{"title":"Acupotomy Alleviates Pain and Attenuates Spinal Neuronal Hyperexcitability in Knee Osteoarthritis Rats: Implication of the CaMKII/GluA1 Axis.","authors":"Meng Wu, Jinyan Teng, Ziyi Huang, Ruizhe Xu, Xiaoming Gao, Xin Hao, Zhigang Li, Zhaoheng Liu","doi":"10.2147/JPR.S633426","DOIUrl":"https://doi.org/10.2147/JPR.S633426","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the spinal mechanisms underlying the analgesic effects of acupotomy on chronic pain and central sensitization in rats with monosodium iodoacetate (MIA)-induced knee osteoarthritis (KOA).</p><p><strong>Methods: </strong>Following MIA-induced KOA and a three-week acupotomy intervention in rats, pain behaviors and joint pathology were assessed. Spinal RNA-sequencing was performed to identify differentially expressed genes. Key targets (CaMKII and GluA1) were validated at both mRNA and protein levels using RT-qPCR and Western blotting. Furthermore, immunofluorescence and whole-cell patch-clamp electrophysiology were employed to evaluate the activation and excitability of spinal substantia gelatinosa (SG) neurons.</p><p><strong>Results: </strong>Acupotomy significantly alleviated mechanical and thermal hyperalgesia and reduced joint degeneration in KOA rats. RNA-seq analysis revealed the modulation of 220 genes in the spinal cord. These DEGs were significantly enriched in calcium signaling and synaptic transmission pathways, highlighting <i>CaMKII</i> and <i>Gria1</i> as potential key molecules. Molecular validations confirmed that acupotomy downregulated <i>CaMKII</i> and <i>Gria1</i> mRNA expression and the phosphorylation ratios of CaMKII and GluA1. Furthermore, acupotomy reduced the activation of p-CaMKII-positive neurons in the spinal SG region and dampened their abnormally high-frequency action potential discharges.</p><p><strong>Conclusion: </strong>Acupotomy intervention ameliorates peripheral joint degeneration and exerts significant analgesia in KOA, which is accompanied by a reduction in the intrinsic hyperexcitability of spinal SG neurons. Although direct causal validation utilizing targeted inhibitors is warranted, our findings suggest that this analgesic effect is closely associated with the downregulation of the CaMKII/GluA1 signaling axis, providing a plausible central mechanistic framework.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"633426"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-15eCollection Date: 2026-01-01DOI: 10.2147/JPR.S660740
Ying Ye, Jin Hu
{"title":"Methodological Caveats, Statistical Multiplicity, and Conceptual Dichotomy in Myofascial Trigger Point-Augmented Acupuncture for Knee Osteoarthritis [Letter].","authors":"Ying Ye, Jin Hu","doi":"10.2147/JPR.S660740","DOIUrl":"10.2147/JPR.S660740","url":null,"abstract":"","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"660740"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-15eCollection Date: 2026-01-01DOI: 10.2147/JPR.S650628
Yi Xiang, Zengao Lu, Liang Li, Tonggang Fan
{"title":"Effects of Mind-Body Exercises on Pain Intensity in Individuals with Chronic Nonspecific Low Back Pain: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.","authors":"Yi Xiang, Zengao Lu, Liang Li, Tonggang Fan","doi":"10.2147/JPR.S650628","DOIUrl":"https://doi.org/10.2147/JPR.S650628","url":null,"abstract":"<p><strong>Objective: </strong>To synthesize the effects of mind-body exercises (MBEs) on pain in adults with chronic nonspecific low back pain (CNLBP) and assess whether comparative and study-level dose evidence can inform exercise selection.</p><p><strong>Methods: </strong>We searched 10 databases from inception to 11 July 2026 for randomized controlled trials. Random-effects pairwise meta-analysis compared MBEs with control conditions. Network meta-analysis (NMA) compared yoga, Pilates, Tai Chi (TC), and qigong. Exploratory subgroup analyses and meta-regression evaluated intervention duration, frequency, session duration, weekly exercise volume, and comparator type. Risk of bias and certainty of evidence were assessed using the Cochrane Risk of Bias 2 tool (RoB 2) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, respectively.