected millions of cases until today, on which basis several important research questions were approached. In acute pain research, big data was used to assess postoperative pain outcomes, opioid utilization, and the efficiency of multimodal pain management strategies. In regional anesthesia, adverse events and potential benefits of regional anesthesia on postoperative morbidity and mortality were evaluated. This article provides a narrative review on the growing importance of big data for research in acute postoperative pain and regional anesthesia.

Understanding neck pain is an important societal issue. Kinematic data from sensors may help to gain insight on the pathophysiological mechanisms associated with neck pain through a quantitative sensorimotor assessment of one patient. The objective of this study was to evaluate the potential usefulness of artificial intelligence with several Machine Learning (ML) algorithms in assessing neck sensorimotor performance. Angular velocity and acceleration measured by an inertial sensor placed on the forehead during the DidRen laser test in thirty-eight acute and subacute non-specific neck pain (ANSP) patients were compared to forty-two healthy control participants (HCP). Seven supervised ML algorithms were chosen for the predictions. The most informative kinematic features were computed using Sequential Feature Selection methods. The best performing algorithm is the Linear Support Vector Machine with an accuracy of 82% and Area Under Curve of 84%. The best discriminative kinematic feature between ANSP patients and HCP is the first quartile of head pitch angular velocity. This study has shown that supervised ML algorithms could be used to classify ANSP patients and identify discriminatory kinematic features potentially useful for the clinicians in the assessment and monitoring of the neck sensorimotor performance in ANSP patients.

Oral mucositis (OM) is inflammation of the mouth caused by damage to the mucous membranes that line the mouth and throat. It is a side effect of cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy, chemotherapy, and/or immunotherapy with immune checkpoint inhibitors. The etiology and pathogenic mechanisms of OM is complex and multifaceted, involving cytotoxicity (cell death), inflammation, infection, change in microbiome, and immune-mediated cytotoxicity. We summarize the literature about attempts to use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) to elucidate the biological pathways associated with the development or the severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and local environment (microbiomics).

Background: Transient receptor potential cation channel subfamily A member 1 (TRPA1) is expressed in trigeminal neurons and brain regions important in migraine pathogenesis and is activated by many migraine triggers. Epigenetic regulation of TRPA1 expression is important in pain transmission and neurogenic inflammation.Findings: TRPA1 channels change noxious stimuli into pain signals with the involvement of epigenetic regulation, including DNA methylation, histone modifications, and effects of micro RNAs (miRNAs) and long non-coding RNAs. TRPA1 may change epigenetic profile of many pain-related genes as it may modify enzymes establishing the epigenetic profile and expression of non-coding RNAs. TRPA1 may induce the release of calcitonin gene related peptide (CGRP), from trigeminal neurons and dural tissue. Therefore, epigenetic regulation of TRPA1 may play a role in efficacy and safety of anti-migraine therapies targeting TRP channels and CGRP. TRPA1 is also involved in neurogenic inflammation, important in migraine. The fundamental role of TRPA1 in inflammatory pain transmission may be epigenetically regulated. Conclusions: Epigenetic connections of TRPA1 may play a role in efficacy and safety of anti-migraine therapy targeting TRP channels or CGRP and they should be further explored for efficient and safe antimigraine treatment.

Pain is an unpleasant emotional and sensory experience. For many years orthodontists have been looking for an effective method of reducing this feeling of discomfort. In recent years, low-level laser therapy (LLLT) has taken hold in the orthodontic field. Among the countless advantages it can modulate the painful feeling. The aim of this research is to identify the use of photobiomodulation in subjects undergoing fixed orthodontic treatment, to reduce the pain and discomfort that it causes. The research was conducted from the Web of Science, Pubmed and Scopus databases. Only 14 of all articles met the inclusion and exclusion criteria and were therefore used to conduct the research. The different studies compared, in most cases, patients whose mouth was divided into a part treated with laser therapy and a placebo part. The results show a statistically significant difference in perceived pain between the irradiated arch and the non-irradiated arch. Three authors didn’t find statistically significant results in favour of low-laser therapy, but it is important to remember that they used different parameters. To obtain generally valid studies, with consistent and reproducible results, it is necessary to standardize the different parameters used that are independent by operator performing the procedure.

Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, 5‐aminoimidazole‐4‐carboxamide riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g. mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested in these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.

