Abstract: Background Epidural analgesia (EA) is widely used in pancreatic surgery but is associated with hypotension and delayed recovery. The shift towards minimally invasive surgery has led to exploration of alternative multimodal analgesia strategies. Methadone, with its unique pharmacological properties, may further optimize recovery. Methods This retrospective cohort study included 213 patients undergoing pancreatic resection, receiving EA (n=63), multimodal analgesia without methadone (MA; n=92), or with methadone (MM; n=58). MA and MM included intravenous ketamine, lidocaine and continuous wound infiltration. Primary outcome was maximum daily postoperative pain scores. Secondary outcomes included opioid consumption, vasopressor use, mo-bilization, bowel recovery, urinary catheter duration, and ICU/hospital stay. Results Compared with EA, pain scores were slightly higher in MM (mean difference 2.22; 95% CI 1.22–3.90; p=0.01), and in MA (mean difference 2.06; 95% CI 0.99–4.30; p=0.06). Opi-oid use was comparable between MM and EA (OR 0.99, 95% CI [0.98, 1.00], p=0.20), and significantly lower in MA (OR 0.97, 95% CI [0.96, 0.98], p< 0.001). Both MA and MM demonstrated reduced vasopressor requirements (both 0 vs 2.0 median days) and shorter urinary catheterization durations (MA 1.2 MM 1.9 vs EA 4.0 median days). MA improved mobilization (0 vs 1 median days; OR 0.52, p=0.03) and bowel recovery (OR 0.76, p=0.02). ICU stay was longer in EA due to routine ICU admission for open surgery. Conclusions Multimodal analgesia with or without methadone, offer alternative strategies in pan-creatic surgery. While EA provides superior pain control, multimodal regimens are associated with improved functional recovery.

Abstract: A 15-year-old female developed refractory Complex Regional Pain Syndrome (CRPS) Type I of the left hand following metacarpal fixation. Conservative therapy and hand rehabilitation failed, resulting in persistent allodynia and functional loss. She was admitted for multimodal analgesia combining subanesthetic ketamine infusion, gabapentin, and a tunneled supraclavicular continuous nerve catheter delivering ropivacaine. Pain decreased from 7/10 at rest to 0/10 within 48 hours. Allodynia has resolved, and motor function has fully recovered. The catheter was removed nine days later without complication, and pain remission persisted. This case demonstrates a safe and effective multimodal strategy for adolescent CRPS integrating central and peripheral desensitization mechanisms.

Abstract: Background: Pain associated with vascular disorders has traditionally been regarded as predominantly nociceptive, resulting from ischemia, inflammation, and tissue injury. However, emerging evidence indicates that neuropathic and nociplastic processes frequently coexist, giving rise to a complex, mixed-pain phenotype. This multidimensional nature of vascular pain reflects overlapping mechanisms of peripheral nerve injury, neuroinflammation, and central sensitization, which may explain the limited efficacy of purely nociceptive-oriented therapies. Objective: This protocol describes the methods for a systematic review and meta-analysis aimed to determine the pooled prevalence of nociceptive and neuropathic pain features in patients with vascular pain, to synthesize current evidence supporting nociplastic mechanisms, and to evaluate treatment outcomes according to mechanistic categories of intervention. Methods: This protocol outlines a comprehensive search strategy to identify observational and interventional studies involving adult patients with arterial, venous, or mixed vascular pain. Meta-analyses will estimate pooled prevalence rates of neuropathic pain features and aggregate effect sizes for pain reduction and responder rates, stratified by causal vascular, pharmacological, and neuromodulatory treatments. Risk of bias will be assessed using validated tools, and the certainty of evidence will be graded according to GRADE recommendations. Detailed eligibility criteria, data extraction procedures, and statistical analysis plans are specified. Discussion: The findings from this planned systematic review and meta-analysis will enhance understanding the mechanistic composition of vascular pain, promoting mechanism-based analgesic approaches, guiding personalized treatment strategies, and informing future health-economic evaluations. The protocol is registered in PROSPERO (CRD420251132877).

