Molecular Pain最新文献

{"title":"Zerumbone alleviates TRESK- and TRPV1-mediated ion currents and reduces excitability of human iPSC-derived nociceptor-like neurons.","authors":"Naomi Hoerdler, Angelique Grell, Saheli Chatterjee, Erhard Wischmeyer, Beatrice A Nossek, Oliver Dräger","doi":"10.1177/17448069261492873","DOIUrl":"https://doi.org/10.1177/17448069261492873","url":null,"abstract":"<p><p>Secondary plant metabolites are widely used in traditional and naturopathic medicine to treat pain, infection, and inflammation. The sesquiterpenoid zerumbone, derived from the edible ginger <i>Zingiber zerumbet</i>, has been shown to exert analgesic, antioxidant, antitumoral, and antimicrobial effects in preclinical models, acting through multiple receptor systems including cannabinoid (CB) receptors, peroxisome proliferator-activated receptors, N-methyl-D-aspartate (NMDA) receptors, and the serotonergic system. Zerumbone also modulates inflammatory and nitric oxide-cGMP-K⁺ATP signaling pathways implicated in antiallodynic responses, yet its direct impact on nociceptor-associated ion channels like the Transient receptor potential vanilloid 1 (TRPV1) and the Twik-related spinal cord potassium channel (TRESK) in human cellular systems remains poorly characterized. In the present study, the antinociceptive properties of zerumbone were investigated in human HEK293-based and induced pluripotent stem cell (iPSC)-derived nociceptor models. Here, the zerumbone treatment reduced cell viability and proliferation in a concentration-dependent manner without altering TRPV1 or TRESK protein expression. Whole-cell patch-clamp recordings revealed that zerumbone reversibly inhibited TRESK-mediated outward potassium currents upon direct application, whereas bath-applied zerumbone increased outward currents, suggesting context-dependent modulation. In TRPV1-expressing HEK293 cells, SH-SY5Y neuroblastoma cells, and human iPSC-derived nociceptors, zerumbone reduced TRPV1-mediated ion currents and capsaicin-evoked calcium signals, indicating a direct or competitive inhibitory effect on TRPV1 activity. In iPSC-derived nociceptors, zerumbone decreased action potential firing at moderate depolarizing currents, shifted the resting membrane potential, and increased rheobase, consistent with reduced nociceptor excitability, while no significant changes in TRESK-mediated currents were detected. These data suggest that zerumbone attenuates human iPSC-derived nociceptor-like neuron excitability largely via TRPV1 inhibition, with a more complex, concentration- and application-method-dependent modulation of TRESK. The findings provide a mechanistic basis for the antiallodynic effects of zerumbone observed in rodent models and highlight the need for further studies in human-derived systems to clarify the precise channel-level interactions and their relevance to inflammatory and neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"22 ","pages":"17448069261492873"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137563","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":"Mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in alleviating neuropathic pain in CCI rats.","authors":"Lijuan Yang, Baozhong Yang, Yating Xue, Jun Fang, Chenlong Cui","doi":"10.1177/17448069261417109","DOIUrl":"10.1177/17448069261417109","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a refractory chronic pain disorder with a complex pathogenesis and limited effective treatment options. In recent years, exosomes derived from mesenchymal stem cells (MSC-Exos) have attracted attention as promising therapeutic agents due to their anti-inflammatory, neuroregenerative, and immunomodulatory properties. This study aimed to investigate the therapeutic effects and underlying mechanisms of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. hUC-MSC-Exos were isolated via ultracentrifugation and administered to CCI rats. Behavioral tests demonstrated that hUC-MSC-Exos significantly ameliorated both mechanical allodynia and thermal hyperalgesia in CCI rats. Further mechanistic investigations indicated that hUC-MSC-Exos downregulated the expression of pro-inflammatory cytokines (NF-κB, TNF-α, IL-6) and modulated astrocyte activation and polarization, thereby contributing to neuropathic pain relief. These findings elucidate the potential mechanisms through which hUC-MSC-Exos alleviate NP and provide an experimental foundation for their future clinical application.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261417109"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934450","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":"Transcriptome profiling and experimental validation identify FOS, RAC2, and TYROBP as potential biomarkers for Fu's subcutaneous needling in neuropathic pain treatment.","authors":"Huiqin Fang, Yaping Li, Jiaqi Li, Yarong Sun, Yunhua Zang","doi":"10.1177/17448069261459255","DOIUrl":"10.1177/17448069261459255","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore potential biomarkers and mechanisms underlying in the treatment of neuropathic pain (NP) with Fu's subcutaneous needling (FSN), employing a transcriptomics approach.