BACKGROUND:Chronic pain affects approximately 20% of US adults and often requires multiple treatment modalities. Although many therapies are available, less is known about which treatments patients perceive as helpful in real-world settings. METHODS:This retrospective cohort study analyzed intake questionnaire data from 226 patients evaluated at a multidisciplinary pain clinic between January 2023 and March 2024. Patients rated 56 pain treatments as helpful, unhelpful, never tried, or not sure. Helpfulness was calculated as the proportion of "helpful" responses among patients who tried each treatment. Logistic regression models examined predictors of helpfulness for treatments with helpfulness estimates ≥50% and key covariates were conducted for the seven most helpful treatments. RESULTS:Patients had a mean age of 45.1 ± 15.6 years, and 81.4% were female. The most frequently tried treatments were acetaminophen (90%), physical therapy (88%), and ibuprofen (83%). Treatments with helpfulness estimates ≥50% included massage therapy (77% [70%, 84%]), oxycodone (74% [65%, 82%]), psychotherapy (67% [58%, 77%]), hydromorphone (67% [54%, 79%]), physical therapy (62% [55%, 68%]), aquatic therapy (62% [50%, 73%]), and hydrocodone (61% [53%, 70%]). CONCLUSION:Patient-reported helpfulness varied across treatments, supporting multidisciplinary, patient-centered chronic pain care.
BACKGROUND:Erythromelalgia (EM) is a rare, debilitating condition characterized by episodic burning pain, erythema, and increased skin temperature, typically affecting the distal extremities. EM significantly impairs quality of life (QoL) and may lead to functional disability. Although its pathophysiology is not fully understood, proposed mechanisms include small fiber nerve dysfunction and dysregulation of the sympathetic nervous system. Management remains challenging, with no universally effective treatment currently available. CASE PRESENTATION:We present three patients with refractory lower extremity erythromelalgia treated with lumbar sympathetic block (LSB). All patients had chronic treatment-refractory symptoms and had failed multiple prior treatments, including neuropathic medications and conservative measures. Bilateral L3 LSBs were performed using a standardized approach. Two patients experienced substantial symptom improvement, with reported reductions in pain intensity and a prolonged benefit lasting several months. One patient demonstrated partial, short-term improvement. Repeated LSB procedures were performed in cases of symptom recurrence. CONCLUSION:In this retrospective case series, LSB was associated with symptomatic improvement in selected erythromelalgia patients, potentially by modulating sympathetic activity and regional blood flow. However, given the small sample size and retrospective design, no conclusions regarding efficacy can be drawn. Further studies are needed to better define patient selection criteria and long-term outcomes.
AIM:This study evaluated the efficacy of intravenous ketamine for chronic neuropathic pain through a systematic review and meta-analysis of randomized clinical trials. METHODS:Searches were conducted in PubMed, Cochrane CENTRAL, and EMBASE until March 2026 in accordance with the PRISMA framework: adult patients with chronic neuropathic pain, intravenous ketamine as the intervention, placebo as the comparator, and pain relief outcomes. RESULTS:Fifteen randomized clinical trials (n = 251) were included in the systematic review, of which six trials (n = 135) were included in the primary outcome meta-analysis. Ketamine doses ranged from 60 µg/kg to 1 mg/kg. Pooled analysis showed that intravenous ketamine was superior to placebo in achieving a ≥50% reduction in pain intensity (RR = 2.79, 95% CI: 1.47-5.30; I2 = 28.3%), with a more pronounced effect in studies using a standardized dose of 400 µg/kg (RR = 5.68; 95% CI: 2.02-15.99; I2 = 0%). However, ketamine was associated with a higher incidence of adverse effects compared to placebo (RR = 3.27; 95% CI: 2.20-4.84; I2 = 20.1%). CONCLUSION:Overall, intravenous ketamine demonstrates the potential to provide effective short-term pain relief. Although adverse events were more frequent, they were generally mild and transient. Methodological heterogeneity and small sample sizes limit the generalizability of these findings.Protocol registration: The www.crd.york.ac.uk/prospero identifier is CRD42021229758.
