Molecular Pain最新文献

{"title":"Orbital tightening assessment to evaluate pain and physical discomfort in chlorine-exposed rats: A machine learning based measurement approach.","authors":"Saurav Gupta, Wesam Nasser, Gajanan R Jadhav, Amber J Johns, Iram Zafar, Aftab Ahmad, Jianguo Gu, Shama Ahmad","doi":"10.1177/17448069251410828","DOIUrl":"10.1177/17448069251410828","url":null,"abstract":"<p><p>Noxious chemicals like chlorine induce extreme distress, pain, and irritation in exposed individuals, yet methods to evaluate pain-related behavioral responses are absent. It is also unknown whether analgesics would alleviate pain and physical discomfort induced by such noxious chemicals. The grimace scale (GS), which evaluates facial expression features such as orbital tightening (OT), is a valuable indicator of pain and distress in animals. However, conventional GS approaches are labor-intensive, prone to subjectivity, and lack quantitative precision. In this study, we employed machine learning with DeepLabCut to annotate key facial landmarks in video recordings of chlorine-exposed rats. Focusing on the superior and inferior eyelid margins and the medial and lateral canthi, we quantified eyelid distance and palpebral fissure width as measures of OT. Rigorous inclusion and exclusion criteria for annotated images were established to ensure accuracy and reproducibility. The quantitative GS in rats subjected to chlorine exposure was validated. Significant reductions in eyelid distance and palpebral fissure width were observed upon chlorine exposure as compared to unexposed control animals. Administration of the opioid analgesic buprenorphine significantly reduced the OT caused by chlorine. This study establishes a robust, quantitative method for assessing OT in chlorine-exposed rats using DeepLabCut, providing a scalable, objective tool for assessing pain induced by noxious chemicals in preclinical research. This study also suggests that opioids can alleviate pain and physical discomfort induced by inhalation of noxious chemicals, providing a new therapeutic strategy for managing the respiratory hazard of noxious chemicals.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251410828"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12812198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743391","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":"Corrigendum to \"Copper chelator ammonium tetrathiomolybdate ameliorates the visceral hypersensitivity in dextran sulfate sodium-induced colitis mice\".","authors":"","doi":"10.1177/17448069261462699","DOIUrl":"10.1177/17448069261462699","url":null,"abstract":"","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261462699"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308887","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":"Mitochondrial DAMPs produce inflammatory hyperalgesia via stimulator of interferon genes (STING) activation in DRG neurons.","authors":"Hiroaki Amino, Ayaka Higashi, Shunsuke Yamakita, Yasuhiko Horii, Fumimasa Amaya","doi":"10.1177/17448069261435322","DOIUrl":"10.1177/17448069261435322","url":null,"abstract":"<p><p>Damage-associated molecular patterns (DAMPs), including mitochondria-derived molecules, are known to trigger immune responses and produce nociceptor sensitization during tissue inflammation. This animal study investigated whether mitochondrial debris promotes inflammatory hyperalgesia through activation of the stimulator of interferon genes (STING) signaling pathway in dorsal root ganglion (DRG) neurons. The results showed that local administration of mitochondrial debris into the hind paws of rats induced significant mechanical hyperalgesia and increased STING expression in DRG neurons. Pretreatment with H-151, a selective STING inhibitor, attenuated both debris-induced hyperalgesia and neuronal STING upregulation. STING expression in DRG neurons was similarly upregulated in a model of tissue inflammation induced by Complete Freund's Adjuvant (CFA), and administration of H-151 significantly alleviated the inflammatory hyperalgesia and increase in STING expression. These findings suggest that mitochondrial debris released during tissue inflammation activates the STING pathway in primary afferent neurons. Effective suppression of hyperalgesia by pharmacological inhibition of STING in both debris-induced and CFA-induced models in this study highlights the pronociceptive role of STING activation in peripheral sensory neurons. In conclusion, mitochondrial debris-induced STING activation in DRG neurons plays a critical role in the development of inflammatory hyperalgesia, and targeting this pathway might represent a novel therapeutic strategy for inflammatory pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261435322"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444270","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":"Mechanism of asiatic acid in relieving psoriasis by modulating the PI3K/Akt/NF-κB pathway and NLRP3 inflammasome.","authors":"Juan Wang, Mukadas Dilishti, Fang Wang, Tungchun Lee, Mengzhuang Liu","doi":"10.1177/17448069261435785","DOIUrl":"10.1177/17448069261435785","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this paper is to expound the effect of asiatic acid (AA) on psoriasis via modulating the PI3K/Akt/NF-κB pathway and NLRP3 inflammasome.