Aims: Multidisciplinary diabetic foot clinics have been shown to be an effective therapeutic model for reducing major amputations and mortality rates. The aim of this article is to assess the economic impact of the implementation of a multidisciplinary diabetic foot clinic in a hospital in Barcelona, Spain. Methods: Observational cost-benefit study of all subjects with diabetes admitted with the diagnosis of a major amputation due to diabetic foot from 2010 to 2020. Direct and indirect costs were compared before and after the introduction of the multidisciplinary diabetic foot clinic. Results: The individual cost per patient with diabetic foot was €14,768 before the implementation of the unit. After the implementation of the clinic, the expected cost was reduced to €5,985 due to a 40% reduction in the probability of hospitalization. Overall, the implementation of the clinic resulted in cost savings per patient valued at €8,783, of which, €7,165 are related to hospital benefits. Conclusion: The results of this analysis contributes to the evidence suggesting that multidisciplinary diabetic foot clinics are cost-effective, by demonstrating that they have a positive impact on patient health while also reducing the utilization of healthcare resources.

It is well known that low back pain (LBP) prevalence is high during the course of school age children’s lives. However, literature concerning the initial onset of back pain between ages of 3 and 11 years remains scarce. The present study aimed to analyze the prevalence of LBP in kindergarten and primary school students. 278 (9.9±2.1 years old; 52.2% girls) students from two public kindergarten and primary schools in Valencia, Spain participated in this cross-sectional study. The Nordic questionnaire on LBP was used to ask questions related to the duration of LBP symptoms over time. The lifetime prevalence of LBP was 47.5% (n = 132), a last year prevalence of 44.2% (n = 123), and a last week prevalence of 18.8% (n = 50) was reported. Boys and girls reached lifetime prevalence of 52.3% (n = 64) and 47.7% (n = 82) (χ2 = 1.978, p = .099), respectively. By age group, lifetime episodes of LBP also showed a higher prevalence with increasing age (χ2 = 32.637; p &lt; .001). In summary, our findings suggest that LBP increases with age. In addition, our results further strengthen the evidence that LBP onset could start as young as 10-years-old.

Low back pain (LBP) is a pandemic and costly musculoskeletal condition in the United States. Patients with LBP may endure surgery, injections, and expensive visits to emergency departments. Some suggest that using physical therapy or chiropractic in the earlier stage of LBP reduces the utilization of expensive health services and lowers the treatment costs. Nevertheless, there is no consistent evidence to declare which one of these methods is a cost-effective treatment within a short (less than a year) period of time. The purpose of this study was to investigate the cost-effectiveness of chiropractic versus physical therapy in the United States. A decision tree analytic model was used for estimating the economic outcomes. The findings showed that in the chiropractic group, the total average cost was $48.56 lower than the physical therapy group, and daily adjusted life years (DALY) was 0.0043 higher than the physical therapy group. Chiropractic care was shown to be a cost-effective alternative compared with physical therapy for adults with at least three weeks of low back pain over six months.

Spinal Cord Stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that Awake Anesthesia (AA), consisting in Target Controlled Intra-Veinous Anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with Minimal Invasive Surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or General Anesthesia (MISGA group), or by Laminectomy under General Anesthesia (LGA group). All in all, MISAA appears to show significantly better performance in terms of patient pain coverage, as well as improved secondary outcomes. One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

Acute low back pain (LBP) stands as a leading cause of activity limitation and work absenteeism, and its associated healthcare expenditures are expected to become substantial when acute LBP develops into a chronic and even refractory condition. Therefore, early intervention is crucial to prevent progression to chronic pain whose management is particularly challenging and for which the most effective pharmacological therapy is still controversial. Current guideline treatment recommendations vary and are mostly driven by expertise with opinion differing across different interventions. Thus, it is difficult to formulate evidence-based guidance when relatively few randomized clinical trials did explore the diagnosis and management of LBP while employing different selection criteria, statistical analyses, and outcome measurements. This narrative review aims to provide a critical appraisal of current acute LBP management by discussing the unmet needs and areas of improvement from bench-to-bedside and proposes multimodal analgesia as the way forward to attain an effective and prolonged pain relief and functional recovery in patients with acute LBP.