</p><p><strong>Results: </strong>Twenty-five randomized controlled trials were included. MBEs reduced pain on a 0-10-cm visual analog scale compared with control conditions (mean difference, -1.56 cm; 95% confidence interval, -1.98 to -1.15). Heterogeneity was substantial, with an I-squared statistic of 92.7%, and the 95% prediction interval ranged from -3.69 to 0.56 cm. No statistically significant subgroup differences were identified for intervention duration, frequency, session duration, or weekly exercise volume. Comparator type was associated with study-level effect estimates (<i>P</i> = 0.0036). In the NMA, all four MBEs had lower estimated pain scores than the control node, but no between-modality differences were detected. TC had the highest surface under the cumulative ranking curve (SUCRA) value (85.4%). The certainty of evidence was low for all network comparisons assessed.</p><p><strong>Conclusion: </strong>MBEs may reduce pain intensity in adults with CNLBP. However, substantial heterogeneity, uncertainty in transitivity, and low certainty of evidence limit confidence in comparative estimates. The available evidence does not establish a preferred MBE modality or an optimal exercise dose.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"650628"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-15eCollection Date: 2026-01-01DOI: 10.2147/JPR.S628598
Diana S Meske, Robert H Dworkin, Jeffrey Gudin, Nebojsa Nick Knezevic, Mark J Jaros, Kip Vought, Dmitri Lissin, Nathaniel Katz
{"title":"Evaluating IMMPACT Criteria for the Clinical Meaningfulness of Between-Group Differences: Interpreting Randomized Trial Results within a Context of Existing Chronic Pain Analgesics.","authors":"Diana S Meske, Robert H Dworkin, Jeffrey Gudin, Nebojsa Nick Knezevic, Mark J Jaros, Kip Vought, Dmitri Lissin, Nathaniel Katz","doi":"10.2147/JPR.S628598","DOIUrl":"https://doi.org/10.2147/JPR.S628598","url":null,"abstract":"<p><p>The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has published methods and consensus benchmarks for determining the clinical meaningfulness of analgesic clinical trial results. However, results are commonly misinterpreted when within-subject thresholds for clinical meaningfulness are applied to between-group differences (ie, active vs placebo). IMMPACT has emphasized that between-group differences must be interpreted on a case-by-case basis and previously published a qualitative framework that is informed by quantitative analyses, drawing on data from within an individual study together with external sources. We tested this framework by applying it to a recently completed Phase 3 clinical study (the CLEAR Trial), which assessed the efficacy and safety of SP-102-a viscous dexamethasone product for transforaminal (TF) epidural administration-versus placebo for the treatment of lumbosacral radicular pain (LRP). To contextualize the efficacy results, we conducted a narrative review and comparative analysis of all FDA-approved pharmaceutical products for chronic pain conditions and of off-label TF steroid injection studies. This article presents conclusions regarding both the utility of the IMMPACT framework and the clinical meaningfulness of the results of the example trial. Implementing the framework was generally straightforward, although it required user discretion in several areas and exposed several limitations within both the framework itself and the underlying clinical study data. Based on the IMMPACT framework, SP-102 appears to provide a clinically meaningful benefit in between-group comparisons.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"628598"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-14eCollection Date: 2026-01-01DOI: 10.2147/JPR.S630567
Hongzhuan Chen, Maoxin Xiao, Hong Li, Pengcheng Zhang, Jin Zhang
