Pain and Therapy最新文献

{"title":"Efficacy of Neuromodulation Therapy for Neuropathy Symptom Reduction and Functional Improvement.","authors":"Stephen M Erle, Madelyn J Reilly, Andrew Lang, Alaa Abd-Elsayed","doi":"10.1007/s40122-026-00875-2","DOIUrl":"10.1007/s40122-026-00875-2","url":null,"abstract":"<p><strong>Introduction: </strong>Targeted neuromodulation therapies are increasingly used for the management of peripheral neuropathy; however, data on symptom and functional outcomes following standardized treatment courses remain limited. This report evaluates the efficacy of NeuroGen Neuromodulation treatments administered at the National Neuropathy Center, focusing on changes in sensory symptoms and functional task performance from the first treatment (T1) to the twelfth treatment (T12) over a mean treatment duration of 36 sessions.</p><p><strong>Methods: </strong>Patients completing a standardized 12-treatment course using the NeuroGen Neuromodulation device were analyzed. Outcomes included patient-reported sensory symptoms (tingling, numbness, and pain) and measures of functional task performance. Changes from baseline (T1) to posttreatment (T12) were assessed to determine treatment effectiveness, response patterns, and areas for clinical optimization.</p><p><strong>Results: </strong>Patients demonstrated clear and measurable benefits following completion of 12 treatments. The greatest improvements were observed in sensory symptoms, with tingling, numbness, and pain each improving by approximately one point on the severity scale. More than half of patients achieved clinically meaningful relief in these sensory domains. Functional improvement was more modest, with meaningful gains observed in approximately one-quarter to one-third of patients. Nonresponse rates were low, although residual symptoms and functional limitations remained common.</p><p><strong>Conclusions: </strong>The standard NeuroGen Neuromodulation treatment protocol provides substantial relief of sensory neuropathic symptoms, with consistent benefits across patients. While functional gains were less pronounced, the low nonresponse rate supports overall treatment effectiveness. Persistent symptoms in some patients suggest a potential role for maintenance therapy and adjunctive interventions to optimize long-term outcomes.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1591-1606"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-Clinic and At-Home Patient Experiences with Closed-Loop Spinal Cord Stimulation: 12-Month Outcomes from the Closed-Loop Australia Randomized Crossover Trial.","authors":"Vahid Mohabbati, Richard Sullivan, James Yu, Peter Georgius, Charles D Brooker, Malgorzata Siorek, Bonnie Ditterline, Jessica K Friedman, Marc A Russo","doi":"10.1007/s40122-026-00863-6","DOIUrl":"10.1007/s40122-026-00863-6","url":null,"abstract":"<p><strong>Introduction: </strong>Closed-loop spinal cord stimulation (CL-SCS) uses evoked compound action potential (ECAP) feedback to dynamically adjust stimulation amplitude, reducing under- and overstimulation during postural and activity changes. This manuscript reports 12-month patient-reported stimulation and pain outcomes from the Closed-Loop Australia study.</p><p><strong>Methods: </strong>This multicenter, prospective, single-arm study used randomized in-clinic crossover testing to investigate the primary outcome of overstimulation in patients using CL-SCS versus open-loop (OL) SCS during protocol-specified movements. Secondary outcomes included patient-reported stimulation characteristics for patient-informed, at-home therapy and pain intensity.</p><p><strong>Results: </strong>At 12 months, patients randomized to CL-SCS reported lower rates of overstimulation (median 0.4; IQR 0.0, 1.0) compared with OL-SCS (median 3; IQR 2.6, 4.0). Participants described the stimulation characteristics of their predominant at-home SCS therapy in terms of comfort and ability to perform activities. Eighty-five percent of participants (n = 39) reported being comfortable performing physical activity while their stimulation therapy was engaged, while 19.6% (n = 9) indicated needing to turn their therapy down or off to do certain activities. Pain intensity decreased from baseline by 60 mm and remained stable through 12 months, with 78% (n = 36) of participants achieving ≥ 50% pain relief.</p><p><strong>Conclusions: </strong>These findings suggest that adaptable stimulation strategies are important in supporting comfort and sustained pain relief.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov, NCT05177354.