Abstract: Anesthetic protocols for non-invasive immobilization of Black Vultures (Coragyps atratus) and Turkey Vultures (Cathartes aura) for procedures lasting up to two hours are lacking. This study directly evaluated the safety and efficacy of a multimodal anesthetic protocol in 11 Black Vultures and 4 Turkey Vultures undergoing electroretinography (ERG). Vultures were anesthetized with intramuscular dexmedetomidine (5 μg/kg), midazolam (0.2 mg/kg), butorphanol (0.2 mg/kg), and ketamine (5 mg/kg) (DMBK), followed by isoflurane induction and maintenance. All vultures were mechanically ventilated to maintain consistent end-tidal CO₂. Monitored parameters included sedation and recovery quality, heart and respiratory rates, hemoglobin oxygen saturation, non-invasive blood pressure, body temperature, and end-tidal concentrations of CO₂, isoflurane, and oxygen. All vultures achieved profound sedation with smooth induction and a median isoflurane maintenance concentration of 1.4% for approximately two hours. Recovery was rapid and uneventful. Heart rates ranged from 60 to 119 beats/min. Mean arterial blood pressure averaged 149 mmHg in Black Vultures and 158 mmHg in Turkey Vultures, with Turkey Vultures showing significantly higher diastolic pressure. A second-degree heart block was detected in one Black Vulture but required no treatment. All ERG procedures were completed successfully. The DMBK protocol provided profound sedation in both species, maintained a stable cardiorespiratory state throughout isoflurane maintenance, and enabled uneventful rapid recovery. These findings support DMBK with the cardiorespiratory monitoring system as a safe and effective regimen for anesthetizing vultures and likely other similarly sized raptors requiring non-invasive immobilization.

Abstract: Background: Interventional neuroradiology (INR) is a minimally invasive procedure that is often performed under general anesthesia. A potential complication, emergence agitation (EA), can hinder immediate and accurate postoperative neurological assessments. Sevoflurane and propofol are common anesthetics used for these procedures. This study aimed at comparing the incidences of EA arising from sevoflurane-based anesthesia versus propofol-based total intravenous anesthesia (TIVA).Methods: Eighty patients scheduled for INR under general anesthesia were randomly allocated into two groups. The sevoflurane group (n=40) received induction with propofol, fentanyl, and cisatracurium, followed by sevoflurane for maintenance. The propofol group (n=40) received a target-controlled infusion (TCI) of propofol for both induction and maintenance. Anesthetic depth was maintained at a Bispectral Index (BIS) of 40-60 in both groups. The primary outcome was the incidence of EA, which was assessed using the Richmond Agitation-Sedation Scale (RASS). Secondary outcomes consisted of time to recovery, pain scores, postoperative nausea and vomiting, and hemodynamic instability.Results: No incidences of emergence agitation (RASS > 0) were observed in either group. However, the sevoflurane group required a significantly higher dose of ephedrine to manage intraoperative hypotension compared to the propofol group (p=0.031).Conclusion: In patients, who had undergone interventional neuroradiology, there was no difference in the incidence of emergence agitation between sevoflurane and propofol-based anesthesia. However, propofol-based TIVA may be associated with better intraoperative hemodynamic stability, as evidenced by a lower vasopressor requirement.

Abstract:

Background/Objectives: This pragmatic randomized controlled trial aimed to evaluate the efficacy of ultrasound-guided supraclavicular nerve (SCLN) block compared to standard pain management in patients with acute displaced clavicle fractures (CF) in an emergency department (ED) setting. Secondary outcomes included the time to first request for analgesics, opioid consumption, and patient satisfaction. Methods: Forty-one patients with acute displaced CF were randomized to receive either a SCLN block (n=19) or routine pain management (n=22). The primary outcome pain intensity was recorded upon admission and at 1, 2, 4, 6, 12, and 24 hours thereafter. The co-primary outcome patient satisfaction was evaluated after 24 hours. Pain medication, adverse reactions and adverse events, were documented for 24 hours. Results: Pain intensity, as measured by the Numeric Rating Scale (NRS), was significantly lower in the SCLN group at all time points within the first 12 hours (p<0.01). After one hour, 68% of patients in the SCLN group reported an NRS of 0-2, compared to 19% in the control group. The time to first request for pain medication was distinctly longer in the SCLN group (9.1 hours vs. 0.7 hours). In two out of 19 patients, the SCLN could not be clearly identified due to challenging ultrasound conditions, necessitating a cervical plexus block. Four patients in the block group reported adverse reactions. Satisfaction with pain management in the ED was significantly higher in the SCLN group (p=0.001), with 85% of patients indicating they would choose the block again in the event of a recurrence. Conclusions: The selective SCLN block provides a highly effective analgesia compared to standard pain management in patients with acute CF, with the most pronounced effect observed within the first 12 hours. Patient acceptance of the procedure was high.

