Neurobiology of Pain最新文献

{"title":"Early NGF–TrkA–CGRP signaling-related changes in dorsal root ganglia are associated with mechanical hypersensitivity in a zymosan A-induced SKG model prior to overt arthritis","authors":"Yumi Kawata,&nbsp;Hiroshi Funakoshi","doi":"10.1016/j.ynpai.2026.100222","DOIUrl":"10.1016/j.ynpai.2026.100222","url":null,"abstract":"<div><div>Pain in axial spondyloarthritis (axSpA) may precede clinically detectable inflammation or persist despite adequate control of inflammation. However, the mechanisms underlying this early pain state remain incompletely understood. We investigated nerve growth factor (NGF)–TrkA–calcitonin gene-related peptide (CGRP) signaling in dorsal root ganglia (DRG) before the onset of overt clinical arthritis, using a zymosan A (ZyA)-induced SKG mouse model of inflammatory arthritis with SpA-like features. Female SKG mice received ZyA, with or without a prophylactic anti-NGF monoclonal antibody treatment. Mechanical sensitivity, NGF protein levels in skin tissue, and expression of CGRP, TrkA and phosphorylated TrkA in DRG neurons were evaluated on day 10. ZyA-treated mice developed mechanical hypersensitivity by day 10, while no increase in clinical arthritis scores was observed during this period.</div><div>In DRG neurons, an altered size distribution of CGRP-positive neurons toward larger-diameter populations was observed in association with early pain-related behavioral changes. These changes may involve downstream TrkA signaling. Prophylactic anti-NGF treatment attenuated the decrease in mechanical thresholds and reduced CGRP-neuronal size distribution changes and TrkA signaling changes. These findings suggest that NGF-associated DRG sensitization contributes to early pain-related behavioral changes during a prodromal phase of ZyA-induced disease, before overt clinical arthritis is established. Our study supports a mechanistic link between early pain-related behavioral changes and NGF-associated DRG sensitization, providing a rationale for further investigation of NGF-targeted strategies for pain management in axSpA.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100222"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the expression of calcitonin gene-related peptide (CGRP) and its receptor: a review of contradictory and nuanced findings","authors":"Dinobi Offurum,&nbsp;Rebecca Lorsung,&nbsp;Radi Masri,&nbsp;Asaf Keller","doi":"10.1016/j.ynpai.2026.100230","DOIUrl":"10.1016/j.ynpai.2026.100230","url":null,"abstract":"<div><div>Women are disproportionately affected by chronic pain, exhibiting greater incidence, severity, and duration of pain across a wide range of conditions. Women with chronic pain are also more likely to develop comorbid affective disorders, such as depression and anxiety. Although societal and environmental factors contribute to this sex bias, biological factors are also thought to play a role in these sex differences. One biological factor is calcitonin gene-related peptide (CGRP), a neuropeptide with established roles in the pathogenesis of several chronic pain conditions, including migraine. A prevailing hypothesis is that differences in the expression of CGRP and its receptor are involved in sex differences in chronic pain. We explore the evidence for this by reviewing the literature. We find that only a few studies, typically with small sample sizes, address this hypothesis. In aggregate, these studies provide nuanced and contradictory evidence for sex differences in the expression of CGRP and its receptor. However, we present published data that support the conclusion that the CGRP pathway functions differently in males and females.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100230"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148843462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring structural connectivity alterations in CRPS: Insights from diffusion imaging and clinical correlates","authors":"Martin Domin,&nbsp;Sebastian Strauss,&nbsp;Martin Lotze","doi":"10.1016/j.ynpai.2026.100234","DOIUrl":"10.1016/j.ynpai.2026.100234","url":null,"abstract":"<div><div>In recent years, functional and structural brain imaging studies have accumulated heterogeneous evidence for brain-wide changes accompanying complex regional pain syndrome (CRPS). We tested possible white matter pathologies in patients with CRPS in the chronic stage in comparison to matched healthy controls. We investigated possible alterations of structural connectivity using multi-directional diffusion-weighted imaging (MDDW) in a sample of 25 patients with unilateral upper limb CRPS and 19 matched controls. In a global approach we performed tract-based spatial statistics (TBSS) to evaluate possible structural differences between groups and/or association with clinical parameters (disease duration, pain intensity, CRPS severity score/CSS, somatosensory and motor function) for the patient group. In a hypothesis-driven approach (hypotheses were predefined in a trial), we tested differences between groups for fractional anisotropy (FA) in specific tracts (thalamus-M1/S1; accumbens-thalamus; anterior insula- PFC; corpus callosum between primary hand motor representations) and associations of FA and clinical parameters. We found no significant differences between patients and HCs for both approaches. However, when calculating associations between corpus callosal tract quantification and clinical parameters we detected decreased fractional anisotropy in association with disease persistence: the longer CRPS symptoms persisted, the lower callosal white matter quantification values between both M1 upper limb representations. Further studies have to address altered interhemispheric interaction with clinical features and the possible impact for new treatment strategies.