OBJECTIVE:To synthesize evidence on TENS efficacy for primary dysmenorrhea, providing quantitative meta-analysis of pain intensity, exploratory subgroup analyses on electrode placement, and systematic RoB 2 assessment, addressing gaps from previous qualitative reviews. METHOD:Systematic search across PubMed, VHL, Web of Science, Embase, LILACS, PEDro, and gray literature, without restrictions. RoB 2 was applied independently by two reviewers. Primary outcome: pain intensity. Meta-analysis used RevMan 5.4.1. RESULTS:Eight studies included from 1,018 records. TENS significantly reduced pain (SMD = -1.85; 95% CI -2.90 to -0.79; p < 0.001), with high heterogeneity (I2 = 94%). Subgroup analyses showed significant effects regardless of application site. . CONCLUSION:This meta-analysis quantifies TENS analgesic effect for primary dysmenorrhea, suggesting pain reduction irrespective of electrode placement. However, very high heterogeneity, moderate-to-high risk of bias, wide parameter variability, small samples, and imprecise subgroup estimates limit certainty. TENS appears safe (no serious adverse events), but underreporting prevents firm conclusions. Standardized protocols and high-quality, low-bias trials are needed. Certainty is likely low per GRADE considerations. PROTOCOL REGISTRATION:www.crd.york.ac.uk/prospero identifier is CRD42024540314.
INTRODUCTION:Coccydynia is characterized by persistent tailbone pain that significantly impairs quality of life. Despite conservative treatments, many patients experience inadequate symptom relief. Prolotherapy, a regenerative injection technique for chronic musculoskeletal pain, shows promise; however, its efficacy for coccydynia has not been evaluated in controlled comparative studies. To the best of the authors' knowledge, this is among the first such studies. AREAS COVERED:This retrospective comparative study evaluated 56 patients with primary chronic coccydynia refractory to conservative management. Twenty-nine patients received ultrasound-guided 10% dextrose prolotherapy combined with therapeutic exercises and patient education; 27 patients received exercises and education alone. Mean pain duration was 20.7 ± 17.3 months (prolotherapy) and 26.9 ± 17.3 months (control). Primary outcomes were pain intensity and functional disability at baseline, 1-month, and 3-month follow-up. Secondary outcomes comprised the Paris Functional Coccydynia Impact Questionnaire. EXPERT OPINION:Ultrasound-guided dextrose prolotherapy combined with therapeutic exercises demonstrated superior efficacy compared to exercises alone. The prolotherapy group achieved a 73% pain reduction at 3 months versus 26% in controls. An 82.8% clinical response rate and 37.9% complete pain resolution were observed, with a favorable safety profile. These results support prolotherapy as an effective, minimally invasive option for chronic coccydynia following failed conservative management.
Kienböck's disease (KD), an avascular necrosis of the lunate bone, is a rare and progressive condition that may lead to chronic wrist pain and functional limitation. While avascular necrosis associated with COVID-19 has been reported in other skeletal sites, involvement of the lunate bone has not previously been reported. This case adds novel evidence that suggests a potential association between COVID-19 and Kienböck's disease. To demonstrate this potential association, this paper reports a case of Kienböck's disease developing following COVID-19 infection in a 50-year-old woman who was hospitalized in August 2020 with PCR-confirmed COVID-19 pneumonia and bilateral ground-glass opacities on chest CT. She had no prior corticosteroid exposure or comorbidities. Approximately 12 weeks after recovery, she developed progressive left wrist pain without any history of trauma. Subsequent imaging demonstrated avascular necrosis of the lunate bone. Interventions included autologous cytokine-rich serum injections, pharmacological pain management, and ultimately surgical lunate excision with bone grafting due to progression of the disease. This case represents the first reported instance of Kienböck's disease developing after COVID-19 infection. Increased clinician awareness may lead to earlier diagnosis and better functional outcomes.