Abstract: Postoperative pain following pediatric tonsillectomy remains a significant clinical challenge. Inadequate management leads to delayed recovery, dehydration, and in-creased healthcare utilization. Multimodal analgesia, including combining systemic analgesics, local anesthetic techniques, and adjunctive medications, has emerged as the standard of care. This review highlights current perioperative pain management strategies, evaluates the role of methadone as an alternative opioid, and explores future directions in optimizing analgesia for pediatric patients undergoing tonsillectomy procedures. Local infiltration and nerve blocks provide site-specific pain relief, reducing opioid requirements and improving patient comfort. A comprehensive understanding and careful selection of analgesic regimens are crucial for enhancing outcomes in this population.

Abstract: Background: The practice of discontinuing mechanical ventilation during cardiopulmonary bypass (CPB) has been widely adopted in various cardiac surgery centers. Nonetheless, concerns have emerged regarding its possible adverse effects on postoperative pulmonary function. This study aimed to evaluate the effects of discontinued mechanical ventilation during CPB on postoperative gas exchange, X-ray results, ICU stay, mortality, reintubation, re-exploration, and bleeding. Methods: A prospective observational study was performed involving adult patients scheduled for elective cardiac surgery requiring CPB. Participants were divided into two groups according to their intraoperative ventilation strategy: one group had ventilation halted for a period required to perform surgical intervention (non-ventilated group), while the other maintained it (ventilated group) throughout CPB. Postoperative arterial carbon dioxide levels (PaCO2), arterial partial pressure of oxygen (PaO2), PaO2/FiO2 ratio (P/F ratio), arterial oxygen saturation (SaO2), and the ratio of PaCO2 to minute ventilation (PaCO2/MV) were measured at induction, postoperatively (in the ICU), and in a 24 h postoperative period. Chest X-ray data, mechanical ventilation time, LOS in ICU, re-exploration, reintubation, and bleeding parameters were documented. Analyses were also conducted across seven distinct age categories: <30, 30–40, 40–50, 50–60, 60–70, 70–80, and >80 years. Results: Individuals in the non-ventilated group exhibited elevated postoperative PaCO2 and PaCO2/MV ratios and lower postoperative P/F ratios. The difference in gas exchange leveled off within 24 h. There was no difference in the incidence of atelectasis (postoperatively in a 24 h period), in mechanical ventilation time, LOS in ICU, or mortality. Interestingly, postoperative PaCO2/MV peaked in the 40–50-year age group. Conclusions: Continued mechanical ventilation during CPB correlates with better postoperative gas exchange and better CO2 clearance. These results imply that maintaining low tidal volume ventilation during CPB may provide benefits, especially for patients aged 40–60 years.

Abstract: Pain medicine is undergoing a paradigm shift, shaped not only by advances in biomedical research but also by the rapid integration of engineering innovations into clinical practice. The subjective nature of pain, long regarded as an obstacle to accurate diagnosis and effective treatment, is increasingly being addressed through objective, technology-driven approaches. Clinical engineering, a multidisciplinary field that merges biomedical engineering, informatics, and clinical sciences, has become a pivotal force in this transformation. Recent years have witnessed the emergence of sophisticated wearable sensors, capable of continuously tracking biomechanical, electrophysiological, and autonomic signals to capture the dynamic profile of pain in real-world contexts. In parallel, breakthroughs in neuroimaging and neurophysiological monitoring are unveiling objective biomarkers of nociceptive and neuropathic processes, providing unprecedented insights into the pathophysiology of pain chronification. On the therapeutic front, innovations in neuromodulation, including adaptive spinal cord stimulation, dorsal root ganglion stimulation, and non-invasive brain stimulation, have been empowered by closed-loop engineering designs and miniaturized devices that enhance precision and patient comfort. Rehabilitation robotics and nanotechnology-based drug delivery systems further expand the therapeutic armamentarium, integrating personalized feedback and targeted interventions. Beyond devices, artificial intelligence and machine learning now occupy a central role in predictive modeling and decision support, enabling clinicians to tailor interventions, anticipate treatment responses, and stratify risk with greater accuracy. This convergence of engineering and medicine is reshaping pain care into a more mechanistic, personalized, and proactive discipline. This review synthesizes these advances, while critically examining ethical, regulatory, and translational challenges that must be addressed to ensure equitable and sustainable implementation.