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1673-1684"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early MRI-Detected Interspinous Ligament Region Edema Is Associated With Delayed Pain Recovery and Persistent Low Back Pain After Unilateral Biportal Endoscopic Surgery.","authors":"Yi Mao, Jiangbao Xu, Junchao Zhang, Lei Tong, Xiangyang Wang","doi":"10.1007/s40122-026-00872-5","DOIUrl":"10.1007/s40122-026-00872-5","url":null,"abstract":"<p><strong>Introduction: </strong>Persistent postoperative low back pain remains a concern after unilateral biportal endoscopic (UBE) surgery, but the impact of surgery-related interspinous ligament edema is unclear. This study investigated whether magnetic resonance imaging (MRI)-detected interspinous ligament region edema (ISLRE) was associated with delayed pain recovery and persistent postoperative low back pain after UBE surgery.</p><p><strong>Methods: </strong>This retrospective cohort study included patients who underwent single-level UBE surgery between October 2021 and October 2024. On the basis of MRI within 3 days postoperatively, ISLRE was graded as grade 0 (no/minimal edema), grade 1 (localized edema), or grade 2 (diffuse or confluent edema involving most of the operated interspinous region). Clinical outcomes included visual analogue scale scores for low back pain (VAS-LBP), Oswestry disability index (ODI), and persistent postoperative low back pain, defined as 12-month VAS-LBP > 3. Multivariable linear and logistic regression analyses were performed to assess independent associations, and linear mixed-effects modeling was used to evaluate longitudinal pain recovery trajectories.</p><p><strong>Results: </strong>A total of 245 patients were included (grade 0: n = 117; grade 1: n = 74; grade 2: n = 54). Interobserver agreement for MRI grading was substantial (κ = 0.802). At 12 months, VAS-LBP scores increased progressively across edema grades (1.66 ± 1.20, 2.34 ± 1.45, and 3.54 ± 1.65 for grades 0-2, respectively; P < 0.001), while persistent postoperative low back pain occurred in 21.4%, 41.9%, and 68.5% of patients, respectively (P < 0.001). Compared with grade 0 edema, grade 2 edema was independently associated with higher 12-month pain scores (β = 1.78, 95% confidence interval [CI] 1.34-2.22; P < 0.001) and more than eightfold increased odds of persistent postoperative low back pain (odds ratio [OR] 8.90, 95% CI 4.01-19.76; P < 0.001). Linear mixed-effects modeling demonstrated significantly delayed pain recovery trajectories in higher-grade edema groups. Although statistically significant, the magnitude of ODI differences at 12 months was below the minimal clinically important difference (MCID) threshold, suggesting limited clinical relevance.</p><p><strong>Conclusions: </strong>The extent of postoperative ISLRE, particularly grade 2 edema, may be useful for postoperative risk stratification and targeted patient management after UBE surgery.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1553-1567"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Driving Mechanisms and Future Trends of Migraine and Tension-Type Headache Burden in G20 Countries: A Comparative Analysis Utilizing Decomposition Analysis and Explainable Machine Learning.","authors":"Zhuochen Chen, Guifen Fan, Kai Dai, Xueting Liu, Xu Cheng, Jianhong Ye, Jun Peng","doi":"10.1007/s40122-026-00859-2","DOIUrl":"10.1007/s40122-026-00859-2","url":null,"abstract":"<p><strong>Introduction: </strong>Migraine and tension-type headache (TTH) are leading causes of neurological disability globally. While their macro-trends are documented, the nonlinear drivers and the regulatory role of socio-economic development across G20 countries remain under-explored.</p><p><strong>Methods: </strong>Based on Global Burden of Disease (GBD) 2023 data, the headache burden across G20 members was quantified. Developmental trajectories were identified by integrating the Socio-demographic Index (SDI). Crucially, a comparative analysis was conducted between a decomposition analysis model and an explainable machine learning framework, Shapley Additive Explanations-Extreme Gradient Boosting (SHAP-XGBoost), to quantify nonlinear marginal contributions and complex feature interactions. Finally, future trends from 2024 to 2035 were projected utilizing Autoregressive Integrated Moving Average (ARIMA) models.