INTRODUCTION:Schizophrenia is a chronic and disabling neuropsychiatric disorder traditionally defined by psychotic and cognitive symptoms. Increasing evidence suggests that neuroinflammatory mechanisms contribute to its pathophysiology and may also underlie common but underrecognized somatic manifestations. These include altered pain perception, characterized by both diminished sensitivity and chronic pain, with important implications for functional outcomes and rehabilitation. AREAS COVERED:This narrative review examines clinical, preclinical, and translational studies addressing the role of neuroinflammation in schizophrenia, with a specific focus on microglial and astrocytic activation, cytokine signaling, oxidative stress pathways, and their interactions with central pain processing circuits. The review was informed by targeted searches of PubMed, Scopus, Web of Science, and Google Scholar, covering articles published from database inception to January 2026, with emphasis on studies relevant to pain modulation, symptom expression, and neurobiological heterogeneity in schizophrenia. EXPERT OPINION:Neuroinflammation represents a biologically plausible link between core schizophrenia pathology and altered pain perception. Recognition of pain as an integrated component of disease biology, rather than a secondary complaint, may improve clinical assessment and treatment planning. Investigating and targeting neuroinflammatory pathways holds promise for personalized interventions that address neuropsychiatric symptoms and pain, potentially enhancing rehabilitation outcomes and quality of life.
Chronic pain (CP) affects an important proportion of the global population, imposing a significant socio-economic burden and serving as a leading cause of disability. While the biopsychosocial approach is the gold standard for treatment, many patients fail to receive adequate care due to healthcare resource constraints. Effective management requires a comprehensive assessment. However, traditional questionnaires often miss the subjective and multidimensional depth of the pain experience. Differently, written narratives (WNs) empower patients to describe their pain in their own words. Nevertheless, qualitative analysis, such as WN, is often time-consuming for clinicians.This paper explores how Large Language Models (LLMs) can facilitate clinicians in analyzing WNs. Evidence from the AINarratives project and other emerging studies indicates that LLMs can evaluate pain narratives with accuracy and utility comparable to human experts, identifying biopsychosocial themes that correlate with standardized clinical scores.We conclude that LLMs should serve as clinical companions rather than substitutes, streamlining qualitative data processing to enhance the clinician-patient interaction and facilitate personalized care.
Postpartum pain remains a significant yet under-addressed issue in low- and middle-income countries (LMICs), where pharmacological analgesia may be limited by availability, side effects, and breastfeeding safety concerns. This systematic review aimed to synthesize and critically appraise the clinical trial evidence on the effectiveness of acupressure for managing postpartum pain in LMIC settings. Following PRISMA 2020 guidelines, searches were conducted in PubMed, Cochrane Library, ScienceDirect, Taylor & Francis, ProQuest, and Google Scholar for studies published between 2015 and 2025. Nine eligible studies from Turkey, Iran, Taiwan, Thailand, and Indonesia were included and appraised using the CASP tool. Most studies focused on the immediate/acute postpartum phase, while a few extended into the early postpartum period. Across various postpartum pain conditions, most included studies reported reductions in pain intensity following body or auricular acupressure compared with usual care, sham, or comparator interventions. Several studies also reported additional benefits, such as decreased analgesic consumption after cesarean delivery and improvements in functional limitations and depressive symptoms. Overall, acupressure may serve as a low-cost adjunct for postpartum pain management in resource-limited maternity services. Nevertheless, protocol variability and short follow-up periods highlight the need for larger multicentre trials with standardized dosing and broader maternal outcomes.