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100234"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The central neurometabolic fingerprint of persistent spinal pain syndrome type 2: A prospective [18F]FDG PET/CT neuroimaging study","authors":"Lara S. Burmeister,&nbsp;Max van Grinsven,&nbsp;Bert-Kristian van Roosendaal,&nbsp;Richard L. Witkam,&nbsp;Inge Arnts,&nbsp;Stephanie Janssen,&nbsp;Jessica Wegener,&nbsp;Kris C.P. Vissers,&nbsp;Anne I.J. Arens,&nbsp;Martin Gotthardt,&nbsp;Michael Rullmann,&nbsp;Dylan Henssen","doi":"10.1016/j.ynpai.2026.100235","DOIUrl":"10.1016/j.ynpai.2026.100235","url":null,"abstract":"<div><div>Persistent spinal pain syndrome type 2 (PSPS-T2) is a disabling pain condition that persists after spinal surgery. While spinal cord stimulation (SCS) offers symptomatic relief, objective biomarkers to guide diagnosis and treatment are lacking.</div><div>In this prospective cohort study, fifteen PSPS-T2 patients underwent dedicated [¹⁸F]FDG PET/CT brain imaging prior to SCS implantation. Group-level metabolic patterns were compared to matched healthy controls using statistical parametric mapping. Regional metabolism was correlated with pain scores and neurotransmitter PET atlases using JuSpace.</div><div>PSPS-T2 patients exhibited a distributed pattern of altered glucose metabolism involving frontal, temporal and cerebellar regions. Significant hypermetabolism was observed in the left temporal pole, right inferior temporal gyrus, and bilateral cerebellar lobule VIII, whereas hypometabolism was identified in the right fusiform gyrus, right superior frontal gyrus, left gyrus rectus, and cerebellar vermis. Moreover, there were significant spatial correlations between these metabolic changes and serotonergic and glutamatergic neurotransmitter systems. Furthermore, higher baseline pain was associated with increased frontal and temporal metabolism, whereas post-intervention pain was negatively correlated with metabolism in the temporal pole.</div><div>These findings suggests that PSPS-T2 is characterized by network-level alterations in brain regions integrating sensory, emotional, and cognitive aspects of pain, with a neurochemical signature implicating serotonergic and glutamatergic systems. Although preliminary, this works provides evidence for a disease-relevant neurometabolic profile and highlights the potential of [¹⁸F]FDG PET/CT for investigating central pain mechanisms. Future research should focus on validating this marker in larger populations.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100235"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149211195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetrathiomolybdate reduces bone cancer pain and tumor-associated osteoclast activation through copper-dependent LOX signaling.","authors":"Haonan Yu,&nbsp;Xinru Yuan,&nbsp;Xin Li,&nbsp;Jiayu Tong,&nbsp;Chengya Huang,&nbsp;Xingji You,&nbsp;Jingxiang Wu","doi":"10.1016/j.ynpai.2026.100226","DOIUrl":"10.1016/j.ynpai.2026.100226","url":null,"abstract":"<div><div>Bone cancer pain (BCP) affects most patients with bone metastases and is poorly managed by current analgesics. This study evaluated tetrathiomolybdate (TTM), a clinical copper chelator, for its potential to simultaneously target osteoclast activation and copper-dependent tumor growth in BCP. Using a mouse model with intrafemoral Lewis lung carcinoma cells, TTM (20–40 mg·kg⁻¹ daily) significantly reduced mechanical allodynia and thermal hyperalgesia, even when treatment began after pain establishment. TTM suppressed osteoclast differentiation markers in bone tissue and bone marrow-derived macrophages cultures. It also directly inhibited tumor cell viability <em>in vitro</em> and reduced tumor burden <em>in vivo</em> by 43%. Mechanistically, TTM downregulated lysyl oxidase (LOX) in tumor bone, and exogenous LOX partially reversed the inhibitory effect of TTM on osteoclasts differentiation. These findings suggest that TTM alleviates BCP potentially through inhibition of copper-dependent tumor progression and attenuation of LOX-associated osteoclast activation. Our results support further investigation of copper-dependent signaling pathways as potential modulators of tumor-associated bone destruction and cancer-induced pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100226"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148587562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter differences in motor and affective-motivational networks of pain-indifferent carriers of the R221W mutation","authors":"Arnas Tamasauskas ,&nbsp;Irene Perini ,&nbsp;Jan Minde ,&nbsp;Simon S. Keller ,&nbsp;Nicholas Fallon ,&nbsp;Bernhard Frank ,&nbsp;India Morrison ,&nbsp;Andrew Marshall","doi":"10.1016/j.ynpai.2026.100211","DOIUrl":"10.1016/j.ynpai.2026.100211","url":null,"abstract":"<div><div>The R221W mutation on the nerve growth factor gene results in reduced peripheral C-nociceptor density and behavioural indifference to painful stimuli. While functional neuroimaging has revealed altered cortical and sub-cortical pain processing in R221W carriers, structural white matter changes remain unexplored and may suggest an anatomical basis of symptoms. Heterozygous R221W carriers’ (n = 11) and matched controls’ (n = 11) diffusion MRI data were compared using fixel-based analysis, and complimentary edge and node analyses using graph theory and network-based statistics. Whole-brain and region of interest (ROI) fixel-based analyses revealed significantly reduced fibre density and fibre-bundle cross-section in brainstem motor tracts of R221W carriers, encompassing the corticospinal pathways, corona radiata, external capsule, cerebellar peduncles, and pontine crossing (p &lt; 0.05). Graph theory analysis of pain-processing ROIs demonstrated significantly reduced node degree and betweenness centrality in the Left Anterior Cingulate Cortex (ACC) of R221W carriers, indicating structural isolation of this affective-motivational hub. Network-based statistics identified significantly stronger connectivity between the Right Thalamus and Right ACC in R221W carriers, in contrast to weaker connectivity connecting the Right Thalamus to the Left ACC and Left Insula (p &lt; 0.05). These findings indicate potentially reduced brainstem motor tract integrity and altered cortical network topology, specifically the structural isolation of the Left ACC. This, alongside potentially compensatory right-sided thalamo-cortical connectivity and preserved sensory afferent pathways, supports a model of R221W pain indifference as motor under-reactivity rather than sensory insensitivity.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Cortico-Thalamic reorganization in Opioid-Induced hyperalgesia and neuropathic pain male rats","authors":"Aoling Cai ,&nbsp;Qing Liu ,&nbsp;Wenchang Zhou ,&nbsp;Danhao Zheng ,&nbsp;Wen Zhang ,&nbsp;Xiaodong Liu ,&nbsp;Mamatmusayeva Nilufar ,&nbsp;Anne Manyande ,&nbsp;Feng Gao ,&nbsp;Jie Wang ,&nbsp;Jun Fang ,&nbsp;Xuebi Tian","doi":"10.1016/j.ynpai.2025.100206","DOIUrl":"10.1016/j.ynpai.2025.100206","url":null,"abstract":"<div><div>Both opioid use and peripheral nerve injury can lead to hyperalgesia. Whereas in peripheral nerve injury, the central neuroplastic is secondary to sustained peripheral signaling, opioid-induced hyperalgesia (OIH) involves maladaptive alterations in both the peripheral and central nervous systems. However, the precise neurobiological mechanisms underlying these two distinct forms of hyperalgesia remain incompletely understood. In this study, OIH and spared nerve injury (SNI), a model of peripheral nerve injury, were established in male rats to investigate the similarities and differences in brain activity. Resting-state fMRI and mechanical stimulus task-state fMRI were employed to identify the differential brain regions between those two groups. Both resting-state fMRI and task-state fMRI revealed substantial differences in pain-related functional networks between these two models. Notably, OIH was characterized by a widespread reduction in whole-brain activity, whereas SNI primarily exhibited abnormal activation in specific pain-processing regions. Specifically, enhanced synchrony between the medial parietal association cortex (MPtA) and the ventral posterior thalamic nucleus (VP) was observed in the OIH model, but not in the SNI model. These abnormal changes were further confirmed through <em>in vivo</em> electrophysiological recordings. This study reveals a whole-brain activity responses to resting state and mechanical stimuli in both OIH and SNI models, while also identifying a special thalamo-parietal circuit involved in opioid-induced hyperalgesia. It provides new insights into the neural mechanisms between OIH and SNI, potentially guiding the new strategies for hyperalgesia therapy.