</p><p><strong>Results: </strong>In 2023, the number of prevalent cases for migraine and TTH across G20 countries was estimated at 705 million and 1.27 billion, respectively. A significant nonlinear correlation between headache burden and the SDI was identified, with the burden for both disorders peaking at an SDI of approximately 0.8 before plateauing or declining. While population growth was identified as the primary macro-driver in both decomposition and SHAP analyses, a \"saturation effect\" within the headache models was revealed by SHAP analysis. Specifically, the marginal contribution of population size was found to diminish once specific thresholds were exceeded. Furthermore, according to ARIMA model projections, the age-standardized incidence rate (ASIR) of migraine is expected to stabilize in the coming years, whereas the ASIR of TTH is forecast to maintain a continuous upward trajectory through 2035.</p><p><strong>Conclusions: </strong>This study provides a comprehensive re-evaluation of migraine and TTH burden across G20 countries, shifting the focus from descriptive status quo to mechanistic explanation. Our findings confirm that while population growth remains a key contributor, variations in burden appear to be associated with differences in development level, age structure, and population scale.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1377-1400"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal Bupivacaine Incisional Infiltration for Postoperative Analgesia After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Randomized Placebo-Controlled Trial.","authors":"Haijing Zhang, Zhexuan Gong, Yan Li, Bing Li, Yang Yu, Gang Liu, Zhonghe Ji, Huan Zhang, Siyi Yan","doi":"10.1007/s40122-026-00876-1","DOIUrl":"10.1007/s40122-026-00876-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Moderate-to-severe postoperative pain is common after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence that liposomal bupivacaine provides clinically important advantages over conventional local anesthetics is inconsistent, and evidence in CRS + HIPEC remains limited. This trial evaluated the incremental efficacy and safety of liposomal bupivacaine incisional infiltration added to patient-controlled intravenous analgesia (PCIA) compared with saline infiltration plus PCIA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this single-center, randomized, participant- and assessor-blinded, placebo-controlled trial, adults aged 18-65 years scheduled for elective CRS + HIPEC were assigned 1:1 to standardized PCIA plus liposomal bupivacaine incisional infiltration (PCIA-LB) or PCIA plus normal saline infiltration (PCIA-NS). The primary endpoint was the incidence of moderate-to-severe movement-evoked incisional pain (numeric rating scale &gt;  = 4) within 72 h. The prespecified primary efficacy analysis used the per-protocol set (PPS), with a conservative intention-to-treat (ITT) sensitivity analysis. PCIA followed an institutional standard operating procedure. Monitoring was continuous in the intensive care unit (ICU); after transfer to the ward, pulse oximetry was continued through postoperative day 3, with intermittent electrocardiography and noninvasive blood pressure monitoring.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The PPS included 94 patients (PCIA-NS, n = 48; PCIA-LB, n = 46). Moderate-to-severe movement-evoked pain within 72 h was less frequent with PCIA-LB than with PCIA-NS (19.6% versus 70.8%, P &lt; 0.001). The conservative ITT sensitivity analysis supported the same conclusion (26.0% versus 68.0%, P &lt; 0.001). PCIA-LB also produced a modest reduction in cumulative 72-h study-recorded oral morphine milligram equivalents (556.8 [473.4, 600.0] versus 600.0 [557.4, 630.0] mg, P = 0.002) and reduced rescue analgesia (30.4% versus 54.2%, P = 0.020). QoR-15 scores did not differ significantly. Overall analgesia-related adverse events occurred in 23.9% and 10.4% of the PCIA-LB and PCIA-NS groups, respectively (P = 0.143). No participant required naloxone, emergency airway intervention, or ventilatory support for a clinically recognized opioid-related respiratory event, and no local anesthetic systemic toxicity, incisional infection, or fat liquefaction was observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Compared with saline infiltration, liposomal bupivacaine incisional infiltration reduced early movement-evoked incisional pain and rescue analgesia and produced a statistically significant but quantitatively modest reduction in 72-h opioid consumption captured by the study records after CRS + HIPEC. It did not improve QoR-15. These findings do not establish superiority over plain bupivacaine, ropivacaine, or catheter-based regional techniques, and the study was not powered to establish safety.