Abstract: Turmeric is a plant with multiple medicinal attributes. One of them being its analgesic effect. In this project the analgesic effect of the plant was evaluated with an inflammatory pain model: the 5% formalin model. Turmeric was administered to 250 g male Wistar rats (6 ± 2) provided by the Health Science department’s vivarium. The dose-response curve of the plant was per-formed observing the analgesic effect. Once the dose was selected, they were administrated within different turmeric protocols. 400 mg orally every 24 h for two weeks, another group with turmeric ad libitum for two weeks, the control group with 0.9% saline solution for two weeks, and a group with administration of metamizole prior to evaluation with 5% formalin. Subsequently, each rat was evaluated by 5% formalin intraplantarly and the number of rat paw twitches per 1 h was observed. The analysis of the data generated through the obtained results was carried out. The dose of 400 mg of oral turmeric was administered for two weeks without observing any collateral effects. An excellent analgesic effect was found in this protocol, as well as, in the ad libitum administration for two weeks compared to the control group. Likewise, turmeric presents a milder effect than metamizole, a well-known analgesic.

Ketamine as an old - new drug has variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine at standard doses is principally utilized for the induction and maintenance in surgical procedures. Beside its use in anesthesia and analgesia, recently studies had shown that ketamine find the place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Its mechanism of action is complex, but it mostly acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Ketamine is generally considered relatively secure and does not result in serious adverse effects when used at low doses and for short periods- Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drug.

Children with leukaemia experience difficulties adapting to medical procedures and to the chemotherapy’s adverse effects. Study’s objectives were to identify which coping strategies could be associated with the treatments’ factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. 125 patients (M = 6.79 years; SD = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the PPCI. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2=0.25) showed that, weighing the age factor (F=3.47; df=3; p=0.02), the number of episodes of fever (F=4.78; df=1; p=0.03), nausea (F=4.71; df=1; p=0.03) and mucositis (F=5.81; df=1; p=0.02) influenced the use of distraction. Cognitive self-instructions (R2=0.22) were influenced by the number of hospitalizations (F=5.14; df=1; p=0.03) and mucositis (F=8.48; df=3; p=0.004) and by child’s age (F=3.76; df=3; p=0.01). Children who sought parental support more frequently (F=9.7; df=2; p=0.0001) and who tended not to succumb to a catastrophic attitude (F=13.33; df=2; p=0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social support.

The present clinical study was approved by the Review Board for Animals Care of the University of Parma prot N. 03/CESA /2023, which provided a consent to the clinical study: regulation (EU) no. 536/2014. (22A01712) (GU General Series n.65 of 18-03-2022); European Law (O.J. of E.C. L 358/1 12/18/1986), and USA Laws (Animal Welfare Assurance No A5594-01, Department of Health and Human Services, USA). The owners signed a voluntary informed consent form prior to the dogs’ enrollment in the study. Twenty female dogs, aged 1±1.5 months, and weighing 16± 0.5 kg were enrolled in the study. The inclusion criterion of the patients was to undergo ovariectomy surgery; dogs enrolled in this study had normal physiological, haematological and biochemical parameters.

Purpose: The study aimed to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) in reducing blood loss in patients undergoing total knee replacement. Materials: A retrospective study on 530 individuals with a mean age of 71,44 years after posterior stabilized total knee arthroplasty was evaluated. Patients were divided into three groups, corresponding to the method of bleeding control: I - patients without additional bleeding protocol (control group); II - patients with iV TXA administration (TXA group); III - patients with exact TXA protocol combined with intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured as a substitute for blood loss by maximal Hb drop compared to preoperative Hb level. Results: The mean hospitalization for patients from the control group was 7.02 (SD 1.34) days, 6.08 (SD 1.06) days for the TXA group, and 5.56 (SD 0.79) for the TXA + LIA group. The most significant hemoglobin drop was found in the control group, which amounted to an average of 30.08% output value. In the TXA group, the decrease in hemoglobin was, on average, 25.17% (p<0.001), and in the TXA + LIA group, it was 23.67% (p<0.001). A decrease in the rate of allogeneic blood transfusions was observed, which was 24.4% in the control group, 9.9% in the TXA group, and 8% in TXA + LIA group (p<0.01). Conclusions: Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia statistically significantly reduces blood loss in patients after total knee replacement.