{"title":"Effects of an Esketamine-Containing Induction Regimen on Postoperative Sleep, Analgesia, and Postpartum Depression in Parturients with Sleep Disorders Undergoing Cesarean Section Under General Anesthesia: A Double-Blind Randomized Trial.","authors":"Hongzhuan Chen, Maoxin Xiao, Hong Li, Pengcheng Zhang, Jin Zhang","doi":"10.2147/JPR.S630567","DOIUrl":"10.2147/JPR.S630567","url":null,"abstract":"<p><strong>Background: </strong>Preoperative sleep disturbances in parturients undergoing cesarean section correlate with exacerbated postoperative pain and an elevated risk of postpartum depression. Although esketamine demonstrates analgesic and antidepressant benefits in the general cesarean population, its combined effects on sleep, analgesia, and mood remain poorly characterized in patients with pre-existing sleep impairment. This study investigated the efficacy of an esketamine‑containing induction regimen on postoperative sleep quality, analgesia, and early depressive symptoms in parturients with PSQI‑defined preoperative sleep disorders scheduled for elective cesarean section under general anesthesia.</p><p><strong>Methods: </strong>We conducted a randomized, double-blind, placebo-controlled trial involving 90 parturients scheduled for elective cesarean section under general anesthesia. Participants were randomly allocated in a 1:1 ratio to receive either an esketamine-containing induction regimen (esketamine 0.25 mg/kg plus propofol 1.0 mg/kg; n=45) or a standard induction regimen (saline plus propofol 2.0 mg/kg; n=45). All 90 participants were included in the intention-to-treat analysis (missing data imputed), and 84 (41 vs 43) were included in the complete-case sensitivity analysis. The primary outcome was sleep quality on postoperative day (POD) 1, assessed using an 11-point sleep Numerical Rating Scale (NRS; 0=best, 10=worst; 24-hour recall). Secondary outcomes included sleep NRS scores on POD 3 and POD 42, and the Pittsburgh Sleep Quality Index (PSQI) on POD 42 (exploratory); Visual Analog Scale (VAS) pain scores at 2, 12, 24, and 48 hours, and rescue analgesic consumption over 72 hours; and Edinburgh Postnatal Depression Scale (EPDS) scores on POD 3 and POD 42 (≥13 indicating a positive result).</p><p><strong>Results: </strong>The esketamine regimen significantly improved the primary outcome (sleep NRS on POD 1; mean difference [MD] = 3.0, 95% CI: 2.0 to 4.0; P < 0.001). Exploratory secondary outcomes showed early pain benefits and reduced rescue analgesia (risk ratio [RR] = 3.33, 95% CI: 0.98 to 11.32; absolute risk difference = 15.5%, 95% CI: 0.7% to 30.21%), but these differences were small with wide intervals. Continuous EPDS scores were lower on POD 3 (P = 0.004), while the exploratory binary analysis (EPDS ≥ 13) was not significant (RR = 1.22, 95% CI: 0.56 to 2.66; P = 0.613). No serious adverse events occurred; however, the trial was not powered for safety outcomes.</p><p><strong>Conclusion: </strong>An esketamine-containing induction regimen was associated with improved early sleep quality on POD 1 in parturients with preoperative sleep disorders undergoing cesarean delivery under general anesthesia. However, because the trial was not powered for secondary outcomes or safety, and the differing propofol doses prevent isolation of esketamine's specific effect, these secondary findings are exploratory. Further adequately powere","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"630567"},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-14eCollection Date: 2026-01-01DOI: 10.2147/JPR.S645744
Jung-Gyung Lee, Sun-Young Park, Bong-Jin Shin, Yoomin Choi, Bok-Nam Seo, Ojin Kwon, Eui-Hyoung Hwang
{"title":"Effectiveness and Safety of Ultrasound-Guided Pharmacopuncture for Carpal Tunnel Syndrome: Protocol for A Multicenter, Randomized, Assessor-Blinded, Waiting-List-Controlled Clinical Trial.","authors":"Jung-Gyung Lee, Sun-Young Park, Bong-Jin Shin, Yoomin Choi, Bok-Nam Seo, Ojin Kwon, Eui-Hyoung Hwang","doi":"10.2147/JPR.S645744","DOIUrl":"10.2147/JPR.S645744","url":null,"abstract":"<p><strong>Introduction: </strong>Carpal tunnel syndrome (CTS) is a common compressive neuropathy caused by entrapment of the median nerve within the carpal tunnel. Although conventional treatments such as injections and surgery are used, Korean medicine interventions, including pharmacopuncture, are also used in clinical practice. However, clinical evidence from randomized controlled trials of pharmacopuncture for CTS remains limited. Ultrasound-guided pharmacopuncture may improve procedural precision by enabling real-time identification of the median nerve and surrounding anatomical structures.</p><p><strong>Objective: </strong>To evaluate the effectiveness and safety of a pragmatic ultrasound-guided pharmacopuncture as an additional treatment to lifestyle management and exercise education in patients with carpal tunnel syndrome.