</p><p><strong>Methods: </strong>In this study, RNA sequencing was performed in a rat model of chronic constriction injury treated with FSN and acupuncture methods. The FSN-related genes in the treatment of NP with FSN were obtained by overlapping the results of differential expression analysis. Potential biomarkers were identified by protein-protein interaction (PPI) analysis and machine learning. In addition, potential biomarkers were analyzed for functional enrichment, molecular regulatory networks, and drug prediction. Reverse transcription quantitative PCR (RT-qPCR) was employed to validate the expression levels of the biomarkers.</p><p><strong>Results: </strong>FOS, RAC2, and TYROBP were identified as potential biomarkers. Furthermore, mo-miR-92a-2-5p was predicted to co-target RAC2 and TYROBP. Twenty-five drugs were predicted to target FOS and four drugs were predicted to target RAC2 were also identified. FSN treatment enhanced and attenuated the expression of RAC2, TYROBP, and FOS, respectively.</p><p><strong>Conclusion: </strong>In this study, FOS, RAC2, and TYROBP were identified as potential biomarkers in the treatment of NP with FSN, providing a potential theoretical basis for NP treatment.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261459255"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157468","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":"Systemic curcumin administration mitigates neuropathic pain in a rat model of trigeminal neuralgia by suppressing TNF-α and pSTAT3 signaling.","authors":"Dara Sari Arini, Lutfi Putra Perdana, Jaime Fabillar, Mayu Miyagi, Daisuke Ikutame, Kazuyuki Koike, Shino Suma, Misaki Ichinomiya, Yoshizo Matsuka, Kosuke Kataoka","doi":"10.1177/17448069261445281","DOIUrl":"10.1177/17448069261445281","url":null,"abstract":"<p><p>Trigeminal neuralgia (TN) is a debilitating neuropathic facial pain disorder characterized by sudden, severe paroxysmal pain that markedly impairs quality of life. Although current pharmacological treatments provide pain relief, their adverse effects highlight the need for safer alternative therapies. Curcumin, a natural polyphenol, exhibits anti-inflammatory and neuroprotective properties with minimal side effects. In this study, we examined the impact of intraperitoneal curcumin administration on the trigeminal ganglia in a TN rat model induced by unilateral infraorbital nerve constriction (IONC). Behavioral tests revealed that curcumin significantly reduced mechanical hypersensitivity compared with vehicle-treated controls. Immunohistochemical analysis showed decreased expression of glial fibrillary acidic protein (GFAP) and activating transcription factor 3 (ATF3), established markers of satellite glial cell (SGC) activation and neuronal stress in the trigeminal ganglia. Furthermore, curcumin administration reduced tumor necrosis factor-α (TNF-α) expression and modulated phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activity. These findings suggest that curcumin alleviates neuropathic pain by suppressing glial activation and pSTAT3-related pro-inflammatory signaling. Curcumin may therefore represent a promising potential therapeutic candidate for TN, warranting further investigation into its clinical applicability and underlying mechanisms.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261445281"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13153540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663089","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":"Interaction of chronic daily headache, dietary intake of iron, and FTO genotype.","authors":"Yeganeh Shekari, Zahra Mahmoodi, Mohammadtaghi Ghorbani Hesari, Parsa Bahmani, Shailin Abdoli Rezaei, Abdolrahman Parhiz, Masoomeh Alsadat Mirshafaei, Fatemeh Sadat Fahimzad, Faezeh Varmazyar, Saeid Doaei, Maryam Gholamalizadeh","doi":"10.1177/17448069261439611","DOIUrl":"10.1177/17448069261439611","url":null,"abstract":"<p><strong>Background: </strong>Chronic daily headache (CDH) is known to be a common and debilitating disease that is influenced by genetic, dietary, and lifestyle factors. Iron (Fe) plays a key role in energy metabolism and neurotransmitter synthesis, while the FTO gene polymorphism (rs9939609) may play a role in modulating nutritional responses and nutrient metabolism. This study aimed to determine the interaction between CDH odds, dietary iron intake, and FTO genotype.</p><p><strong>Methods: </strong>This case-control study was conducted on 150 CDH patients and 150 healthy individuals aged 40-80 years. Participants were assessed for anthropometric measurements, assessment of food intake using a validated food frequency questionnaire, and FTO genotype. The association between dietary iron intake and CDH stratified by FTO genotype was assessed using logistic regression analysis after adjusting for age, gender, body mass index (BMI), physical activity, energy intake, and hypertension.</p><p><strong>Results: </strong>Among individuals with AT/AA genotypes, those with CDH had lower dietary iron intake than controls (17.10 ± 4.02 vs 18.63 ± 4.62 mg/day, <i>p</i> = 0.023). Logistic regression after full adjustment found an inverse association between dietary iron and CDH in AT/AA genotype carriers (<i>p</i> = 0.042). No significant association was observed in TT genotype carriers.