Use of local anesthesia at the time of ring castration and tail docking can improve lamb welfare. However, few local anesthetics are registered for sheep, and data on their duration of effect is limited. Three studies were conducted to evaluate the efficacy of procaine (P), lidocaine (L) and bupivacaine (B) in terms of observed alleviation of behavioral responses to castration and/or tail docking in 10-min blocks in the first 60 min post treatment. In each study, comparisons were made between two groups of lambs castrated and/or tail docked with rubber rings and either receiving the agent using the NUMNUTS® instrument (N) or receiving no anesthetic agent (RR). Acute pain behavior was lower in NL (n = 28) than RRL (n = 15) males in the first 10 min post procedure (P &lt; 0.05); lower in NB (n = 16) than RRB (n = 16) males in periods 10-20 min (0.05 &lt; P &lt; 0.01), 20-30 min (P &lt; 0.05) and 40-50 min (0.05 &lt; P &lt; 0.01); lower in NB (n = 16) than RRB (n = 16) females between 20 and 40 min post-procedure (0.05 &lt; P &lt; 0.01); lower in NP (n = 8) than RRP (n = 7) males in period 10-20 min (0.05 &lt; P &lt; 0.01), and lower in NP (n = 9) than RRP (n = 9) females in periods 0-10 min (0.05 &lt; P &lt; 0.01), and 10-40 min (P &lt; 0.05). Analgesic benefits were modest, and the effects of procaine appear to last longer than lidocaine, while bupivacaine is slower to take effect than either procaine or lidocaine but may provide longer lasting analgesia. The duration of action of local anesthetics is short in sheep, and detailed behavioral evaluations are required in the first hour post procedure to establish efficacy.

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year, and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. Levobupivacaine PCA group had the best preserved HGS after 1 year (P=0.022). The most significant predictor of the 5-year outcome was HGS (P=0.03). Although the best survival after 5 and 10 years was registered in the bolus levobupivacaine group, statistical significance was not reached (P=0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival. A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study. Trial number NCT05829707

Docking the tail of lambs is a standard husbandry procedure and is achieved through several techniques including clamps, hot or cold knives and latex rings, the last of which is the most popular. All tail docking methods cause acute pain which can be reduced by application of local anesthetic, however precise anatomical injection for optimal efficacy requires considerable skill. This pen trial evaluated the ability of local anesthetic delivered with a dual function ring applicator / injector to alleviate acute tail docking pain. Thirty ewe lambs were assigned to one of three treatment groups (n = 10 per group): ring plus local anesthetic (Ring LA), ring only (Ring) and sham handled control (Sham). Lambs were videoed and behavior categorized every 5 minutes for the first hour and every 10 min for the subsequent 2 hours after treatment. There was a significant effect (p &lt; 0.001) of treatment on total active pain related behaviors in the first hour, with Ring lambs showing higher counts compared to Ring LA or Sham. Ring lambs also displayed a significantly higher count of combined abnormal postures (p &lt; 0.001) than Ring LA or Sham lambs. Delivery of 1.5ml of 2% lignocaine via the dual action device abolished abnormal behaviors and signs of pain in Ring LA lambs. However, lambs in the Ring LA group spent less time attempting to suckle compared to Ring and Sham lambs, suggesting that some residual discomfort remained.

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.

Analgesic products for piglet castration are critically needed. This requires extensive animal experimentation such as to meet regulatory-required proof of efficacy. At present, there are no validated methods of assessing pain in neonatal piglets. This poses challenges for investigators to optimize trial design and to meet ethical obligations to minimize the number of animals needed. Pain in neonatal piglets may be subtle, transient and / or variably expressed and, in the absence of validated methods, investigators must rely on using a range of biochemical, physiological and behavioural variables, many of which appear to have very low (or unknown) sensitivity or specificity for documenting pain, or pain-relieving effects. A previous systematic review of this subject was hampered by the high degree of variability in the literature base both in terms of methods used to assess pain and pain mitigation, as well as in outcomes reported. In this setting we provide a narrative review, to assist in determining the optimal methods currently available to detect piglet pain during castration and methods to mitigate castration-induced pain. In overview, the optimal outcome variables identified are nociceptive motor and vocal response scores during castration, and quantitative sensory-threshold response testing and pain-associated behaviour scores following castration.

Background and objectives: Traditional intravenous, patient-controlled analgesia (PCA) uses a fixed-rate continuous background infusion mode. However, some patients suffer from inadequate analgesia or opioid-related adverse effects due to the biphasic pattern of postoperative pain. Therefore, we investigated the postoperative analgesic efficacy of PCA using an optimizing background infusion mode (OBIM), where the background injection rate varies depending on the patient's bolus demand. Materials and Methods: We prospectively enrolled 204 patients who underwent laparoscopic cholecystectomy in a randomized, controlled, double-blind study. Patients were allocated into either the optimizing (group OBIM) or the traditional background infusion group (group TBIM). The numeric rating scale (NRS) score for pain was evaluated at admission to and discharge from the recovery room, as well as at the 6th, 24th, and 48th postoperative hours. Data of bolus demand count, total infused volume, and background infusion rate was downloaded from the PCA device at 30-min intervals until the 48th postoperative hour. Results: The NRS score was not significantly different between groups throughout the postoperative period (P = 0.621), decreasing with time in both groups (P < 0.001). The bolus demand count was not significantly different between groups throughout (P = 0.756). The mean cumulative infused PCA volume was lower in group OBIM [84.0 (95% confidence interval: 78.9−89.1) mL) than in group TBIM [102 (97.8−106.0) mL] (P < 0.001). The background infusion rate was significantly different between groups throughout (P < 0.001); it was higher in group OBIM than in group TBIM before the 12th postoperative hour, and lower from the 18th to the 48th postoperative hours. Conclusions: The OBIM combined with bolus dosing is useful in that it reduces the cumulative PCA volume compared to the TBIM combined with bolus dosing, while yielding comparable postoperative analgesia and bolus demand in patients undergoing laparoscopic cholecystectomy.

