Molecular Pain最新文献

{"title":"Resveratrol alleviates neuropathic pain after spinal cord injury by suppressing δ-catenin palmitoylation-mediated membrane accumulation of Nav1.6 in the spinal dorsal horn.","authors":"Ling-Jun Xu, Qian Yang, Yu-Dan Li, Yi-Dan Zou, Yi-Ting Zhu, Xing-Hui He, Wei Wu, Li Chen, Cui-Cui Liu","doi":"10.1177/17448069261479191","DOIUrl":"10.1177/17448069261479191","url":null,"abstract":"<p><p>Neuropathic pain is a severe adverse complication of spinal cord injury (SCI) for which effective therapies are currently lacking. Resveratrol, a natural phytoalexin found in many plants and fruits, has been shown to relieve chemotherapy- and nerve injury-induced neuropathic pain and to promote functional recovery after SCI. In this study, we found that intraperitoneal administration of resveratrol increased the expression and activity of silent information regulator 1 (SIRT1) in the rat spinal dorsal horn and markedly attenuated neuropathic pain after SCI while improving motor recovery. Building on our previous finding that palmitoylation of δ-catenin promotes the membrane trafficking of the voltage-gated sodium channel Nav1.6 in dorsal root ganglion neurons and contributes to oxaliplatin- and nerve injury-induced neuropathic pain, we further examined whether resveratrol produces analgesia by inhibiting δ-catenin palmitoylation-mediated membrane accumulation of Nav1.6 in the spinal dorsal horn after SCI. Our results showed that SCI markedly increased both Nav1.6 membrane localization and δ-catenin palmitoylation in the dorsal horn and intrathecal delivery of Nav1.6 shRNA or pharmacological inhibition of palmitoylation with 2-bromopalmitate significantly attenuated mechanical allodynia after SCI. Resveratrol suppressed SCI-induced δ-catenin palmitoylation and reduced the pathological membrane accumulation of Nav1.6, an effect accompanied by downregulation of the palmitoyl acyltransferase ZDHHC3 (DHHC3). Together, these findings indicate that resveratrol alleviates neuropathic pain after SCI by inhibiting DHHC3-mediated δ-catenin palmitoylation and thereby suppressing the membrane trafficking of Nav1.6 in the spinal dorsal horn.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261479191"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721331","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":"Serum miR-145-5p as a predictive biomarker for postoperative pain after percutaneous kyphoplasty.","authors":"Min Fang, Juan Wang, Yongliang Zhu, Hui Zhao","doi":"10.1177/17448069261456426","DOIUrl":"10.1177/17448069261456426","url":null,"abstract":"<p><strong>Background: </strong>Thoracolumbar compression fractures are common in older adults. Percutaneous kyphoplasty (PKP) is a standard minimally invasive treatment, but 30%-50% of patients still have persistent or inadequate pain relief after the procedure.</p><p><strong>Objective: </strong>To investigate the predictive value and mechanism of serum microRNA-145-5p (miR-145-5p) in PKP-related postoperative pain and to support precise pain assessment and intervention.</p><p><strong>Method: </strong>Ninety-five patients with thoracolumbar compression fractures treated with PKP were divided into a low pain group (49 cases, VAS 0-3) and a high pain group (46 cases, VAS 4-10) based on 1-month postoperative VAS scores. Fasting venous blood was collected preoperatively and 1 month postoperatively. Serum miR-145-5p and erythroblastic oncogene B4 (ErbB4) levels were measured by qPCR. An LPS-induced inflammatory model was established in RSC96 cells, and their target relationship and effects on inflammation were assessed via cell transfection, enzyme-linked immunosorbent assay (ELISA), and a dual-luciferase reporter gene assay. Logistic regression identified influencing factors, and ROC analysis evaluated the predictive value of miR-145-5p.</p><p><strong>Results: </strong>The high pain group had higher preoperative VAS scores, lower bone density <i>T</i>-scores, lower miR-145-5p levels and higher ErbB4 levels. miR-145-5p targets the 3'UTR of ErbB4, inhibiting inflammation by regulating ErbB4. Preoperative VAS score, bone density <i>T</i>-score, and miR-145-5p level were independent predictors of moderate-to-severe postoperative pain. Preoperative miR-145-5p had predictive value.</p><p><strong>Conclusion: </strong>Preoperative serum miR-145-5p is a potential biomarker for assessing PKP-related postoperative pain, aiding precise intervention.