</p><p><strong>Methods and analysis: </strong>This is a multicenter, randomized, assessor-blinded, waiting-list-controlled clinical trial registered with the Clinical Research Information Service (CRIS; KCT0011180). A total of 64 participants with clinically diagnosed CTS will be enrolled at two Korean medicine hospitals and randomly allocated in a 1:1 ratio to either the intervention group or the waiting-list control group. The intervention group will receive ultrasound-guided pharmacopuncture once weekly for 3 weeks in addition to lifestyle management and exercise education, whereas the waiting-list control group will receive lifestyle management and exercise education only during the study period. The primary outcome is the change in hand numbness and pain visual analog scale score from baseline to Visit 4 (Week 4). Secondary outcomes include the Boston Carpal Tunnel Questionnaire, median nerve cross-sectional area measured by ultrasound, maximum grip strength of the affected hand, and Patient Global Impression of Change. The primary effectiveness outcome will be evaluated in the full analysis set using a mixed-effects model for repeated measures.</p><p><strong>Conclusion: </strong>This trial will provide comparative effectiveness and safety evidence for ultrasound-guided pharmacopuncture added to lifestyle management and exercise education in patients with carpal tunnel syndrome.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"645744"},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-14eCollection Date: 2026-01-01DOI: 10.2147/JPR.S633466
Kuo Bi, Xiran Xiao, Bingna Hou, Ruixue Lu, Ruijuan Zhang, Yan Zhang, Di Wang, Xinhua Li, Zhiguo Zhao, Liyun Yang
{"title":"Mild Moxibustion Alleviates Primary Dysmenorrhea in Rats Through TRPV1-Associated Modulation of NF-κB Signaling and Uterine Oxidative Stress.","authors":"Kuo Bi, Xiran Xiao, Bingna Hou, Ruixue Lu, Ruijuan Zhang, Yan Zhang, Di Wang, Xinhua Li, Zhiguo Zhao, Liyun Yang","doi":"10.2147/JPR.S633466","DOIUrl":"10.2147/JPR.S633466","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the therapeutic effect and analgesic mechanism of mild moxibustion at Shenque (CV8) and Guanyuan (CV4) in a primary dysmenorrhea (PD) rat model, focusing on the involvement of TRPV1-NF-κB signaling and uterine oxidative stress.</p><p><strong>Methods: </strong>Forty female Sprague-Dawley (SD) rats were randomly divided into five groups (n=8): blank group (BG), model group (MG), mild moxibustion group (MMG), antagonist capsazepine group (CPZG), and ibuprofen group (IG). PD models were established through cold stimulation combined with estradiol benzoate and oxytocin injection. The MMG received mild moxibustion at \"Shenque\" (CV8) and \"Guanyuan\" (CV4) acupoints. The CPZG was pretreated with capsazepine (CPZ) before moxibustion. The IG received ibuprofen via gavage. After intervention, pain thresholds and writhing scores were measured; uterine pathology was observed via HE staining; ELISA, colorimetric assay, immunohistochemistry (IHC), and Western blotting were used to detect relevant biomarkers.</p><p><strong>Results: </strong>Mild moxibustion significantly elevated pain thresholds and reduced writhing scores (vs MG, <i>P</i><0.01). Capsazepine partially reversed these analgesic effects (vs MMG, <i>P</i><0.01). Mild moxibustion decreased serum IL-1β, TNF-α, and PGF<sub>2α</sub> while increasing PGE<sub>2</sub> (vs MG, <i>P</i><0.01). Mild moxibustion upregulated TRPV1 expression at acupoints (vs MG, <i>P</i><0.01), whereas capsazepine suppressed TRPV1 expression (vs MMG, <i>P</i><0.01). Mild moxibustion downregulated uterine NF-κB P-p65 and COX-2 expression (vs MG, <i>P</i><0.01), while CPZG upregulated these proteins (vs MMG, <i>P</i><0.01). Furthermore, mild moxibustion upregulated uterine SOD2 expression (vs MG, <i>P</i><0.05), decreased MDA content, and increased GSH content and SOD activity (vs MG, <i>P</i><0.05 or <i>P</i><0.01).</p><p><strong>Conclusion: </strong>Mild moxibustion at CV8 and CV4 alleviates PD in rats through mechanisms involving TRPV1 activation, NF-κB pathway modulation, and improvement of uterine oxidative stress. These findings provide a preclinical basis for further investigation.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"633466"},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-14eCollection Date: 2026-01-01DOI: 10.2147/JPR.S651675