</p><p><strong>Methods: </strong>An imiquimod (IMQ)-induced psoriasis model in BALB/c mice was established. Mice were divided into the control, IMQ, and AA treatment groups with different doses. Psoriasis area and severity were scored using the Psoriasis Area Severity Index (PASI). Histological changes, inflammatory factor levels in skin lesions, and expressions of NLRP3 inflammasome-related proteins and pathway proteins were measured. For cellular experiments, HaCaT cells were classified into control, model, AA low and high concentration groups, and AA-H + IGF group. Cells were stimulated with IL-17A, IL-22, TNF-α, IL-1α, and OSM (M5) to induce psoriasis-like conditions, followed by treatment with AA or IGF. Cell viability, oxidative stress levels, inflammatory factors, NLRP3 expression, and PI3K/Akt/NF-κB pathway protein levels were assessed.</p><p><strong>Results: </strong>In vivo, IMQ-induced mice showed psoriasis-like symptoms, including increased PASI scores, IL-6, TNF-α, IL-17A, and NLRP3-related protein levels. AA treatment alleviated these symptoms, reducing NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression, and restraining the PI3K/Akt/NF-κB pathway phosphorylation. In cellular experiments, M5 induction impeded cell viability and advanced oxidative stress, IL-1β, IL-6, and NLRP3 expression, activating the PI3K/Akt/NF-κB pathway. AA markedly reversed these change.</p><p><strong>Conclusion: </strong>AA alleviates psoriasis symptoms by blocking the PI3K/Akt/NF-κB pathway and NLRP3 inflammasome.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261435785"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13153537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444202","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":"Assessment of pruritogen-induced responses in the glabrous skin of mice.","authors":"Shuang Wu, Haley Steele, Katy Lawson, Ryan Stewart, Liang Han","doi":"10.1177/17448069261420554","DOIUrl":"10.1177/17448069261420554","url":null,"abstract":"<p><p>Chronic itch is a debilitating symptom associated with many dermatological and systemic diseases. Rodent behavioral models that distinguish pain and itch responses remain limited. Our previous studies have examined behavioral responses of mice to chemicals delivered to the plantar glabrous skin and suggested that glabrous skin biting is associated with itch sensation whereas licking represents pain sensation, establishing a new mouse behavioral model to differentiate pain and itch responses in the glabrous skin. To provide further validation of this model, we here investigated behavioral responses following intraplantar injection of multiple pruritogens to examine if they can effectively evoke biting behavior. We show that most of the tested pruritogens induced dose-dependent responses. PAR2 peptide agonist SLIGRL selectively evoked licking, whereas deoxycholic acid (DCA) selectively induced biting. 5-HT triggered licking with a low concentration and both licking and biting with a higher concentration. IL-31, allergen ovalbumin, and mast cell degranulator compound 48/80 evoked both licking and biting. Importantly, morphine abolished capsaicin-induced licking but not biting induced by Bam8-22 or DCA, confirming that glabrous skin biting represents an itch-associated nocifensive behavior. Together, our results establish a robust model to differentiate between pain and itch and provide a platform for investigating mechanisms underlying glabrous skin itch.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261420554"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041445","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":"Cimifugin alleviates chronic inflammatory pain by inhibiting neuroinflammation and restoring synaptic function: A network pharmacology and in vivo study.","authors":"Hanyu Lei, Zheng Rong, Guan Liu, Le Yang, Minggao Zhao","doi":"10.1177/17448069261488527","DOIUrl":"10.1177/17448069261488527","url":null,"abstract":"<p><p>BackgroundChronic inflammatory pain has a high incidence, and existing drugs have side effects. The natural product Cimifugin has anti-inflammatory and analgesic potential, but its role and mechanism in treating chronic inflammatory pain remain unclear. This study aims to explore the potential targets, signaling pathways, and in vivo mechanism of Cimifugin in the treatment of chronic inflammatory pain.MethodsNetwork pharmacology was used to predict the potential targets and related pathways of Cimifugin. A mouse model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) was established. Behavioral tests (mechanical/thermal hyperalgesia, elevated plus maze) were conducted to evaluate pain sensation and anxiety-like behaviors. ELISA was used to detect inflammatory factors (IL-1β, IL-6, TNF-α). Western blot was employed to analyze synaptic functional proteins. HPLC-MS/MS was used to verify Cimifugin's ability to cross the blood-brain barrier.ResultsNetwork pharmacology analysis predicted that the 64 cross-targets of Cimifugin and chronic inflammatory pain are enriched in pathways such as MAPK and PI3K-Akt. Animal experiments showed that Cimifugin dose-dependently increased pain thresholds, reduced paw swelling, improved anxiety-like behaviors, decreased inflammatory factor levels, reversed abnormal expression of synaptic functional proteins, and could cross the blood-brain barrier.ConclusionCimifugin alleviates chronic inflammatory pain and related behavioral abnormalities, an effect associated with inhibition of inflammatory responses and restoration of synaptic protein expression. These findings suggest a multi-target, multi-pathway mechanism of action.