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261456426"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988336","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":"Bradykinin B2 receptor triggers ITPR1-Mediated ER calcium release in trigeminal ganglion neurons to drive trigeminal neuropathic pain.","authors":"Hao-Bo Zhao, Chun-Yu Dong, Meng-Lu Liu, Jun-You Wu, Yue-Juan Ling, Bing Zhu, Lin-Peng Zhu, Yong-Jing Gao, Huan-Jun Lu","doi":"10.1177/17448069261468209","DOIUrl":"10.1177/17448069261468209","url":null,"abstract":"<p><p>ObjectiveTo elucidate the role and underlying mechanism of bradykinin (BK) B2 receptor and its downstream inositol 1,4,5-trisphosphate receptor type 1 (ITPR1)-mediated endoplasmic reticulum (ER) calcium release signaling in the development and maintenance of trigeminal neuropathic pain.MethodsA partial infraorbital nerve transection (pIONT) mouse model of trigeminal neuralgia was employed. Mechanical allodynia was assessed using von Frey filaments. The expression and localization of BK, B2 receptor, and related molecules in the trigeminal ganglion (TG) were analyzed by quantitative real-time PCR (qPCR), Western blot, and immunofluorescence staining. Whole-cell patch-clamp recordings were performed to evaluate TG neuronal excitability. Intracellular calcium signals induced by BK were monitored through Fluo-4 AM calcium imaging. Pharmacological and genetic interventions were conducted via local TG injection of B2 receptor antagonist Icatibant, ITPR1 inhibitor 2-APB, and <i>Itpr1</i>-siRNA.ResultspIONT induced persistent facial mechanical allodynia in mice, accompanied by a significant upregulation of BK mRNA and B2 receptor expression in the TG, which was primarily localized to myelinated neurons (NF200+), peptidergic neurons (CGRP+), and non-peptidergic neurons (IB4+). Local injection of Icatibant into the TG significantly alleviated mechanical nociceptive responses and reduced the hyperexcitability of nociceptive neurons. Calcium imaging showed that BK evoked ITPR1-dependent ER calcium release in TG neurons, which was abolished by both 2-APB and <i>Itpr1</i>-siRNA. Co-application of 2-APB also reversed BK-induced neuronal hyperexcitability and attenuated facial withdrawal responses.ConclusionFollowing peripheral nerve injury, the B2 receptor-ITPR1 signaling mediated ER calcium release represents an essential mechanism underlying the development and maintenance of trigeminal neuropathic pain. Targeting this signaling pathway effectively attenuates peripheral neuronal hyperexcitability, providing novel experimental evidence and potential therapeutic targets for the management of trigeminal neuralgia.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261468209"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448059","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":"Arrow promotes nociceptive sensitivity in <i>Drosophila melanogaster</i>.","authors":"Trevor Flanagan, Michael Caterina, Tatiana Muteba, Julie Moulton, Geoffrey Ganter","doi":"10.1177/17448069261453747","DOIUrl":"10.1177/17448069261453747","url":null,"abstract":"<p><p>Normal sensitivity of the <i>Drosophila</i> larval nociceptor requires the activity of the Wg/WNT signaling pathway. When the nociceptor expression of Wg/WNT co-receptor Arrow, <i>Drosophila</i> ortholog of LRP5/6, is impaired by RNA interference, the larva becomes significantly hyposensitive to noxious thermal and mechanical stimulation. The reduced sensitivity was not associated with significant changes in dendritic architecture.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261453747"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942183","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":"Impact of estrous cycle, gonadectomy (ovariectomy or castration), and selective G-protein estrogen receptor agonism on inflammatory pain in wild-type mice.","authors":"Robert C Barnes, America Alanis, Hannah Quick, Josée Guindon","doi":"10.1177/17448069261421801","DOIUrl":"10.1177/17448069261421801","url":null,"abstract":"<p><p>Inflammatory pain is a key component of acute traumatic pain and chronic rheumatic disease, which significantly reduces the quality of life of those who suffer from it and is often refractory to treatment. One contributor to the failure of current treatments is that the majority of pain testing has historically been performed in male subjects while the majority of pain patients are women. To better manage inflammatory pain, first the baseline sex differences in its experience must be assessed. Therefore, we evaluated C57BL/6J male and female mice for baseline sex differences in the formalin model of inflammatory pain, further investigating the observed significant sex differences through both assessing female mice at each phase of the estrous cycle and through examining the effects of gonadectomy (ovariectomy or castration) within the formalin model of inflammatory pain. Female mice in the metestrus or diestrus phase had decreased inflammatory pain relative to both male mice and female mice in the proestrus or estrus phase. Ovariectomy resulted in decreased pain, which was restored through treatment with estradiol (E2). Castration similarly reduced pain in male mice. Injection of the G-protein coupled estrogen receptor (GPER) agonist G1 resulted in significant antinociception in both female and male mice, in both mice that had received sham surgery or gonadectomy. These results establish baseline sex differences in the formalin model of inflammatory pain and support the need for further investigation into the interaction between estrogen, its receptors, and testosterone in the regulation of nociception.