Abstract: Cardiac pain is difficult to diagnose and treat in part because existing models fail to capture human neuro-cardiac signaling. This review examines how iPSC-derived cardiomyocytes and sensory neurons in co-culture and organoid systems model ischemic and neuro-immune mechanisms, and how such platforms enable regenerative and neuromodulatory translation. We identify key barriers (maturation, heterogeneity, scalability, safety) and propose priorities to bridge discovery and clinical application.

Abstract: Cardiopulmonary interactions represent a complex physiological interplay that becomes critically relevant in patients undergoing mechanical ventilation, particularly with non-invasive modalities. This narrative review explores the pathophysiological basis and clinical implications of heart–lung interactions during non-invasive ventilation (NIV), with a focus on how positive pressure influences biventricular function. We examine how changes in intrathoracic pressure affect right and left ventricular preload and afterload, and how these effects are modulated by ventilation settings, underlying disease states, and ventricular interdependence. Special emphasis is placed on the role of echocardiography as a dynamic tool for assessing hemodynamic status at the bedside. Parameters such as TAPSE, S’ wave, MAPSE, LVOT-VTI, and vena cava indices are discussed in the context of fluid responsiveness, cardiac function, and weaning-induced pulmonary edema (WIPO). The review also addresses the dual role of PEEP—therapeutic when promoting alveolar recruitment, but potentially harmful when leading to RV overload through increased pulmonary vascular resistance. In critically ill patients, understanding and managing heart–lung interactions can be the key to preventing hemodynamic instability. Integrating ultrasound monitoring with tailored ventilatory strategies allows clinicians to better titrate support, minimize cardiovascular compromise, and improve outcomes. This review aims to provide a comprehensive framework for clinicians to interpret and manage heart–lung interactions effectively in the setting of non-invasive respiratory support.

Abstract: Acute Respiratory Distress Syndrome (ARDS) is a severe condition that often necessitates prolonged mechanical ventilation, which carries a high risk of complications and increased mortality. This case report describes the successful application of an early percutaneous dilatational tracheostomy (PDT) in a 61-year-old male with severe ARDS due to community-acquired pneumonia (CAP)-induced sepsis and type I respiratory failure. This case suggests that early PDT is a safe and effective way to reduce the risks of prolonged mechanical ventilation in severe ARDS patients, leading to a better recovery and shorter ICU stay.

Abstract:

Background/Objectives: Abdominal aortic aneurysms (AAAs) are exceedingly rare in pediatric patients but carry a significant risk of rupture, necessitating urgent surgical repair. Postoperative pain management following open AAA repair is particularly challenging and ultrasound-guided rectus sheath blocks (RSBs) offer a targeted and lower-risk alternative for midline abdominal incisions. Methods: We present an 8-yeaer old male who underwent open infrarenal AAA repair. Multilevel bilateral ultrasound-guided RSBs were performed at T7, the umbilicus and T12 using a mixture of liposomal bupivacaine, bupivacaine, and dexamethasone. Results: Postoperative pain scores remained consistently low through postoperative day (POD) 6, with minimal opioid requirements. Functional recovery was rapid, with sitting achieved by POD 1 and ambulation by POD 2. Plasma bupivacaine concentrations remained within safe limits throughout hospitalization. Conclusions: Multilevel bilateral RSBs with liposomal bupivacaine and dexamethasone provided prolonged opioid-sparing analgesia, facilitated early mobilization, and supported enhanced recovery in this complex pediatric surgical case.

Abstract: Chronic pain remains a major clinical challenge, with current treatments often providing insufficient relief. Oxytocin, classically recognized for its roles in reproduction and social bonding, has gained increasing attention for its potential involvement in pain modulation. Evidence suggests that oxytocin influences both nociceptive processing and broader dimensions of pain, including stress regulation, emotional appraisal, and coping. Despite this promise, clinical findings remain mixed. In this opinion paper, we summarize and discuss the rationale and current clinical evidence for the role of oxytocin in chronic pain (management), highlighting key research gaps and outlining future directions focused on: endogenous oxytocin system variability, biological modulators of its effects, dosing and timing strategies, and the role of psychosocial context. We propose that oxytocin should be reconceptualized not as a straightforward analgesic, but as a biopsychosocial adjuvant that strengthens resilience and coping. Positioning oxytocin within this framework may clarify for whom, when, and under what conditions oxytocin can be most effective, and ultimately guide its translational potential in chronic pain management.