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261488527"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930635","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":"CB₁ antinociceptive tolerance is delayed in S426A/S430A mice and accelerated in older mice in the formalin test of inflammatory pain.","authors":"Robert C Barnes, Hannah Quick, Satish Banjara, Dakota Robison, Aric F Logsdon, Josée Guindon","doi":"10.1177/17448069261489964","DOIUrl":"https://doi.org/10.1177/17448069261489964","url":null,"abstract":"<p><p>Inflammatory pain represents a significant detriment to patient quality of life and currently lacks adequate treatment options. Conditions associated with inflammatory pain can occur across the lifespan but are most common in aged individuals. There has been increasing public interest in the analgesic potential of cannabinoids, and CB₁ agonists have been preclinically tested for several conditions. However, their use is potentially limited by the development of tolerance. The S426A/S430A transgenic mouse line was previously generated to explore this tolerance, with two point mutations preventing the phosphorylation that represents the first step in CB₁ desensitization. Therefore, we investigated the antinociceptive efficacy of CB₁-selective agonism (ACEA) in the formalin model of inflammatory pain, using mice that varied in sex (female vs male), age (3- vs 12-month-old [MO], and genotype (C57BL/6J vs S426A/S430A). ACEA provided significant antinociception that was equivalent across all tested group. The S426A/S430A mutation significantly delayed tolerance at both ages tested. Additionally, the S426A/S430A mutation was associated with increased body weight in 3MO, 12MO female, and 12MO male mice. Mice that were 12MO had accelerated tolerance relative to 3MO mice. No significant differences in rotarod (motor coordination), open field (locomotion and center duration), or rectal temperature were noted. These results demonstrate the antinociceptive benefit of CB₁ agonists and the significant limitation in their use (tolerance). Further studies are needed to investigate the mechanisms of CB₁ tolerance development, the increase in body weight with the S426A/S430A mutation, and the potential clinical significance of these findings.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261489964"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of acetylation-related molecular signatures in knee osteoarthritis patients with significant response to warm-needle acupuncture using machine-learning approaches.","authors":"Jiqing Wang, Bo Xu, Da-Eun Yoon, Shifen Xu, Shangjun Xia, Junjie Xu, Xiaoqin Fang, Haiyi Wu, Younbyoung Chae, Yiqun Mi","doi":"10.1177/17448069261439615","DOIUrl":"10.1177/17448069261439615","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to characterize the remodeling of acetylation-related gene expression in knee osteoarthritis (KOA) patients with a marked response to warm-needle acupuncture (WNA) and to identify key genes and underlying immunoregulatory mechanisms.</p><p><strong>Methods: </strong>In this prospective self-paired study, 34 KOA patients were recruited, and whole-blood samples were collected before and after WNA treatment for transcriptome sequencing. Differential expression analysis identified acetylation-related genes followed by enrichment and protein-protein interaction analyses. Key genes were extracted via feature selection based on LASSO and SVM-RFE methods and further used to establish and validate a multigene logistic regression model. Consensus clustering was used to identify two acetylation subtypes (ACEcluster A/B), and their immune characteristics were further explored by ssGSEA and immune-cell infiltration profiling.</p><p><strong>Results: </strong>After treatment, acetylation-related genes were globally upregulated and were enriched in protein acetylation and acetyltransferase complex pathways. Further, four genes (SPRED1, HDAC3, NSRP1, and DUSP1) exhibited stable performance and were further used to build a nomogram and achieve high discriminative performance (AUC = 0.908 in the training set; 0.810 in the validation set). Subtype B displayed higher acetylation activity and immune-cell infiltration. Co-expression analysis on 452 acetylation-related genes extracted 107 highly co-regulated candidates and further clustered into two groups coinciding with ACEcluster classification.</p><p><strong>Conclusion: </strong>WNA markedly remodels the peripheral-blood acetylation-related transcriptomic network in KOA and suggests that stronger acetylation activity is associated with immune-cell activation. The four-gene nomogram provides both mechanistic insights and a potential tool for individualized prediction of WNA efficacy.