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261421801"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053243","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":"CXCL12/CXCR4 axis in neuropathic pain: Insights from preclinical models and translational implications.","authors":"Ming Li, Xiao-Xiao Lu, Lu-Yao Cai, Tao Zhu, Jin Cui","doi":"10.1177/17448069261444493","DOIUrl":"10.1177/17448069261444493","url":null,"abstract":"<p><p>Neuropathic pain affects approximately 7%-10% of the global population, significantly impairing patients' quality of life and placing a substantial burden on public health systems. Current pharmacological treatments have limited efficacy and are often accompanied by notable side effects, highlighting the urgent need for novel therapeutic targets. Increasing evidence supports the important role of chemokines and their receptors in neuro-immune interactions underlying pain sensitization. Among these pathways, the CXCL12/CXCR4 axis has emerged as an important regulator of both the initiation and maintenance of neuropathic pain. Beyond its canonical function in immune cell trafficking, the CXCL12/CXCR4 axis modulates neuronal excitability, glial activation, synaptic plasticity, and nociceptive sensitization. Notably, this axis is frequently upregulated in both peripheral and central neurons, as well as in multiple glial populations, including astrocytes, microglia, and satellite glial cells, across diverse neuropathic pain models. Importantly, CXCR4 is one of the few chemokine receptors with a clinically approved antagonist, highlighting its unique translational potential. This review systematically summarizes the expression patterns, biological functions, and pain-related mechanisms of the CXCL12/CXCR4 axis in preclinical models of neuropathic pain and discusses current limitations and potential future therapeutic strategies targeting this pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261444493"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639418","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":"Contralateral electroacupuncture modulates the transmission of nociceptive information in the spinal dorsal horn via GABAergic neurons in the rostral ventromedial medulla.","authors":"Kailing Zhang, Qingquan Yu, Yang Yang, He Zhu, Lingling Yu, Zhiyun Zhang, Kexing Wan, Jiajia Huang, Ping Peng, Jiwei Yao, Xianghong Jing, Man Li","doi":"10.1177/17448069261421426","DOIUrl":"10.1177/17448069261421426","url":null,"abstract":"<p><p>Recent studies have shown that electroacupuncture (EA) can exert analgesic effects by modulating wide dynamic range (WDR) neurons in the spinal dorsal horn; however, how EA regulates WDR neurons to inhibit pain signals remains unclear. In this study, we identified a key brain region, rostral ventromedial medulla (RVM), involved in the modulation of spinal WDR neurons. Subsequently, we found evidence suggesting that GABAergic neurons in the RVM may mediate the transmission of nociceptive and non-nociceptive signals from the spinal cord, which underlies EA analgesia. The results demonstrated that the activation of RVM GABAergic neurons enhanced the excitability of WDR neurons, thereby facilitating the transmission of peripheral sensory signals within the spinal cord. Contralateral EA at 2 mA effectively suppressed WDR neuron activity and elevated pain thresholds in rats modeled with complete Freund's adjuvant (CFA). Notably, heightened activity of RVM GABAergic neurons mitigated the inhibitory effects of EA on WDR neurons and reduced EA-induced analgesia. These findings suggest that EA may attenuate WDR neuronal activity by modulating RVM GABAergic neurons, thereby inhibiting nociceptive transmission. This study highlights the potential involvement of RVM GABAergic neurons and identifies the efficacy of high-intensity, contralateral EA stimulation in producing analgesia.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261421426"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276477","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":"Circulating cellular senescence biomarkers in persons with chronic knee osteoarthritis pain: An exploratory study.","authors":"Muhammad Abbas, Javier A Tamargo, Carlos J Cruz, Yutao Zhang, Stephanie Wohlgemuth, Kevin Wu, Li Chen, Roland Staud, Roger B Fillingim, Christiaan Leeuwenburgh, Yenisel Cruz-Almeida","doi":"10.1177/17448069261422994","DOIUrl":"10.1177/17448069261422994","url":null,"abstract":"<p><p>The senescence-associated secretory phenotype (SASP) contributes to tissue degeneration and inflammation, yet its role in osteoarthritis (OA)-related pain remains poorly understood. We hypothesized that circulating SASP markers would be associated with distinct OA-pain phenotypes, defined by pain impact and radiographic OA (ROA) severity. A subset of middle-to-older-aged adults (45-85 years) from a larger multi-site study (<i>n</i> = 169) self-reported pain impact - defined as the extent to which pain interferes with daily functioning - and underwent knee radiography and blood collection. Hierarchical cluster analysis was used to empirically identify OA-pain phenotypes based on combined pain impact and Kellgren-Lawrence (KL) grade. Plasma levels of four SASP markers (GDF-15, activin-A, Osteopontin (OPN), and IL-15) were quantified from whole blood samples. Among 169 participants, 35.5% reported high-impact chronic knee pain and 27.8% exhibited moderate-to-severe radiographic OA. Cluster analysis identified