&lt;/p&gt;&lt;p&gt;&lt;s","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1569-1590"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How the Reclassification of Gabapentinoids Reshaped Neuropathic Pain Treatment in Saudi Arabia: A Survey of Healthcare Professionals.","authors":"Abdullah Kaki, Yousef Hamdy, Ashraf Amir","doi":"10.1007/s40122-026-00874-3","DOIUrl":"10.1007/s40122-026-00874-3","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess knowledge gaps, perceptions, and prescribing approaches of healthcare professionals (HCPs) in Saudi Arabia regarding pain management, particularly neuropathic pain, in the context of recent reclassification of gabapentinoids.</p><p><strong>Methods: </strong>A three-lecture webinar was attended by 4922 HCPs across Saudi Arabia. Two structured surveys were embedded within the lectures: a 9-item knowledge questionnaire on pain management and a 10-item questionnaire on HCPs' opinions and attitudes on gabapentinoid use and prescribing challenges. Responses were recorded on the platform's interactive dashboard as percentage. The knowledge scores were normalized to percentage.</p><p><strong>Results: </strong>Overall knowledge levels varied across specialties with internal medicine (68.7%) and pain specialists (68.3%) having the top scores; non-pain organ specialists scored the lowest (59.1%). The majority of HCPs (68.8%) agreed that prescribing gabapentinoids has become more challenging than prescribing tramadol post reclassification, with patients' concerns related to substance dependence (32.6%) and extended process in obtaining medication (27.9%) cited by the majority. Gabapentinoids remained the preferred treatment for diabetic peripheral neuropathy by most HCPs (36.8%). Most HCPs (47.4%) reported initiating gabapentinoids at the lowest possible dose and increasing as needed, while a smaller proportion preferred initiating an appropriate dose with minimal adjustments (18.5%). Among pain specialists, these approaches were nearly evenly divided (37.7% and 31.9%, respectively). The majority (45.7%) selected pregabalin 300 mg as their preferred daily dose for transitioning from gabapentin 900 mg.</p><p><strong>Conclusions: </strong>This nationwide survey highlights substantial variability and knowledge gaps related to general pain, neuropathic pain management, and excessive caution among HCPs regarding prescribing gabapentinoids and patient concerns of developing dependence. To maintain gabapentinoid access and timely care for patients with legitimate needs, there is a need to implement educational programs for HCPs across specialties and develop a unified treatment approach that fulfils the guidelines and addresses exaggerated patient worries along with patient-focused initiatives to reduce hesitancy post reclassification of gabapentinoids.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1447-1467"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes after Onset of Mirogabalin-Related Adverse Drug Reactions in Patients with Lumbar Spinal Stenosis: Post Hoc Analysis of the MiroTAS Study.","authors":"Takuya Nikaido, Kazuhito Shiosakai, Hiroshi Sakoda","doi":"10.1007/s40122-026-00855-6","DOIUrl":"10.1007/s40122-026-00855-6","url":null,"abstract":"<p><strong>Introduction: </strong>The MiroTAS study demonstrated the pain-relieving effect and safety of mirogabalin in patients with lumbar spinal stenosis (LSS); however, whether mirogabalin-related adverse drug reactions (mrADRs) affect clinical courses, treatment continuation, or adherence remained unknown. We examined recovery outcomes and treatment status following mrADR onset and whether the analgesic effects of mirogabalin correlated with LSS and leg pain durations.</p><p><strong>Methods: </strong>This post hoc analysis of the 12-week, randomized controlled MiroTAS study summarized mrADRs (dizziness, somnolence, peripheral edema, and edema) by severity and outcome. Spearman's rank correlations between leg pain changes and duration of LSS and leg pain were examined.</p><p><strong>Results: </strong>Data from 214 patients in the modified intention-to-treat set (mirogabalin add-on: 110; nonsteroidal anti-inflammatory drugs alone: 104) and 216 in the safety analysis set (110 and 106 patients, respectively) were analyzed. Regarding mrADRs, 27/33 dizziness, 25/35 somnolence, 3/6 peripheral edema, and 2/2 edema events recovered or improved. Median times to recovery for dizziness and somnolence were 8.0 and 33.5 days, respectively. Recovery or improvement of dizziness and somnolence occurred in most patients even without dose modification, with a higher proportion of recovery following dose reduction. Most events with moderate dizziness or somnolence (80.0% and 85.7%, respectively) recovered or improved. In the mirogabalin add-on group, Spearman's rank correlation coefficients showed weak positive correlations between change in visual analogue scale (VAS) score for leg pain from baseline to week 12 and LSS duration (P = 0.0269) and no correlation between leg pain duration and change in VAS score.</p><p><strong>Conclusions: </strong>Our data suggest that dizziness and somnolence are generally manageable under careful monitoring, with most events recovered or improved after onset. The analgesic effect of mirogabalin was weakly associated with LSS duration and not associated with leg pain duration. However, this was a post hoc analysis; given the limited sample size and statistical power, further research is needed.</p><p><strong>Clinical trial registration: </strong>Japan Registry of Clinical Trials (jRCTs021200007).</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1433-1445"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Musculoskeletal Injuries with an Inflammatory Damage-Associated Molecular Pattern (DAMP) Etiology.","authors":"Ryan J Love, Jay Sheridan, Christopher Funk, Jody-Lynn Young","doi":"10.1007/s40122-026-00880-5","DOIUrl":"10.1007/s40122-026-00880-5","url":null,"abstract":"<p><strong>Introduction: </strong>Musculoskeletal injuries (MSKI) often progress from acute tissue damage to chronic pain and dysfunction when mechanical overload and microdamage sustain sterile inflammation and neuroimmune sensitization. These processes amplify nociception, impair loading tolerance, and limit the efficacy of rehabilitation, underscoring the need for mechanism-based strategies that interrupt the transition from acute injury to chronic musculoskeletal disease.</p><p><strong>Methods: </strong>This etiological review was conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. A comprehensive search of PubMed/MEDLINE and Google Scholar (1990-2026) identified mechanistic, translational, and therapeutic research reports that examined damage-associated molecular pattern (DAMP) signaling, innate immune activation, stromal cell responses, nociceptor sensitization, and interventions targeting these pathways. Eligible studies addressed DAMP-related mechanisms in musculoskeletal tissues or evaluated therapies that modulate the underlying inflammatory and mechanobiological drivers of chronic MSKI. Information was synthesized thematically to construct an integrated model of how DAMPs contribute to chronicity.</p><p><strong>Results: </strong>Across tendon, cartilage, ligament, muscle, and fibrocartilage, mechanical overload and microdamage trigger the release of DAMPs that activate Toll-like receptors (TLRs), receptor for advanced glycation end-products (RAGE), and inflammasome pathways, thereby sustaining cytokine production, stromal cell activation, and nociceptor sensitization. Persistent DAMP signaling is strongly associated with impaired inflammation resolution, failed tissue healing, and progression to chronic tendinopathy, osteoarthritis, and mechanical low back pain. Emerging therapeutic approaches, including targeted loading, regenerative injections, metabolic modulation, and immune-modifying strategies, demonstrate potential to attenuate DAMP activity, promote resolution, and restore tissue homeostasis.</p><p><strong>Conclusions: </strong>Sterile inflammation driven by DAMPs provides a unifying mechanistic framework explaining why many musculoskeletal injuries fail to resolve and instead evolve into chronic, refractory conditions. Therapies that modulate DAMP signaling, enhance inflammatory resolution, and normalize mechanobiological loading represent promising avenues for preventing or reversing chronic MSKI pathology. A mechanistically informed approach may improve clinical outcomes by addressing the etiological drivers rather than the downstream symptoms of chronic musculoskeletal disease.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1249-1279"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Short-Term Spinal Cord Stimulation for Subacute Zoster-Associated Pain: A Three-Group Propensity Score-Matched Analysis.","authors":"Wenxing Zhao, Liangliang He, Liqiang Yang","doi":"10.1007/s40122-026-00869-0","DOIUrl":"10.1007/s40122-026-00869-0","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal cord stimulation (SCS) has emerged as a promising modality for managing zoster-associated pain (ZAP). This study aimed to evaluate the efficacy and safety of short-term spinal cord stimulation (SCS) for treating ZAP during the subacute phase.</p><p><strong>Methods: </strong>Records of patients undergoing transforaminal epidural injection (TFEI), pulsed radiofrequency (PRF), and short-term SCS were retrospectively reviewed. A 1:2:2 propensity-score matching was performed. The primary endpoint was Numeric Rating Scale (NRS) pain scores at 3 months after rash onset. Secondary endpoints included postherpetic neuralgia (PHN) incidence, Hospital Anxiety and Depression (HADS) scores, Pittsburgh Sleep Quality Index (PSQI) scores, quality-adjusted life years (QALY) scores, and adverse events.