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261439615"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513749","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":"Spinal microglia mediate chronic itch by promoting ferroptosis.","authors":"Zhao-Ting Li, Guang-Yi Si, Qi Dai, Min Zhang, Xiao-Na Bu, Ji-Yun Peng, Shun-Qi Wang, Chong Sun, Min Yuan, Bao Xue, Chao-Lin Ma, Hai-Li Pan","doi":"10.1177/17448069261495308","DOIUrl":"https://doi.org/10.1177/17448069261495308","url":null,"abstract":"<p><p>Chronic itch, affecting 8-10% of the global population, is a debilitating condition linked to dermatoses, systemic diseases, and neurological disorders, with limited therapeutic efficacy due to unclear central mechanisms. Spinal microglia, central nervous system-resident immune cells, regulate neuroinflammation and synaptic plasticity in chronic pain and neurodegeneration, but their role in chronic itch remains unknown. This study investigated the role of spinal microglia in chronic itch. Using an allergic contact dermatitis (ACD) mouse chronic itch model, we found robust microglial activation, accompanied by c-Fos-positive neuronal activation, in the spinal dorsal horn of a chronic itch model. Pharmacological inhibition (minocycline) or genetic ablation of microglia significantly reduced mechanical itch hypersensitivity and spontaneous scratching, alongside decreased microglial/neuronal activation. Morphological and molecular analyses revealed downregulated antioxidants (glutathione peroxidase 4 [GPX4], superoxide dismutase [SOD], glutathione [GSH],) and upregulated lipid peroxidation (malondialdehyde [MDA], acyl-CoA synthetase long-chain family member 4 [ACSL4]) in the spinal cord, indicating ferroptosis. Intrathecal liproxstatin-1 (ferroptosis inhibitor) alleviated itch behaviors and restored GPX4, SOD, GSH and MDA level, without affecting microglial activation. Our findings demonstrate that spinal microglia promote chronic itch by triggering ferroptosis in spinal dorsal horn. These findings provide the first evidence of microglia-ferroptosis crosstalk in chronic itch, providing a mechanistic basis for targeting glial activity or ferroptosis to develop novel therapies.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261495308"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper chelator ammonium tetrathiomolybdate ameliorates the visceral hypersensitivity in dextran sulfate sodium-induced colitis mice.","authors":"Lei Gao, Ruiyu Wang, Jingting Zhou, Shiqin Xu, Shanwu Feng, Liping Zhao, Chunyi Jiang, Xian Wang","doi":"10.1177/17448069261428972","DOIUrl":"10.1177/17448069261428972","url":null,"abstract":"<p><strong>Background: </strong>Visceral hypersensitivity is a prevalent and debilitating symptom in inflammatory bowel disease (IBD), severely impairing quality of life. Although mechanisms remain incompletely understood, recent studies have reported abnormal copper metabolism and elevated serum copper in IBD patients. However, whether copper homeostasis contributes to visceral hypersensitivity remains unknown.</p><p><strong>Methods: </strong>We established a dextran sulfate sodium (DSS)-induced colitis model in C57BL/6J mice to induce visceral hypersensitivity. Copper content in the terminal colon and dorsal root ganglia (DRG) was measured using a colorimetric copper assay kit. Western blot analysis evaluated expression of central sensitization markers, calmodulin-dependent kinase II (CaMKII), phosphorylated CaMKII (p-CaMKII), cyclic adenosine monophosphate response element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the spinal cord and DRG. The expression of cuproptosis-related proteins, including dihydrolipoamide S-acetyltransferase (DLAT), lipoic acid synthetase (LIAS), and ferredoxin 1 (FDX1), was also measured in the terminal colon and DRG. We examined the effects of the copper chelator ammonium tetrathiomolybdate (ATTM, 10 mg/kg, i.p., daily). Expression of copper transport ATPase copper transporting alpha (ATP7A) and copper transporter 1 (CTR1) was also assessed.</p><p><strong>Results: </strong>DSS-induced colitis resulted in visceral hypersensitivity and central sensitization, accompanied by copper accumulation in the terminal colon and DRG, along with downregulation of DLAT, LIAS, and FDX1. ATTM reduced copper accumulation, restored cuproptosis-related protein expression, and attenuated visceral hypersensitivity and central sensitization. Notably, ATTM normalized the expression of the copper efflux transporter ATP7A and the influx transporter CTR1 in the terminal colon and DRG.</p><p><strong>Conclusion: </strong>Our findings for the first time definitely identify and mechanistically elucidate that copper accumulation in the terminal colon and DRG contributes to visceral hypersensitivity in DSS-induced colitis. Dysregulation of the copper transporters ATP7A and CTR1 underlies this copper dyshomeostasis. Our results uncover copper ion homeostasis as a completely unrecognized, novel mechanistic axis driving visceral hypersensitivity in IBD.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261428972"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259086","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}