distinct ROA-pain phenotypes. GDF-15 levels were significantly elevated in non-Hispanic White females with early ROA and high-impact pain, with race- and sex-dependent differences. Activin-A levels were higher in non-Hispanic Black participants without pain or ROA and varied by sex in early ROA/low-impact pain phenotypes. Osteopontin levels were elevated in males compared to females within the same phenotype group. IL-15 levels showed no association with ROA-pain phenotypes but were higher in males and positively correlated with age. SASP factors, particularly GDF-15, Activin-A, and Osteopontin, demonstrated race- and sex-dependent associations with OA-pain phenotypes. These findings underscore the importance of demographic context in OA pathophysiology and support further investigation into SASP factors as potential biomarkers and therapeutic targets for OA-related pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261422994"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100512","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":"Beyond restless sleep: A cross-sectional study of obstructive sleep apnea risk, aging biomarkers, and chronic low back pain.","authors":"Khalid W Freij, Fiona Bat Agbor, Philemon Domoyeri, Kiari R Kinnie, Asia M Wiggins, Demario S Overstreet, Tammie L Quinn, Shivraj S Grewal, S Justin Thomas, Walid W Freij, Shameka L Cody, Michael A Owens, Robert E Sorge, Burel R Goodin, Edwin N Aroke","doi":"10.1177/17448069261427979","DOIUrl":"10.1177/17448069261427979","url":null,"abstract":"<p><p>This secondary data analysis aimed to determine the nature of the relationship between obstructive sleep apnea (OSA) risk, biological age acceleration, and nonspecific chronic low back pain (CLBP). In total, 199 adults aged 18-82 years who filled both STOPBANG and pain questionnaires subsetted for secondary analysis. Based on the STOPBANG questionnaire, 104 had a low OSA risk and 95 had an intermediate or high OSA risk. Dunedin Pace of Aging Computed from the Epigenome (DunedinPACE), Horvath's, Hannum's, PhenoAge, and GrimAge clocks were used to determine biological age and pace of biological aging. Individuals with low OSA risk reported increased DunedinPACE compared to those with intermediate/high OSA risk (<i>p</i> < 0.001). There was a significant correlation between the risk for OSA and biological age acceleration measured by PhenoAge as well as pace of biological aging (<i>p</i> < 0.05). Mediation analysis detected indirect effects of OSA risk on chronic pain outcomes through the pace of biological aging. Targeted interventions addressing OSA risk offers a promising therapeutic strategy. This could be particularly valuable for aging populations where both accelerated biological aging and chronic pain conditions are prevalent, offering a more holistic approach to improving nonspecific chronic pain outcomes through quality of sleep and restfulness.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261427979"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213443","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":"Endoplasmic reticulum stress contributes to high-dose radiation-induced chronic mechanical and thermal neuropathic pain.","authors":"Liya Dai, Wenwen Gao, Yanjie Wang, Aijuan Sun, Jie Pan, Sijia Huang, Yingtian Zhang, Yaping Cheng, Jialong Tao, Hui Wang, Zhengyang Feng, Cunjin Su, Yusong Zhang","doi":"10.1177/17448069261479181","DOIUrl":"10.1177/17448069261479181","url":null,"abstract":"<p><p>IntroductionExposure to high doses of radiation can cause serious harm to human health and lead to long-term chronic pain. However, the mechanisms underlying pain caused by radiation overexposure remain largely unknown.MethodsIn this study, the double hind paws and tail of mice were exposed to 40Gy electron beams to establish a radiation-induced pain model.ResultsEven after the inflammation of the irradiated skin subsided, the mice continued to exhibit prolonged mechanical and thermal pain. The results indicated that the neuron injury marker activating transcription factor 3 (ATF3) was markedly increased and neuronal excitability was significantly increased 1 month post-radiation in the lumbar dorsal root ganglion (DRG). Yet, radiation-induced chronic pain could not be mitigated by common analgesics. We discovered that endoplasmic reticulum (ER) stress was activated in the DRG, and intraperitoneal injections of the ER stress antagonists 4-phenylbutyric acid (4-PBA) and TUDCA significantly alleviated mechanical and thermal allodynia. Additionally, 4-PBA and TUDCA reduced the neuronal hyperexcitability caused by radiation. Moreover, 4-PBA also ameliorated the motor dysfunction induced by high-dose radiation.InterpretationOur findings highlight the pivotal role of ER stress activation in the development of chronic neuropathic pain induced by high doses of radiation. Furthermore, our findings suggest that targeting ER stress may offer a promising approach for preventing chronic abnormal pain resulting from high doses of radiation.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261479181"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726660","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}