Mohammed M Alshehri, Mohammad Abu Shaphe, Rashid Ali Beg, Aafreen Aafreen, Shahul Hameed Pakkir Mohamed, G Shankar Ganesh, Abdur Raheem Khan, Monira I Aldhahi
{"title":"Socio-Demographic Inequalities in the Burden of Low Back Pain Across Development Strata: Sex-Specific, Age-Standardized Trends in Prevalence, Incidence and Disability from the Global Burden of Disease Study 2023, 2003-2023.","authors":"Mohammed M Alshehri, Mohammad Abu Shaphe, Rashid Ali Beg, Aafreen Aafreen, Shahul Hameed Pakkir Mohamed, G Shankar Ganesh, Abdur Raheem Khan, Monira I Aldhahi","doi":"10.2147/JPR.S651675","DOIUrl":"https://doi.org/10.2147/JPR.S651675","url":null,"abstract":"<p><strong>Background: </strong>Low back pain (LBP) is a leading contributor to non-fatal disability and rehabilitation needs worldwide. Monitoring trends across sociodemographic strata is important for understanding whether the disability burden is changing equitably across health systems.</p><p><strong>Purpose: </strong>To examine temporal trends and socio-demographic inequalities in the burden of LBP across Socio-demographic Index (SDI) groups from 2003 to 2023 using Global Burden of Disease Study 2023 estimates.</p><p><strong>Methods: </strong>GBD 2023 estimates for LBP prevalence, incidence and years lived with disability (YLDs) were analysed across High, High-middle, Middle, Low-middle and Low SDI groups. Age-standardized rates, all-age numbers, percentage changes and estimated annual percentage changes were calculated. Sex-specific, age-specific and inequality analyses were conducted. The change in all-age YLDs was also partitioned approximately into demographic (population growth and ageing) and epidemiological (age-standardized rate) components.</p><p><strong>Results: </strong>Age-standardized prevalence, incidence, and YLD rates declined modestly across all SDI groups between 2003 and 2023. The greatest decline in age-standardized YLD rates occurred in High SDI countries (-6.2%), whereas Low-middle SDI countries showed the smallest reduction (-2.5%). Despite declining rates, all-age YLD numbers increased in every SDI group, with the largest increase in Low SDI group (+65.2%). In 2023, High SDI had the highest age-standardized YLD rate, followed by Low SDI. Female YLD rates exceeded male rates in all SDI groups, and age-specific YLD rates rose steadily with age. Demographic change alone would have increased YLDs by 28.4% in High SDI and by 51.6-73.9% in the other groups; falling age-standardized rates offset 28.1% of this demographic increase in High SDI but only 7.1-14.1% elsewhere.</p><p><strong>Conclusion: </strong>The age-standardized rates of LBP declined modestly, but the absolute disability burden increased substantially, particularly in lower-SDI settings. Persistent SDI, sex, and age inequalities indicate the need for scalable, gender-sensitive, and context-responsive rehabilitation services. Outside High SDI settings, improvements in age-standardized rates offset only a small share of demographically driven growth in disability.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"651675"},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-13eCollection Date: 2026-01-01DOI: 10.2147/JPR.S628497
Shan Chen, Yinyan He, Bin Que, Zhipeng Liang, Xin Chen, Sheng Li, Rong Zhou
{"title":"Synergistic Inhibition of Spinal TRPV1 Signaling by Combined Eye Acupuncture and Electroacupuncture Alleviates Inflammatory Pain in a Rat Model of Knee Osteoarthritis.","authors":"Shan Chen, Yinyan He, Bin Que, Zhipeng Liang, Xin Chen, Sheng Li, Rong Zhou","doi":"10.2147/JPR.S628497","DOIUrl":"10.2147/JPR.S628497","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain caused by knee osteoarthritis (KOA) remains inadequately managed by safe, non-pharmacological therapies. Although acupuncture is recommended for KOA pain by clinical guidelines, the efficacy of single-modality acupuncture remains modest, and the synergistic mechanisms of combining different acupuncture modalities are poorly understood.