Abstract: Chronic pain represents a complex debilitating condition that extends beyond the protective function of physiological pain, often persisting as an independent disease entity. Chronic primary and secondary pain syndromes reflect a multifaceted continuum involving nociceptive, neuropathic and nociplastic mechanisms. The maladaptive plasticity of the peripheral and central nervous system (encompassing the ascending and descending pain pathways) sustains hypersensitivity and correlates with comorbid alterations in mood, cognition, sleep, and fatigue, underpinned by functional reorganization of brain networks. In this scenario traditional analgesics frequently demonstrate limited efficacy, while current guidelines recommend antiepileptic agents and antidepressants, particularly gabapentinoids and duloxetine, a first line pharmacological options. This review explores the mechanistic rationale and clinical evidence supporting the combined use of gabapentinoids and duloxetine in chronic pain management. These agents act on distinct yet complementary targets: gabapentinoids reduce excitatory neurotransmission via modulation of calcium channel activity, while duloxetine restores descending noradrenergic inhibition and alleviates comorbid symptoms. Clinical trial and meta-analyses highlight their individual efficacy in diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. Among gabapentinoids, pregabalin exhibits a favorable pharmacokinetic profile that allows rapid titration and demonstrates effectiveness against anxiety-related sleep disorders. Importantly, emerging evidence suggests that their combination may yield superior pain relief and functional improvement compared with monotherapy, particularly in patients with residual pain. This review provides a proof of concept by bridging theoretical knowledge and real-life clinical settings aiming to develop treatment protocols based on predominant pain mechanisms that can effectively control hypersensitivity and improve quality of life.

Abstract: Objective: This study aimed to compare the efficacy and safety of ultrasound-guided quadratus lumborum block (QLB) versus transversus abdominis plane block (TAPB) in laparoscopic colorectal cancer surgery within an Enhanced Recovery After Surgery (ERAS) protocol. Methods: A two-center, prospective, randomized controlled trial was conducted with 182 patients (80 QLB, 102 TAPB), of whom 114 were matched via propensity score analysis (57 per group). Both groups received standardized anesthesia and postoperative analgesia. Primary outcomes included intraoperative remifentanil consumption and postoperative pain scores (VAS). Secondary outcomes encompassed hemodynamic stability, time to first flatus, ambulation, hospital stay, and adverse events. Results: QLB significantly reduced intraoperative remifentanil use (P = 0.0138) and provided superior early postoperative analgesia (lower VAS scores at 15 min, 6 h, and 12 h; P < 0.05). Despite delayed first flatus (58.49 ± 53.06 vs. 34.34 ± 19.74 hours, P = 0.002), QLB shortened hospital stays (median 5.60 vs. 8. 00 days, P = 0.029). Hemodynamics and adverse events were comparable between groups. Conclusion: QLB outperformed TAPB in opioid-sparing, early pain relief, and recovery acceleration, aligning with ERAS goals. Its broader nerve blockade may delay gastrointestinal recovery but ultimately enhances overall outcomes. Multicenter validation and long-term follow-up are warranted.

Abstract: Objective:This study aimed to assess the clinical outcomes of three lung isolation techniques inthoracic surgery: video-assisted double-lumen tube (VDLT), bronchial blocker (BO), and their combined use. The primary outcomes were peak airway pressure, lung ventilation time, hemodynamic parameters, and postoperative recovery, providing evidence to guide the optimal selection of lung isolation methods for clinical practice.Methods:A prospective randomized controlled trial was conducted from May 2020 to May 2024, involving 135 patients scheduled for thoracic surgery. Patients were randomly assigned into three groups: VDLT group (n=45), BO group (n=45), and VDLT+BO combined group (n=45). Key parameters, including peak airway pressure, positioning time, ventilation time, hemodynamic data, and postoperative recovery outcomes, were closely monitored. Statistical analyses, including t-tests, ANOVA, and multivariate regression, were used to assess the impact of each lung isolation method on arterial oxygen partial pressure (PaO₂) and postoperative pneumonia risk.Results:The combined VDLT+BO approach demonstrated significant advantages over the single-device techniques. It lowered peak airway pressure (22.61±1.49 mmHg vs. 27.11±1.66 mmHg, P<0.001), reduced positioning time (3.98±1.03 minutes vs. 7.18±1.27 minutes, P<0.001), and improved PaO₂ (4.70 mmHg, P<0.001). Furthermore, the VDLT+BO group exhibited a significantly lower incidence of postoperative pneumonia (8.9% vs. 24.4%, P=0.050). This approach also reduced postoperative pain scores (3.73±0.93), shortened hospital stay (4.24±1.07 days), and decreased hospitalization costs by 27.4%. Multivariate analysis identified positioning time and BMI as key factors influencing the incidence of postoperative pneumonia.Conclusion:The VDLT+BO combined approach effectively enhances lung isolation during thoracic surgery by reducing airway injury risk, improving oxygenation, and accelerating postoperative recovery, while also lowering medical costs. This combination offers a more efficient alternative to traditional methods and should be considered for broader clinical application. Future studies should examine its adaptability in different surgical contexts and explore its long-term clinical effects.