AIM:Psychiatric and medical comorbidities are common in migraine and worsen pain burden and treatment outcomes. We examined the prevalence of comorbidities overall, before and during the COVID-19 pandemic, across migraine subtypes, and identified associated risk factors. METHODS:This retrospective comparative cohort study included patients diagnosed with migraine according to the International Classification of Headache Disorders at a tertiary headache center in Thailand. Clinical data were obtained from standardized case record forms and electronic medical records. Comorbidities were self-reported at the initial visit and verified by documented diagnoses. Group differences were analyzed using chi-square or independent t-tests. Multivariable logistic regression identified independent risk factors. RESULTS:Of the 572 patients, 29.9% had migraine with aura. Overall, 67.7% had at least one comorbidity, and 8.0% had psychiatric comorbidities. During the COVID-19 pandemic, overall and psychiatric comorbidities were more prevalent than in the pre-2020 period (79.4% vs. 66.2% and 17.4% vs. 6.9%, respectively). Chronic migraine was independently associated with comorbidities (adjusted OR 1.67, 95% CI 1.11-2.51), whereas the pre-COVID-19 period was associated with lower odds. CONCLUSIONS:Comorbidities are highly prevalent in migraine, particularly during the COVID-19 pandemic and among patients with chronic migraine. Integrated pain management and routine psychiatric screening may improve comprehensive care.
Ketamine is a noncompetitive antagonist of the N-methyl-D-aspartate receptor that has garnered significant interest as a treatment for both chronic pain and mental health symptoms in the last two decades. The authors introduce the methodological framework of the Ketamine Infusion Pain Program (KIPP) at Toronto Western Hospital (TWH) and outline a high dose ketamine infusion (HDKI) regimen for refractory pain syndromes implemented through an innovative multidisciplinary care model. HDKIs have been offered at TWH since 2010 and in 2023, the KIPP was formally established and reconceptualized to include multidisciplinary services. The redesign included peri-ketamine psychology services to provide education, support, and post-ketamine integration, and to optimize adaptive behaviors in the post-ketamine period. At KIPP, ketamine (0.5 mg.kg-1) is provided intravenously as a bolus, followed by an infusion dose up to 1 mg-1.kg.hr-1 IV for six hours. The KIPP is collecting data on pain, psychological factors, sleep, and functioning pre- and post-HDKI to evaluate patient outcomes, which will be presented in a future article. Future directions include further refinement of dosing protocols and co-administration of other medications and the expansion of peri-infusion psychology services with increased focus on preparation and integration, as well as the evaluation of these initiatives.
AIMS:Thoracic surgery is associated with severe acute and chronic pain, high opioid use, and other adverse outcomes. Gabapentin is commonly used perioperatively, but its effectiveness remains uncertain. This systematic review and meta-analysis evaluated the efficacy and safety of perioperative gabapentin versus placebo after thoracic surgery. PATIENTS AND METHODS:Cochrane, Embase, PubMed, and Web of Science were searched through 29 August 2025 for randomized controlled trials comparing gabapentin with placebo in adults undergoing thoracic surgery. The primary outcome was pain at 24 hours. Secondary outcomes included pain at other time points, opioid consumption, chronic pain, and adverse events. Data were pooled using random-effects models. RESULTS AND CONCLUSIONS:Six trials including 748 patients were analyzed. Gabapentin had no significant effect on rest pain at 24 hours (MD -0.13; 95% CI -1.17 to 0.91). A non-significant trend toward worse cough-evoked pain at 24 hours was observed with gabapentin (MD 0.53; 95% CI 0.00 to 1.07). Gabapentin also did not significantly affect opioid consumption, pain chronification, or adverse events such as nausea, sedation, or delirium. Based on low-certainty evidence, perioperative gabapentin does not appear to provide meaningful benefit after thoracic surgery. PROTOCOL REGISTRATION:The www.crd.york.ac.uk/prospero identifier is CRD420251136259.