</p><p><strong>Objective: </strong>To determine whether combining eye acupuncture (EAp) with electroacupuncture (EA) produces greater analgesia in a rat KOA model via regulation of TRPV1 signaling in the spinal dorsal horn (SDH) and dorsal root ganglia (DRG).</p><p><strong>Methods: </strong>Thirty-six Sprague-Dawley rats (19 males, 17 females) were randomized into sham, model, EA, and combination (EA + EAp) groups (n = 9 per group, each containing 4-5 rats of each sex). KOA was induced by anterior cruciate ligament transection combined with medial meniscectomy. After 7 days of intervention, mechanical and thermal pain thresholds were assessed. Serum concentrations of PGE2, IL-1β, IL-6, and TNF-α were quantified by ELISA. TRPV1 expression in SDH and DRG was detected by immunofluorescence and Western blot.</p><p><strong>Results: </strong>Combination treatment significantly elevated pain thresholds and was associated with reduced levels of all four cytokines compared to the model and EA groups (P < 0.05 or P < 0.01). On day 7, the combination group showed a 2.2-fold increase in MWT compared to the model group (18.7 ± 2.6 g vs 8.5 ± 1.9 g, P < 0.001) and a 31.7% increase compared to the EA group (P < 0.01). Immunofluorescence showed the lowest TRPV1/DAPI fluorescence intensity ratio in the combination group in both DRG and SDH (P < 0.01 vs model; P < 0.05 vs EA). Western blot showed that combination therapy was associated with markedly lower total TRPV1 and phosphorylated TRPV1 (p-TRPV1) protein levels compared with the model and EA groups, with consistent trends in male and female rats.</p><p><strong>Conclusion: </strong>Combined EAp and EA exert synergistic anti-inflammatory and analgesic effects in KOA rats, which are associated with downregulation of TRPV1 signaling in the SDH and DRG.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"628497"},"PeriodicalIF":3.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Pain ResearchPub Date : 2026-10-12eCollection Date: 2026-01-01DOI: 10.2147/JPR.S632857
Shalin Feng, Jun Mou, Xiaoqin Wang, Changping Mu
{"title":"C-Reactive Protein and Risk of Low Back Pain: A Univariable and Multivariable Mendelian Randomization Study.","authors":"Shalin Feng, Jun Mou, Xiaoqin Wang, Changping Mu","doi":"10.2147/JPR.S632857","DOIUrl":"10.2147/JPR.S632857","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the causal associations of genetically predicted C-reactive protein (CRP), major depressive disorder (MDD), body mass index (BMI), and smoking initiation with low back pain (LBP) using Mendelian randomization (MR).</p><p><strong>Methods: </strong>Summary-level GWAS data for exposures and LBP (FinnGen R8) were obtained. Instrumental variables were selected at a strict genome-wide threshold (<i>P</i> < 5×10<sup>-8</sup>) and harmonized. Two-sample univariable MR was performed primarily using random-effects inverse-variance weighted (IVW). Multivariable MR (MVMR) assessed independent effects adjusting for confounders, evaluated via conditional F-statistics. Sensitivity analyses included Cochran's Q, MR-Egger, and leave-one-out diagnostics.</p><p><strong>Results: </strong>Univariable MR showed that genetically predicted circulating CRP was associated with an increased risk of LBP (IVW: <i>β</i> = 0.100, 95% CI: 0.040 to 0.160, <i>P</i> = 0.001), corroborated by the weighted median estimator. Conversely, genetically predicted MDD showed no causal association with LBP (<i>β</i> = -0.039, <i>P</i> = 0.752). In MVMR, instrument strength was robust (conditional F: CRP = 61.37, BMI = 23.30, smoking = 14.39). Elevated CRP remained an independent risk factor for LBP (<i>β</i> = 0.093, 95% CI: 0.016 to 0.170, <i>P</i> = 0.018). Additionally, smoking initiation exhibited an independent causal effect (<i>β</i> = 0.268, 95% CI: 0.081 to 0.455, <i>P</i> = 0.005), while BMI showed no direct effect (<i>β</i> = 0.129, <i>P</i> = 0.128).</p><p><strong>Conclusion: </strong>This study provides genetic evidence consistent with an independent causal association between elevated CRP levels and LBP risk, alongside smoking initiation. Genetically predicted MDD and BMI did not exhibit independent causal effects on LBP.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"632857"},"PeriodicalIF":3.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}