Abstract: Background/Objectives: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the HMGCL gene. HMGCLD disrupts ketogenesis and β-oxidation, leading to energy failure during fasting or stress, with clinical episodes characterized by hypoglycemia, hyperammonemia, lactic acidosis, and encephalopathy. Only 211 cases have been reported worldwide, with no prior reports on anesthetic management in these patients. Clinical features: We report a 14.5-year-old girl with known HMGCLD who was admitted with abdominal pain and nausea following a fatty meal. Imaging confirmed acute cholecystitis. Initial conservative management failed due to persistent vomiting and inability to tolerate feeding. Deviation from the metabolic protocol led to lactic acidosis and hypoglycemia, requiring intensive care with bicarbonate, carnitine, and glucose infusion. Once optimized, she underwent emergency laparoscopic cholecystectomy under sevoflurane-based anesthesia. Propofol was avoided given the patient’s compromised lipid metabolism. Intraoperative glucose and acid-base status were closely monitored, with balanced dextrose-based fluids. The patient remained hemodynamically stable throughout and was discharged three days postoperatively. Conclusions: This case highlights the anesthetic challenges of HMGCLD, where system-level miscommunication can trigger severe metabolic decompensation. A review of the literature emphasizes fasting avoidance, continuous glucose supplementation, careful drug and fluid selection, and multidisciplinary coordination. This report provides the first anesthetic roadmap for HMGCLD, underscoring the need for individualized care and meticulous perioperative metabolic control.

Abstract: Background: Deep gluteal syndrome (DGS) is an underdiagnosed cause of sciatica-like pain, involving the entrapment of the sciatic nerve by various structures within the subgluteal space. While muscular and fibrovascular causes are well-documented, ligamentous pathologies, particularly calcification, remain an unexplored etiology. This case report presents the first documented instance of sacrospinous ligament (SSL) calcification identified as the primary cause of DGS and its successful management with ultrasound-guided prolotherapy. Case Presentation: A 51-year-old female presented with severe, worsening left-sided sciatica of several months' duration. Physical examination revealed an antalgic gait, positive sacroiliac joint tests, and multiple positive DGS-specific provocative tests (FAIR, Pace sign, Seated Piriformis Stretch). Radiographs and musculoskeletal ultrasound (MSK-US) confirmed calcification within the left sacrospinous ligament, with associated sciatic nerve swelling. The patient underwent three sessions of ultrasound-guided prolotherapy (dextrose 10% with lidocaine) targeting the calcification site, followed by a structured rehabilitation program. Results: The patient reported a significant reduction in pain, from a Visual Analog Scale (VAS) score of 10/10 to 1/10 within one month. All previously positive provocative tests converted to negative, indicating a resolution of the nerve entrapment. Functional mobility was fully restored. Conclusions: This case highlights sacrospinous ligament calcification as a novel and previously unreported pathological entity responsible for deep gluteal syndrome. To our knowledge, this is the first report to implicate ligamentous calcification as a primary etiological factor in DGS. Musculoskeletal ultrasound proved indispensable for both diagnosis and treatment guidance. Furthermore, ultrasound-guided prolotherapy emerged as a successful and minimally invasive therapeutic option in this case, potentially by stabilizing the ligament and reducing neurogenic inflammation. This case expands the differential diagnosis of sciatica, introduces a new target for intervention in refractory cases, and underscores the need for future studies in larger patient cohorts to validate these findings.

Abstract: Background/Objectives: Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials (69%), spanning 1996–2024. Local anesthetics (46%) were the most frequent drug class, followed by opioids (19%), corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, 85% of studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies.