Journal of Pain Research最新文献

{"title":"Efficacy of Electroacupuncture for Chronic Pelvic Pain: A Randomized, Single-Blind, Sham-Controlled Trial.","authors":"Lishi Huang, Jin Yu, Dan Gan, Yan Ding, Yeping Yang, Furui Jin","doi":"10.2147/JPR.S630526","DOIUrl":"https://doi.org/10.2147/JPR.S630526","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy and safety of electroacupuncture in the management of chronic pelvic pain (CPP).</p><p><strong>Methods: </strong>This randomized, single-blind, sham-controlled trial enrolled 66 women aged 18 to 50 years with CPP. Participants were randomly assigned in a 1:1 ratio to receive either electroacupuncture or sham electroacupuncture. Each treatment session lasted 30 minutes and was administered three times weekly, with treatment suspended during menstruation and subsequently resumed until 24 sessions were completed. The primary outcomes were lower abdominal pain and lumbosacral pain assessed using the Visual Analogue Scale (VAS) at baseline, week 8 (end of treatment), and week 16 (8-week follow-up). Secondary outcomes were depression and anxiety assessed using the Hamilton Depression Rating Scale HAMD) and Hamilton Anxiety Rating Scale (HAMA) before and after treatment.</p><p><strong>Results: </strong>Sixty-six women were randomized, with 32 assigned to electroacupuncture and 34 to sham electroacupuncture. At week 8, the reported between-group effect estimates were 3.37 (95% CI, 2.62-4.12) for lower abdominal pain and 3.14 (95% CI, 2.42-3.87) for lumbosacral pain (both <i>p</i> < 0.001). At week 16, the corresponding reported estimates were 3.69 (95% CI, 2.90-4.48) and 3.38 (95% CI, 2.63-4.13), respectively (both <i>p</i> < 0.001), indicating that the reduction in pain was maintained during follow-up. No significant between-group differences were observed in changes in HAMD or HAMA scores after treatment. No serious adverse events were reported.</p><p><strong>Conclusion: </strong>Electroacupuncture may reduce lower abdominal and lumbosacral pain in women with CPP, and the observed reduction was maintained through the 8-week follow-up period. No specific between-group benefit was demonstrated for anxiety or depressive symptoms. Larger studies with longer follow-up are warranted.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"630526"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111202","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}

{"title":"A Rat Model Mimicking Treatment-Induced Painful Diabetic Neuropathy Following Experimental Rapid Weight Loss.","authors":"Yunwei Liu, Chongsong Cui, You Peng, Yaqi Zhang, Tuoling Zhong, Hang Zhang, Qingshun Liang, Zhenjie Liu","doi":"10.2147/JPR.S641570","DOIUrl":"https://doi.org/10.2147/JPR.S641570","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the feasibility of constructing a painful diabetic neuropathy (PDN) rat model mimicking treatment-induced neuropathy (TIND) through rapid weight reduction via caloric restriction combined with metformin.</p><p><strong>Methods: </strong>Type 2 diabetes was induced using a high-fat diet combined with low-dose streptozotocin (STZ, 30 mg/kg). At week 11, rats were classified into spontaneous PDN and non-painful diabetic neuropathy (NPDN) groups based on mechanical withdrawal threshold (MWT) decline (≥50% from baseline). Rapid weight loss was subsequently induced over 10 weeks (weeks 12-21) via 40% food restriction by weight combined with metformin gavage (200 mg/kg·d). Mechanical withdrawal threshold (MWT), motor and sensory nerve conduction velocities (MNCV and SNCV), sciatic nerve histopathology, and intraepidermal nerve fiber density (IENFD) were assessed.</p><p><strong>Results: </strong>The spontaneous PDN rate at week 11 was 54.8% (17/31). Following the intervention, MWT decreased by 91.47% in the NPDN-WL group (P = 0.001) and by 91.08% in the PDN-WL group (P < 0.01). MNCV was significantly lower in both diabetic weight-loss groups than in their respective diabetic control groups. SNCV was numerically lower in the weight-loss groups, but the corresponding pairwise differences were not statistically significant after Bonferroni adjustment. Histological examination showed myelin disorganization, vacuolar degeneration, and axonal swelling, whereas IENFD showed a non-significant decreasing trend. Notably, all NPDN-WL rats (7/7) achieved complete phenotypic conversion (100%), whereas no conversion occurred in the NPDN-Con group (0/3, 0%). However, the control groups were small and unbalanced (NPDN-Con, n = 3; PDN-Con, n = 4), and these findings should be interpreted with caution.</p><p><strong>Conclusion: </strong>These preliminary findings suggest that rapid weight reduction via caloric restriction combined with metformin may offer a feasible approach for establishing a TIND-like PDN rat model, and that rapid weight loss under diabetic conditions could be an important contributing factor in the conversion toward a painful neuropathy phenotype. Further studies with larger sample sizes are warranted to substantiate these observations.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"641570"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110516","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}

{"title":"Comment on Efficacy of Acupuncture Treatment in the Treatment of Female Myofascial Pelvic Pain Syndrome: A Protocol for a Dual-Center Randomized Controlled Trial [Response to Letter].","authors":"Yangyang Ye, Weilu Dong, Liyuan Jiang","doi":"10.2147/JPR.S644750","DOIUrl":"10.2147/JPR.S644750","url":null,"abstract":"","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"644750"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111050","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}

{"title":"A Comparative Cost-Consequence Analysis of Spinal Cord Stimulation and Magnetic Peripheral Nerve Stimulation for the Treatment of Painful Diabetic Peripheral Neuropathy in an Integrated Health System.","authors":"Marshall David Bedder","doi":"10.2147/JPR.S628272","DOIUrl":"https://doi.org/10.2147/JPR.S628272","url":null,"abstract":"<p><strong>Background: </strong>Painful diabetic peripheral neuropathy (PDN) is common, progressive, and often refractory to drugs. Two neuromodulation options now carry US Food and Drug Administration indications for PDN, implanted spinal cord stimulation (SCS) and noninvasive magnetic peripheral nerve stimulation (mPNS). This study compares what the two cost an integrated health system over three years and sets those costs beside the clinical results each has published.</p><p><strong>Methods: </strong>A deterministic cost-consequence model followed 100 patients for three years at Veterans Health Administration (VHA) contract prices: $27,000 for an SCS system and $350 per mPNS session, with 17 sessions in year 1 and up to 12 a year after that. SCS revision (34%) and explant (53%) prevalences, with their median timings of 16 and 39 months, came from a published 100-patient series and were spread across the horizon. A revision was costed as lead hardware. An explant was costed as removal of the device, with nothing purchased in its place. Patients who stopped either therapy stopped generating cost. One-way, threshold, scenario, and probabilistic sensitivity analyses were run. Reporting follows CHEERS 2022.</p><p><strong>Results: </strong>Device costs over three years were $2,882,250 for SCS and $910,000 for mPNS, a difference of $1,972,250, or $19,723 per patient, and a cost ratio of 3.17. The SCS system price and the mPNS session price drove the result. Explant prevalence had no effect on device cost. mPNS cost less in every scenario tested, including a pooled systematic-review explant rate (ratio 3.17), PDN trial explant rates (3.04), no mPNS attrition (2.01), and a five-year horizon with no attrition (1.28). The two therapies reach parity only if an SCS system costs less than about $8,500 or an mPNS session costs more than about $1,110 ($700 with no attrition). mPNS was cheaper in all 10,000 probabilistic simulations (median ratio 3.21; 95% interval 2.09 to 4.82). Three-month responder rates are of similar size (79% for 10 kHz SCS against conventional management; 72% for mPNS against sham at day 30, 70% to 81% at day 90) but come from trials of different design and were not treated as equivalent.</p><p><strong>Conclusion: </strong>For a health system buying at contract prices, mPNS costs roughly a third of SCS over three years, and no plausible change in the inputs closes the gap. Head-to-head trials with quality-of-life measurement are needed before anyone can say which therapy offers better value per quality-adjusted life year. On present evidence, offering mPNS before an implanted system is a reasonable position for shared decision-making.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"628272"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109888","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}

{"title":"Strengthening Pain Resilience Through Mobile Technology: A Randomized Controlled Trial on Pain Intensity and Disability in Chronic Pain Management.","authors":"Hajar Haghshenas, Maryam Shaygan, Nilofar Pasyar, Masoume Rambod","doi":"10.2147/JPR.S637884","DOIUrl":"https://doi.org/10.2147/JPR.S637884","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is often accompanied by significant functional disability. Since people with chronic pain often experience a decrease in resilience -as a key psychological factor that significantly impacts pain intensity and disability level - the present study aimed to determine the effect of enhancing pain resilience through a smartphone-based application on pain intensity, and disability in this population.</p><p><strong>Methods: </strong>In the present randomized controlled trial, 108 patients with chronic pain were randomly assigned to three groups. Control group (A) received routine care, and control group (B) received short text-message-based educational content regarding chronic pain and its influencing factors. The intervention group patients also used the content of the enhancing resilience against chronic pain application for 8 weeks. The participants' outcomes including pain intensity and disability, were evaluated before, immediately after, and three months after the intervention. To examine the between-group differences in the mean outcome scores, ANOVA and Kruskal-Wallis tests were used. To examine the within-group differences in the mean outcome scores, repeated-measures and Friedman tests were used.</p><p><strong>Results: </strong>The study results showed a significant difference in the mean pain intensity, and disability scores between the intervention group and control groups immediately and three months after the intervention (P=0.001). The mean pain intensity score and disability score were lower in the intervention group compared to the control groups. The mean pain intensity and disability scores showed significant decreases in the intervention group from before the intervention to immediately and three months after (P=0.001).</p><p><strong>Conclusion: </strong>The results confirmed the positive effects of the smartphone-based \"Enhancing Resilience Against Chronic pain\" application on pain intensity, and disability in chronic noncancer pain patients. Given mobile phone accessibility, researchers recommend that healthcare providers, especially nurses, use virtual education to reduce pain and disability in chronic pain patients.</p><p><strong>Trial registration: </strong>Number: IRCT20210719051944N1, URL: https://www.irct.ir/trial/57624, date: 31/10/2021.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"637884"},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111122","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}

{"title":"Transcutaneous Electrical Acupoint Stimulation to Prevent Ipsilateral Shoulder Pain After Video-Assisted Thoracoscopic Surgery: A Multicenter Randomized Controlled Trial Protocol.","authors":"Shiyou Wei, Junyi Huang, Pingping Xin, Lihua Wang, Jianmang Yu, Yadan Liu, Weipeng Huang, Dandan Ling, Xin Lv","doi":"10.2147/JPR.S627058","DOIUrl":"https://doi.org/10.2147/JPR.S627058","url":null,"abstract":"<p><strong>Background: </strong>Ipsilateral shoulder pain (ISP) after video-assisted thoracoscopic (VATS) surgery is common, distinct from incisional pain, and frequently overlooked in clinical practice. Transcutaneous electrical acupoint stimulation (TEAS) is a non-invasive, safe non-pharmacological analgesic modality. This trial protocol aims to evaluate the potential preventive effect of TEAS on ISP after VATS surgery.</p><p><strong>Patients and methods: </strong>We will conduct a multicenter, single-blind randomized trial of 216 patients undergoing unilateral VATS surgery. Patients will be randomized 1:1 to receive either TEAS or sham stimulation. The TEAS group will receive two 30-minute sessions at acupoints Hegu (LI4), Neiguan (PC6), Jianliao (SJ14), and Jianyu (LI15) on the evening before surgery and before anesthesia induction on the day of surgery. The sham stimulation group will receive sensory-matched sham stimulation. The primary outcome is the incidence of ISP during shoulder movement at 24 hours postoperatively. Pain intensity will be assessed using the verbal rating scale (VRS), and ISP is defined as a VRS score ≥ 1. Secondary outcomes are cumulative opioid consumption within 24 hours postoperatively and postoperative nausea and vomiting at 24 hours. Other outcomes include shoulder pain during movement and at rest at 48 and 72 hours, opioid consumption at other time intervals, postoperative quality of recovery assessed with the 15-item Quality of Recovery scale (QoR-15), time to first flatus, and nausea and vomiting at different time points.</p><p><strong>Discussion: </strong>We hypothesize that TEAS reduces ISP incidence, opioid consumption, and improves postoperative recovery after VATS surgery. The findings of this trial will provide further evidence-based support for the prevention and management of perioperative ISP after VATS surgery, as well as a reference for the clinical application of non-pharmacological analgesic strategies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT07494591.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"627058"},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111205","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}

{"title":"Lumbar Sympathetic Radiofrequency Ablation for Peripheral Arterial Disease: A Short-Term, Self-Controlled, Retrospective Pilot Study of 16 Patients [Response To Letter].","authors":"FanZhen Lv, Yue Lin, Xinsheng Xie, Yulong Huang, Gang Chen, Shichai Hong, Xiang Hong, WeiGuo Fu, Weifeng Lu","doi":"10.2147/JPR.S658143","DOIUrl":"https://doi.org/10.2147/JPR.S658143","url":null,"abstract":"","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"658143"},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111192","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}

{"title":"Acute Pain Trajectory Phenotypes are Associated with Kinesiophobia and Functional Recovery in Surgical/Trauma ICU Patients: A 5-Year Retrospective Cohort Study Using a PERMA-Informed Framework.","authors":"Yun Li, Hao Wang, Peng Lu, Wei Jia, Yu Gao, Wei Liu, Kun Wang, Jie Ma, Xiaoqiu Liu","doi":"10.2147/JPR.S620341","DOIUrl":"https://doi.org/10.2147/JPR.S620341","url":null,"abstract":"<p><strong>Background: </strong>Early mobilization (EM) mitigates Post-Intensive Care Syndrome (PICS). However, kinesiophobia (fear of movement) driven by severe acute pain is often overlooked. This study aimed to identify acute pain trajectory phenotypes, evaluate their association with kinesiophobia, and explore outcomes under a PERMA-informed exploratory framework.</p><p><strong>Methods: </strong>A single-center retrospective cohort study was conducted including surgical/trauma ICU patients (January 2021-December 2025). Group-based trajectory modeling (GBTM) identified latent classes of pain over the first 5 ICU days. Kinesiophobia and PERMA-related proxy variables (Relationships, Accomplishment) were extracted. Multivariable logistic regression, restricted cubic splines (RCS), and Cox proportional hazards models assessed outcomes.</p><p><strong>Results: </strong>Among 586 eligible patients, four pain trajectories were identified: \"Rapid Relief\" (38.4%), \"Persistent Moderate\" (29.5%), \"Delayed Onset/Flare-up\" (21.3%), and \"Persistent Severe\" (10.8%). After adjusting for confounding factors, Delayed Onset (Adjusted OR 3.85, 95% CI 2.15-6.84) and Persistent Severe (Adjusted OR 6.12, 95% CI 3.25-11.56) trajectories were independently associated with kinesiophobia. RCS demonstrated a significant plateauing association between cumulative opioid doses and kinesiophobia. Patients with kinesiophobia exhibited significant delays in first out-of-bed mobilization, prolonged ICU lengths of stay, and a reduced likelihood of direct discharge to home. In adjusted outcome models, kinesiophobia was associated with delayed first target mobilization (HR 0.42, 95% CI 0.33-0.54, P<0.001) and lower odds of direct-to-home discharge (OR 0.21, 95% CI 0.14-0.32, P<0.001).</p><p><strong>Conclusion: </strong>Acute pain in surgical/trauma ICU patients is highly heterogeneous. Higher-risk pain trajectory phenotypes were associated with kinesiophobia, which may represent a psychological barrier to functional recovery. Prospectively testing PERMA-informed strategies-particularly family support, meaning-oriented reframing, and goal-based achievement-may help clarify whether this approach can disrupt the pain-fear-immobility cycle.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"620341"},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110604","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}

{"title":"Cognitive Behavioral Therapy and Pain Chronification: Neuroimmune Rationale, Evidence Boundaries, and Trial Design Priorities: A Structured Narrative Review.","authors":"Yi Xi, Tianqi Zhang, Xingwei Zhao, Xia Xiong, Cehua Ou","doi":"10.2147/JPR.S635577","DOIUrl":"https://doi.org/10.2147/JPR.S635577","url":null,"abstract":"<p><strong>Background: </strong>Pain chronification is a dynamic transition in which persistent pain may be shaped by interacting nociceptive, peripheral, spinal, supraspinal, neuroimmune, endocrine and cognitive-affective processes. Cognitive Behavioral Therapy (CBT) has clinical value in chronic pain, but claims about glial modulation and disease modification require careful qualification.</p><p><strong>Objective: </strong>To evaluate CBT as an early, mechanism-informed and hypothesis-generating intervention while distinguishing clinical efficacy, neuroimmune plausibility, prevention hypotheses and disease-modifying claims.</p><p><strong>Methods: </strong>We conducted a structured narrative review using prespecified evidence domains. PubMed/MEDLINE searches covering January 2014 to September 10, 2026 were complemented by citation chasing and selected landmark mechanistic articles. Sources were organized by evidence domain, study type and interpretive role, including pain chronification, neuroimmune and glial mechanisms, brain-network mechanisms, CBT outcomes, psychoneuroimmune pathways, perioperative prevention hypotheses, risk phenotyping and scalable delivery. No quantitative pooling or formal systematic/scoping-review workflow was performed.</p><p><strong>Results: </strong>Experimental and translational studies support neuroimmune contributions to central sensitization and pain maintenance, whereas human evidence for direct CBT effects on microglial or astrocytic activation remains insufficient. CBT produces reproducible, generally small effects on pain intensity and more consistent benefits for interference, disability, distress, coping, sleep and function.</p><p><strong>Conclusion: </strong>CBT should be presented as a clinically valuable component of multimodal care and as a testable psychoneuroimmune hypothesis, not as a proven preventive, glial-targeting or disease-modifying treatment. Risk-stratified, early, component-specific and mechanism-embedded trials are needed before prevention claims are made.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"635577"},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111083","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}

{"title":"Rethinking the Boundaries of Local Anesthetic Systemic Toxicity in the Era of Sustained-Release Formulations.","authors":"Ming Liu, Xiangyang Guo, Zhengqian Li","doi":"10.2147/JPR.S644528","DOIUrl":"https://doi.org/10.2147/JPR.S644528","url":null,"abstract":"<p><p>Sustained-release local anesthetic formulations introduce prolonged and dynamic exposure patterns that challenge current frameworks for assessing local anesthetic systemic toxicity (LAST). Recent pharmacovigilance findings, pharmacokinetic evidence, and reports of delayed and recurrent LAST further support the need to re-evaluate LAST across three conceptual boundaries. First, the exposure boundary challenges the use of recommended maximum doses as stand-alone safety thresholds. Co-administration, formulation stability, and the local tissue microenvironment may influence drug release and systemic exposure. Second, the temporal boundary emphasizes that a lower initial peak plasma concentration does not necessarily imply a shorter window of vulnerability, particularly when systemic exposure is prolonged or follows a bimodal pattern. Third, the resuscitation endpoint boundary highlights that return of spontaneous circulation (ROSC) does not necessarily indicate resolution of the underlying toxicological process, as hemodynamic instability may recur after initial ROSC. Assessment of LAST associated with sustained-release formulations should not be limited to administered dose or peak plasma concentration but should consider the entire exposure trajectory. Future guidelines should also define long-term monitoring windows, specific triggers for continuous infusion of lipid emulsion, and safe upper limits for lipid emulsion dosing.</p>","PeriodicalId":16661,"journal":{"name":"Journal of Pain Research","volume":"19 ","pages":"644528"},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111135","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}