</p><p><strong>Results: </strong>At 3 months post-rash onset, mean NRS pain score was 1.59 ± 1.18 in SCS cohort, which was lower than that of 4.80 ± 1.41 in TFEI cohort and 4.54 ± 1.40 in PRF cohort, with the difference exceeding the prespecified minimal clinically important difference of three points (p < 0.001). PHN occurred in 8.9% of patients in SCS cohort at 3 months and 5.9% at 6 months following rash episode, which was lower than the other two cohorts (both p < 0.001). The proportion of patients requesting weak opioids for rescue pain relief was lower in SCS cohort, with less usages, at these time points. SCS cohort had better improvements in terms of HADS, PSQI and QALY scores over time compared to both TFEI and PRF cohorts (all p < 0.05). No severe adverse events were observed.</p><p><strong>Conclusions: </strong>Among patients with subacute ZAP, short-term SCS was more effective than TFEI or PRF, resulting in greater improvements in PHN occurrence, psychological function, sleep quality, and quality of life.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1469-1482"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Non-invasive Brain Stimulation for Pain, Anxiety, and Depression: A Systematic Review and Network Meta-analysis.","authors":"Yan Li, Xiangyin Ye, Shufang Li, Jing Xu, Hongyuan Wang, Lina Pang, Yuanlin Li, Song Jin","doi":"10.1007/s40122-026-00860-9","DOIUrl":"10.1007/s40122-026-00860-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Although non-invasive brain stimulation (NIBS) has been used to manage chronic musculoskeletal pain (CMP) and related emotional symptoms, the comparative efficacy of different NIBS techniques remains unclear. Therefore, this network meta-analysis (NMA) compared the effects of NIBS interventions on pain intensity, anxiety, and depressive symptoms in CMP.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched seven databases from inception to 7 October 2025, including PubMed, the Cochrane Library, Web of Science, Embase, MEDLINE, PsycINFO, and CINAHL, and included only English-language randomized controlled trials evaluating NIBS for CMP that reported pain, anxiety, or depression outcomes. Effect sizes were synthesized using a frequentist NMA and expressed as standardized mean differences (SMDs) or mean differences (MDs) with 95% confidence intervals (CIs). Risk of bias was assessed with the Cochrane Risk of Bias 2.0 tool.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 50 randomized controlled trials were included, involving 2,203 participants with an average age ranging from 31 to 75 years; approximately 82% of the participants were women. The NMA showed that: (1) in the overall CMP population, low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (SMD = - 1.19, 95% CI - 1.86 to - 0.52), transcranial random noise stimulation (tRNS) targeting the primary motor cortex (M1) (SMD = - 1.66, 95% CI - 3.05 to - 0.28), and intermittent theta-burst stimulation (iTBS) targeting the DLPFC (SMD = - 0.78, 95% CI - 1.63 to 0.08) ranked first for pain, anxiety, and depression, respectively. Sensitivity analyses suggested that LF-rTMS targeting the DLPFC may be the most robust option for CMP with comorbid emotional symptoms; (2) in fibromyalgia, LF-rTMS targeting the DLPFC ranked first for pain (SMD = - 1.19, 95% CI - 1.99 to - 0.39) and depression (SMD = - 0.63, 95% CI - 0.98 to - 0.27), while tRNS targeting M1 (SMD = - 1.66, 95% CI - 2.99 to - 0.34) ranked first for anxiety; after excluding sparse-evidence interventions, transcranial direct current stimulation (tDCS) targeting M1 became the preferred option for anxiety; (3)in non-fibromyalgia populations, cranial electrotherapy stimulation (CES) (SMD = - 1.39, 95% CI - 2.41 to - 0.37) ranked first for pain, while iTBS targeting the DLPFC (MD = - 0.79, 95% CI - 1.48 to - 0.10) showed potential benefit for depression, although supporting evidence was limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Different non-invasive brain stimulation modalities may confer outcome-specific benefits in chronic musculoskeletal pain. Overall, low-frequency repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex showed relatively robust effects across outcomes in chronic musculoskeletal pain and on pain and depression in fibromyalgia; however, further high-quality clinical trials are needed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Prospero ","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1281-1311"},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}