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided bra-chial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 ml kg-1), and eight received lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 minute-1). Rescue analgesia was provided with Fentanyl IV. Carprofen was administered at the end of surgery. Post-operative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered accord-ing to pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to no rabbits in BPB. How-ever, rabbits in both groups had similar pain scores and there was no difference in administration of postoperative analgesia. There were no significant differences in food intake or faeces produc-tion over 18 hours, and no significant differences in distance travelled, or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively both groups were comparable.

The administration of regional neuraxial analgesia for pain relief during labor is widely recognized as a safe and effective method involving medication delivery into the epidural or subarachnoid space in the lower back. This study proposes an innovative semantic image segmentation methodology emphasizing enhanced interpretability using convolutional Random Fourier Features and layer-wise weighted class-activation maps tailored explicitly for foot segmentation in regional analgesia monitoring. Namely, our contribution is twofold: i) a novel Random Fourier Features layer is introduced to deal with image data to enhance three well-known architectures (FCN, UNet, and ResUNet); ii) three novel quantitive measures are presented to evaluate the interpretability of a given deep learning model devoted to segmentation tasks. Our approach is rigorously evaluated on a demanding dataset of foot thermal images from pregnant women who received epidural anesthesia. Its small size and considerable variability characterize the dataset. Our validation results demonstrate that the proposed methodology not only achieves competitive foot segmentation performance but also significantly enhances the explainability of the process, rendering it well-suited for applications such as epidural insertion during labor.

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.

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.

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.

Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on antinociceptive activity and itch-associated scratching behavior (LLS) in mice, and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose, and inhibited IL-31-induced LLS. These results suggested that repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. IL-31 and morphine combination increased analgesic action which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.

The theory that an itch inhibits pain has been refuted; however, previous research did not investigate this theory for interleukin-31 (IL-31)-induced itch. Previously, we have found that morphine-induced antinociception was partially reduced in IL-31 receptor A (IL-31RA)-deficient (IL-31RAKI) mice, indicating that IL-31RA may play an important role in morphine-induced peripheral antinociception. In the present study, we evaluated the effect of IL-31-induced analgesia on a 2,4,6-trinitrochlorobenzene (TNCB)-sensitized mice using a hot-plate test. This test evaluated the antinociceptive activity of morphine, and non-steroidal anti-inflammatory drugs (NSAIDs). Repeated pretreatment with IL-31 showed significant antinociceptive action. Furthermore, its combination with morphine, but not with NSAIDs, increased the analgesic action. In contrast, treatment with TNCB and capsaicin decreased antinociception. Moreover, TNCB increased IL-31RA expression in the dorsal root ganglia at 24 h, whereas capsaicin inhibited it. The comparative action of several analgesics on TNCB or capsaicin was evaluated using a hot-plate test, which revealed that the antinociceptive activity was decreased or disappeared in response to capsaicin-induced pain and in IL-31RAKI mice. These results indicate that the analgesic action of IL-31 involves the peripheral nervous system, which affects sensory nerve. These results provide a basis for developing novel analgesics using this mechanism.

Regional anesthesia in postoperative pain management have developed in recent years, especially with the advent of fascial plane blocks. This study aims to compare the ultrasound-guided bilateral erector spinae plane block (ESPB) versus bilateral transversus abdominis plane block (TAPB) on postoperative analgesia after laparoscopic or robotic urologic surgery. This was a retrospective observational study; 97 patients (ESPB-group) received bilateral ultrasound-guided ESPB with 20 mL of ropivacaine 0.375% plus 0.5 mcg/kg of dexmedetomidine in each side at the level of T7-T9, and 93 patients (TAPB-group) received bilateral ultrasound-guided TAPB with ropivacaine 0.375% or 0.25%. The primary outcome was post-operative numeric rating scale (NRS) pain score, which was significantly lower in the ESPB-group on postoperative days 0, 2, and 3 (p=0.012, p=0.016 and p=0.004). Concerning the secondary outcomes, consumption of ropivacaine was significantly lower in ESPB-group (p<0.001) and the total amount of analgesic rescue doses was significantly lower in the ESPB-group than TAPB-group in postoperative days from 2 to 4 (1 vs 3, p>0.001). Incidence of postoperative nausea and vomiting was higher in the TAPB-group and no block related complications were observed. We conclude that ESPB provide better postoperative pain control with less consumption of local anesthetic and less total rescue analgesic therapies.