Motor control, movement impairment and postural control recovery targeted in rehabilitation could be affected by pain. The main objective of this comprehensive review is to provide a synthesis of the effect of experimental and chronic pain on postural control throughout the available literature. After presenting the neurophysiological pathways of pain, we demonstrated that pain, preferentially localized at low back or in the leg induced postural control alteration. While proprioceptive and cortical excitability seems modified with pain, spinal modulation assessment might provide new understanding of the pain phenomenon related to postural control. Literature highlight that the motor control of trunk muscles in patient presenting with low back pain could be dichotomized in two populations, where the first one over-activate trunk muscles, the second one under-activate trunk muscles, and both generating increase of tissues loading. Taking account all this findings, will help clinician to provide adapted treatment for managing both pain and postural control.

Ehlers–Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile EDS (hEDS) is the most frequent, and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hEDS is often associated with pain that not always allow the use of effective pain-reducing treatments. Patients with hEDS always talk about pain using a lot of descriptions. Eighty-nine patients with diagnosis of hEDS were recruited and evaluated. They were asked to write down what grief was to them. The texts were analyzed through LIWC. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and quality of metaphors was carried out. The results showed, depending on the level of pain perception, different language quality is evidenced. The greater the pain the lesser the positive effects and the greater the negative effects and dehumanizing metaphors. Moreover, greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for exploring illness experience and may help clinicians in the rehabilitation program.

Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Well-controlled chronic background pain during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). Results: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (Linear p-value = 0.1) and dyspnoea (Linear p-value =0.05). The ESAS and PSQI questionnaires confirmed these positive results (p<0.0001 and p=0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance

Interventional management of neuropathic pain (NP) is available to the many patients who do not attain satisfactory outcomes with pharmacotherapy, but evidence supporting this is sparse and fragmented. We attempted to summarize and critically appraise the existing data to identify strategies that yield maximum benefit, orient clinicians, and identify areas that merit further investigation. A two-round Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 26-item questionnaire prepared by the authors. Consensus on each statement was defined as either at least 80% endorsement or rejection after the second round. Thirty-five and 29 panelists participated in the first and second round, respectively. Consensus was reached in 20 out of 26 statements. There is sufficient basis to treat postherpetic neuralgias and complex regional pain syndromes with progressive levels of invasiveness and failed back surgery syndrome with neuromodulation. Radiculopathies and localized NP could be treated with peripheral blocks and neuromodulation, or pulsed radiofrequency. Non-ablative radiofrequency and non-paresthetic neuromodulation are efficacious and better tolerated than ablative and suprathreshold procedures. A graded approach, from least to most invasive interventions has the potential to improve outcomes in many patients with common refractory NP conditions. Preliminary promising data warrant further research on new indications, and technical advances might enhance the safety and efficacy of current and future therapies.

Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer’s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.

Background: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Objectives: To investigate the efficacy of manual therapy (MT) program combined with Capacitive and Resistive Electric Transfer (TECAR) therapy in individuals with CNSLBP. Method: Sixty adults with CNSLBP were randomly equally divided into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet and the third group (Control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 hours with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland-Morris Disability Questionnaire (RMDQ), Pressure Pain Threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both in the second week as well as in the one-month follow-up (p < .001). Between-groups differences were also noticed between the two intervention groups in the second week (p < .05). Differences in the RMDQ score in the second week and on the one-month follow-up were detected between the intervention groups and the control group (p < .001), while differences between the two intervention groups were only detected in the one-month follow-up (p < .001). Regarding the PPT values, differences were found mainly between the MT + TECAR and the control group and between the MT + TECAR and the MT group (p < .05), with the MT + TECAR group in most cases showing the greatest improvement compared to the other two groups, which remained statistically significant in the one-month follow-up (p < .05). Finally, both intervention groups improved the mobility of the lumbo-pelvic region in both time points compared to the control group without, however, statistically significant differences between them (p> .05). Conclusion: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in mobility of the lumbo-pelvic region by adding TECAR to the MT intervention.

Pain is frequently reported during cancer disease, and still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Thereby, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discuss the different options currently available to manage pain in (former) cancer patients in the light of progress made in the last decade. Major progress in the field are recent development of a chronic cancer pain taxonomy now included in International Classification of Diseases (ICD-11) and update of WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, opioids being considered as mainstay. The opioids crisis has prompted the reassessment of opioids use, both in cancer patients and cancer survivors. The review focuses on the current utilization of opioids, on the neuropathic pain component often neglected and on techniques and non-pharmacological strategies available which help to personalize patient’s treatment. Cancer pain management is now closer to the management of chronic non-cancer pain i.e. “an integrative pain care” aiming to improve patient’s quality of life.