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Females show enhanced susceptibility to develop nerve injury and constant joint pain compared to males in a mouse model of knee joint pain","authors":"Madison G. Mueth ,&nbsp;Abigail Del Greco ,&nbsp;Tyler Vesey ,&nbsp;Sebastien Sannajust ,&nbsp;Victoria Eaton ,&nbsp;Peter Caradonna ,&nbsp;Talia Lizotte ,&nbsp;Kathleen A. Becker ,&nbsp;Eliza Grlickova-Duzevik ,&nbsp;Benjamin J. Harrison ,&nbsp;Tamara King","doi":"10.1016/j.ynpai.2026.100209","DOIUrl":"10.1016/j.ynpai.2026.100209","url":null,"abstract":"<div><div>Arthritis is a leading cause of diminished quality of life from chronic pain and disability and is more severe in female patients. Arthritis pain is difficult to manage due to its heterogeneous nature. Patients report joint pain during use that dissipates with joint rest, however some patients also report constant joint pain that fails to abate with rest. A murine model of osteoarthritis knee joint pain was used to explore the hypothesis that constant joint pain is associated with increased nerve injury, and females develop constant pain and nerve injury at earlier stages of joint damage compared to males. Monosodium iodoacetate (MIA) was injected into the intra-articular space of the knee joint followed by analysis of weight asymmetry and analgesia-induced conditioned place preference (CPP) 2 weeks later. Knee joints and dorsal root ganglia (DRG) were collected following behavioral analyses to assess joint pathology, changes in innervation, and nerve injury. Females developed analgesia-induced CPP at a 5-fold lower concentration of MIA (16 mg/mL) compared to males (80 mg/mL), while males treated with 16 mg/mL MIA only developed weight asymmetry. Equivalent joint pathology and changes in innervation were observed in males and females treated with 16 mg/mL MIA despite differences in pain-like behaviors. Increased expression of activating transcription factor-3 (ATF3) mRNA, a marker of nerve injury, was only observed in DRG L2-L5 of females and males with analgesia-induced CPP. These observations indicate that females have increased susceptibility to arthritis associated nerve injury that likely contributes to sex differences in joint pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xpro®1595 alleviates neuropathic pain by targeting spinal dorsal horn ADAM17-mediated inflammation","authors":"Li Li ,&nbsp;Yidie Su ,&nbsp;Ling-ling Sun ,&nbsp;Wei-Wei Yao ,&nbsp;Yan-Yan Sun","doi":"10.1016/j.ynpai.2026.100210","DOIUrl":"10.1016/j.ynpai.2026.100210","url":null,"abstract":"<div><div>A disintegrin and metalloprotease 17 (ADAM17) mediates the shedding of key pro-inflammatory cytokines, yet its specific contribution to neuropathic pain remains elusive. Here, we investigated the role of ADAM17 in the rat spinal nerve ligation (SNL) model. Following nerve injury, ADAM17 expression was significantly upregulated in the spinal dorsal horn (SDH) and dorsal root ganglion (DRG). Specifically, ADAM17 colocalized with TRPV1 and IB4 positive afferents in the superficial SDH, and with IB4, CGRP, and TRPV1 positive neurons in the DRG. Intrathecal administration of exogenous ADAM17 to naive rats recapitulated neuropathic pain behaviors—inducing mechanical and thermal hypersensitivity—and significantly increased the levels of TNF-α, IL-1β, and IL-6 in the SDH. Conversely, therapeutic treatment with Xpro®1595 markedly attenuated SNL-induced pain behaviors. This analgesic effect correlated with the suppression of injury-induced ADAM17 upregulation and a consequent reduction in proinflammatory cytokines. These findings demonstrate that ADAM17 is a critical driver of the neuroinflammatory cascade in neuropathic pain. Moreover, our data suggest that the analgesic efficacy of Xpro®1595 is mediated, at least in part, by disrupting this ADAM17-dependent inflammatory feedback loop.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral immune response and axonal degeneration in the hind paw skin of mice with experimental autoimmune encephalomyelitis","authors":"Andrea G. Klassen ,&nbsp;Timothy N. Friedman ,&nbsp;Gustavo Tenorio ,&nbsp;Jason R. Plemel ,&nbsp;Anna M.W. Taylor ,&nbsp;Bradley J. Kerr","doi":"10.1016/j.ynpai.2025.100207","DOIUrl":"10.1016/j.ynpai.2025.100207","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is traditionally considered a central nervous system (CNS) disease characterized by chronic inflammation and demyelination in the brain and spinal cord, often resulting in debilitating neuropathic pain. While the primary mechanisms of pain in MS are attributed to central mechanisms, recent evidence suggests that peripheral nervous system (PNS) changes may also contribute. Peripheral neurons in the dorsal root ganglia (DRG), which relay sensory information to the CNS, can undergo inflammation-induced structural and functional changes that amplify pain sensitivity. In human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), inflammation and neuronal injury have been observed in the DRG, yet the role of the PNS in MS pain remains underexplored. To investigate peripheral contributions to pain in EAE, we examined disease-induced changes in hind paw cutaneous tissue and found increased inflammation at disease onset that coincided with tactile hypersensitivity. Intraepidermal nerve fiber (IENF) loss was observed in both sexes at disease onset; however, a sex-specific difference in reinnervation emerged by four weeks post-immunization, with females exhibiting significant reinnervation while males did not. These findings identify sex-dependent patterns of peripheral innervation during EAE and raise the possibility that peripheral mechanisms may contribute differently across sexes.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}