OBJECTIVE:This systematic review and meta-analysis evaluated the effectiveness of craniocervical flexor (CCF) exercises on pain intensity, functional disability, muscle endurance, muscle strength, cervical flexion range of motion, and craniovertebral angle (CVA) in patients with chronic neck pain (CNP). METHODS:Twenty-five randomized controlled trials (1,166 participants) were included. Methodological quality was assessed using the PEDro scale, and risk of bias via the RoB 2 tool. Meta-analysis was performed using standardized mean differences (SMD) from random effects models. RESULTS:Compared to other interventions, CCF exercises produced a moderate-to-large reduction in pain (SMD: -0.97) and moderate improvement in disability (SMD: -0.50). Combining CCF with other interventions yielded a very large pain reduction (SMD: -1.70). Muscle endurance showed a very large increase (SMD: 1.55), muscle strength a moderate increase (SMD: 0.60), cervical flexion range of motion substantial improvement (SMD: 0.83), and CVA moderate improvement (SMD: 0.51). CONCLUSION:CCF exercises, alone or combined, appear to improve pain, function, and forward head posture in CNP. However, due to substantial heterogeneity, variable risk of bias, and diverse protocols, findings are suggestive rather than definitive. Higher-quality RCTs with standardized protocols are needed to confirm these clinically promising results. PROTOCOL REGISTRATION:www.crd.york.ac.uk/prospero identifier CRD420251176050.
Chronic pain represents a major clinical and public health challenge due to its multidimensional nature and frequent resistance to treatment. Beyond the traditional distinction between nociceptive and neuropathic pain, increasing evidence highlights central sensitization as a key transdiagnostic mechanism underlying pain persistence, symptom severity, and reduced treatment response. However, longitudinal studies integrating neurophysiological, cognitive, psychological, and behavioral dimensions across different chronic pain phenotypes remain limited. This study describes a prospective, longitudinal observational protocol aimed at investigating central sensitization in patients with nociceptive, neuropathic, and mixed chronic pain. Participants will be assessed at baseline and at 12-month follow-up using both psychometric and neurophysiological measures, including the Central Sensitization Inventory and laser-evoked potentials, together with standardized evaluations of pain intensity, cognitive functioning, psychological distress, pain self-efficacy, patient engagement, and medication adherence. By combining subjective and objective measures of central sensitization within a multidimensional framework, this study aims to improve the characterization of chronic pain phenotypes and to support a more precise, mechanism-based, and personalized approach to pain management in clinical practiceClinical trial registration: The http://www.ClinicalTrials.gov identifier is NCT07321080.
Injection granulomas (IGs) are recognized as a consequence of the injection of injectates into adipose tissue after routine drug or vaccine injections without reaching the muscular tissue. A series of reactions of the injectates in adipose tissue results in necrotic tissue and deposition of calcium crystals. IGs are usually asymptomatic but may rarely be symptomatic. In the past, symptomatic cases were mostly managed conservatively or surgically. However, to the best of our knowledge, no procedure other than surgical or conservative treatment has been reported. A 57-year-old patient with a history of multiple intramuscular diclofenac injections presented with localized right buttock pain for 8 months. The patient, who did not respond to conservative treatment, underwent an ultrasound-guided barbotage procedure commonly used in the diagnosis of calcific periarthritis. The patient's pain complaint was evaluated according to the visual analog scale (VAS). The patient reported VAS:7 before the barbotage procedure and VAS:2 at the sixth week follow-up after the barbotage procedure. This case report, provided that it is supported by future studies, suggests that the ultrasound-guided barbotage procedure, which is commonly used in patients with calcific periarthritis, may be a promising treatment method in IG cases unresponsive to conservative treatment.
BACKGROUND:Chronic non-cancer pain and opioid use disorder (OUD) are common co-morbidities. Clinical guidelines and regulatory changes have created challenges for providers and programs in which chronic pain and OUD treatment may be sub-optimally integrated for patients receiving long-term opioid therapy (LTOT). METHODS:We identified a cohort of 61 patients in HIV primary care who met criteria for LTOT (i.e. prescribed opioids for chronic non-cancer pain >90 days) and who experienced disruptions in pain management and present an analytic case study. A multidisciplinary team developed a two-step intervention to mitigate withdrawal and overdose risk and to facilitate ongoing safe, effective pain management. RESULTS:Among 61 patients, 29.5% were receiving methadone for pain and 9.8% were receiving LTOT for pain while enrolled in methadone OUD treatment programs. All 61 LTOT patients were referred for pain management reassessment. The following assessments were made: 24.6% had chronic pain without OUD; 9.8% had OUD and transitioned to OUD treatment; 3.3% self-elected to stop opioids; 29.5% were consensually initiated on a slow consensual opioid tapering schedule. CONCLUSIONS:A multidisciplinary intervention can provide overdose risk mitigation, facilitate pain and OUD re-assessments and can guide ongoing management of cohorts of patients previously maintained on LTOT for chronic non-cancer pain.