Background: The thoracolumbar fascia (TLF) is thought to play a role in the development of LBP, but it is not yet clear which factor of TLF changes is a cause and which is an effect. Therefore, some studies used the cross-correlation function (CCR) to reveal time-dependent relationships between biomechanical and neuromotor factors. Methods: Ten patients with acute low back pain (aLBP) were matched to healthy controls. Simultaneous recording of surface electromyography (sEMG) of the erector spinae muscle (ES) and dynamic ultrasound (US) images of TLF deformation were performed during trunk extension. CCR functions and Granger causality were used to describe the relationship between the two measures. Results: CCR time lags were significant higher in the aLBP group (p = 0.04). Granger causality (GC) showed a direct effect of TLF deformation on ES activation only in the aLBP group (p &lt; 0.03). Conclusions: The results suggest that in aLBP, ES activity is significantly affected by TLF, whereas this relation-ship is completely random in healthy subjects studied with CCR and GC comparisons of dynamic US imaging and sEMG data signals. Fascia-related disturbances in neuromotor control, particularly due to altered muscle spindle functions, are suspected as a possible mechanism behind this.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Nociceptive threshold (NT) testing is widely used for the study of pain and its alleviation. The end point is a normal behavioural response which may be affected by restraint or unfamiliar surroundings leading to erroneous data. Remotely controlled thermal and mechanical NT testing systems were developed to allow free movement during testing and were evaluated in cats, dogs, sheep, horses and camels. Thermal threshold (TT) testing incorporated a heater and temperature sensor held against the animal’s shaved skin. Mechanical threshold (MT) testing incorporated a pneumatic actuator attached to a limb containing a 1 - 2mm radiused pin pushed against the skin. Both stimuli were driven from battery powered control units attached on the animal’s back, controlled remotely via infra-red radiation from a hand held component. Threshold reading was held automatically and displayed digitally on the unit. The system was failsafe with a safety cutout at a preset temperature or force as appropriate. The animals accepted the equipment and behaved normally in their home environment enabling recording of reproducible TT (38.5 – 49.8°C) and MT (2.7 – 10.1N); precise values depended on species, the individual and the stimulus characteristics. Remote controlled NT threshold testing appears to be a viable refinement for pain research.

The US opioid overdose epidemic has risen to an all-time high. Prescription opioids often serve as a gateway to illicit opioids which have appreciable overdose potential. Recent investigations have highlighted the efficacy and safety of marijuana-based products for pain management. Providing alternative pain treatment options may help mitigate the opioid epidemic. The distribution of codeine, fentanyl, hydrocodone, morphine, and oxycodone per 100K people and by 3-digit zip codes and overdose rates from 2014 to 2018 in California, which legalized recreational marijuana in 2016, were compared to Texas, where marijuana is functionally prohibited. Drug weights were obtained from the Automation of Reports and Consolidated Orders System and converted to oral morphine milligram equivalents. Overdose data was retrieved from the Centers for Disease Control’s WONDER database. California (-43.7%) and Texas (-27.3%) showed significant reductions in cumulative opioid distribution from 2014 to 2018. Opioid distribution per 100K people decreased -38.9% in California relative to -26.4% in Texas. Opioid and heroin overdoses increased between 1999 and 2019 by +11.6% in California but +272.7% in Texas. This evidence supports marijuana legalization as a mitigating factor to the opioid epidemic and opioid misuse.

: This article was not intended to be a complete report of a standard clinical trial. It is a report of the outcomes of preliminary data for validation of the CMECD procedure (Coletti Method of EMG ChemoDenervation) protocol for the treatment of chronic pain resulting from chronic muscle spasm. Methods are here detailed on how to approach the patient with chronic pain, identify the presence of chronic muscle spasm, undertake the treatment protocol and how to perform the follow up process to confirm that chronic pain secondary to chronic muscle spasm was the accurate diagnosis. Furthermore, this article presents the results of a cohort of more than 90 patients treated by the CMECD procedure regarding location and duration of prior pain, prior treatment strategies, degree of success in resolving pain and duration of relief. Outcome data consisting of patient and staff reporting of specific situations in which the chronic pain treatment was successful has been included to help establish the “believability” of outcome successes and to elucidate the potential life altering effects of successful treatment of chronic pain secondary to chronic muscle spasm. This article will hopefully increase the interest in this treatment protocol and increase the chance that a classical international clinical trial will be undertaken.