OBJECTIVE:To investigate the relationship between clinical pain and functional mobility, especially gait performance, in individuals with Parkinson's Disease (PD). METHOD:Pain was evaluated using the Brief Pain Inventory (BPI), while functional mobility was measured through the Timed Up and Go (TUG), Six-Minute Walk Test (6MWT) distance and Freezing of Gait Questionnaire (FOGQ) total score. RESULTS:Thirty-four individuals with PD were assessed during the "ON" medication state. While reported pain intensity was low, pain interference was moderate and significantly correlated with reduced walking performance and greater freezing of gait severity (p < 0.05, ρ=0.37). Notably, higher pain interference, but not intensity, was associated with shorter 6MWT distances (p < 0.01, ρ=-0.48) and more frequent freezing episodes (p < 0.001, ρ=0.64). Another test, the TUG was not affected by pain. CONCLUSION:Assessing pain interference, rather than pain intensity alone, is essential when addressing functional mobility in PD. Pain interference is significantly related to reduced gait performance and increased freezing, highlighting the importance of rehabilitation strategies that focus on minimizing disruptive impact of pain on movement.
Acute musculoskeletal (MSK) pain remains a leading contributor to global disability, with little reduction in its burden over the past three decades. Despite increasing recognition of the prognostic role of psychological comorbidities such as anxiety, depression, and stress, clinical care for MSK pain continues to prioritize biomedical interventions, often at the expense of psychosocial considerations. This disconnect is particularly evident in emergency department (ED) settings, where care pathways focus on immediate physical assessment and discharge planning, with limited integration of mental health screening or support. Individuals presenting with acute MSK pain and comorbid mental health conditions may therefore experience fragmented care, increasing their risk of chronicity and suboptimal outcomes. This narrative review synthesizes current evidence on clinical care pathways for individuals presenting to EDs with acute MSK pain in the context of preexisting mental health disorders. It highlights the limitations of existing models of care, underscores the need for integrated biopsychosocial approaches, and identifies opportunities for improving patient-centered outcomes through more holistic and prognostically informed care strategies.
BACKGROUND:Neuropathic orofacial pain comprises chronic conditions that severely affect daily function, psychological well-being, and quality of life, yet no umbrella review has synthesized how available treatments influence quality-of-life outcomes. OBJECTIVE:To critically summarize evidence from systematic reviews and meta-analyses evaluating the impact of therapeutic interventions on quality-of-life-related outcomes in neuropathic orofacial pain. METHODS:This umbrella review followed Joanna Briggs Institute methodology and PRISMA 2020. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception to 2 January 2026. Eligible studies were systematic reviews/meta-analyses of therapeutic interventions for neuropathic orofacial pain reporting quality-of-life or patient-reported outcomes. Quality was assessed with AMSTAR 2 and ConQual. RESULTS:Seven systematic reviews were included. Overlap was slight (CCA = 2.14%) and disappeared after adjustment (CCA = 0%). Repetitive transcranial magnetic stimulation improved selected patient-reported domains (MD -9.23; 95% CI-11.91 to -6.54). Microvascular decompression showed sustained pain relief, with benefits inferred from satisfaction and functional recovery. Pulsed radiofrequency improved short-term pain/sleep outcomes. Botulinum toxin type A reduced pain but not broader quality-of-life domains. CONCLUSIONS:These interventions may improve quality-of-life-related outcomes when pain control is sustained, but evidence remains indirect and methodologically limited. PROTOCOL REGISTRATION:PROSPERO, http://www.crd.york.ac.uk/prospero, identifier CRD420251276623.