</p><p><strong>Conclusion: </strong>Dietary iron intake may be associated with a reduced odds of CDH in FTO A allele carriers, but no association was observed in TT genotype carriers, suggesting a gene-nutrient interaction in the prevention and management of CDH. Further studies are necessary to substantiate these findings.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261439611"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513679","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":"Therapeutic modulation of pain-related affective disorders by acupuncture: Mechanistic review.","authors":"Hongchun Xiang, Yiwen Long, Siyi Wang, Bingkun Li, Yawen Deng, Rongxuan Zhou, Jin Zhang, Man Li, Jing Li","doi":"10.1177/17448069261441012","DOIUrl":"10.1177/17448069261441012","url":null,"abstract":"<p><p>This review reexamines the mechanism by which acupuncture (especially electroacupuncture) modulates pain-related affective disorders from an integrative functional framework. We propose that the efficacy of acupuncture stems from its regulatory functions that mobilize and coordinate multiple internal physiological systems at the same time. Specifically, it is mainly realized through five functional modules: (1) central network remodeling function: correcting abnormal functional connections and neural circuit activity in brain regions related to pain and emotion; (2) Neuroplasticity and repair function: activate neurotrophic pathways and synaptic regulatory mechanisms to promote neural adaptation; (3) Systematic homeostasis regulation function: balancing the interaction of neurological-endocrine-gut axes; (4) Nociceptive signal gating function: a common signaling pathway that accurately inhibits pain and negative emotions at the molecular and receptor levels; (5) Neuroimmune regulatory function : targeted inhibition of central-specific inflammatory pathways and cytokine storms. This article aims to systematically summarize the evidence from the past 5 years and clarify how these five functions constitute a synergistic treatment network, providing a new perspective for the clinical application and mechanism research of acupuncture.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261441012"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13153491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691061","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":"EXPRESS: Evaluation of Stress Biomarkers in individuals with Migraine or Tension-Type headached before and after Botulinum Toxin Injection.","authors":"Afrah Abdulsahib Abbas, Fawaz Aswad, Taghreed Zaidan","doi":"10.1177/17448069251410747","DOIUrl":"https://doi.org/10.1177/17448069251410747","url":null,"abstract":"<p><p>Migraine is a very common and incapacitating condition. We chose to assess the therapeutic effect of Botulinum toxin injection on migraine and tension-type headache patients in an effort to measure salivary alpha amylase for these groups before and after treatment with Botulinum toxin injection because stress appears to be a significant provoking factor of this disorder.There were twenty patients with chronic tension-type headaches and twenty-five patients with chronic migraines among the forty-five individuals. Enzyme-linked immunosorbent assay (ELISA) kits were used to test the salivary biomarker (salivary cortisol and salivary alpha amylase). The PREEMPT (Onabotulinum toxinS AntIpOde for chronic migraiNe) treatment protocol, a systematic procedure for treating chronic migraines, was administered to the patients. Biomarkers measured during the study were analyzed as surrogate measures of stress to shed light on potential physiological action of the intervention. Context In patients with chronic migraine and tension-type headaches, the effect of Nabota (Botulinum toxin type A) on specific stress-related indicators was evaluated.The results demonstrated a statistically significant (p<0.05) rise in salivary cortisol and a statistically significant (p<0.05) decrease in salivary alpha amylase following Botulinum toxin intervention for both research groups (chronic migraine, chronic tension headaches).</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251410747"},"PeriodicalIF":2.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743378","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":"EXPRESS: Dehydrocorydaline can be a suitable candidate for analgesic purposes: a review on the current preclinical evidence.","authors":"Mehdi Dehghani, Behrang Nooralishahi, Fatemeh Rezaee Tazangi","doi":"10.1177/17448069251380033","DOIUrl":"10.1177/17448069251380033","url":null,"abstract":"<p><p>Pain stands as one of the main factors related to human disability and suffering, with different classifications (e.g., acute/chronic, somatic/visceral, and malignant/non-malignant). The management of this factor is of great importance during the lifespan; however, the current suggested medications have not yet reflected sufficient effectiveness with minimum side effects. Therefore, applying an ideal strategy against conditions accompanied by pain is urgent. A growing body of evidence has recently highlighted that alkaloids as bioactive compounds with analgesic capacity can be effective in these conditions. Regarding this matter, dehydrocorydaline, a bioactive alkaloid derived from the tubers of Rhizoma Corydalis, has shown promising results in pain management in diseases, including Chronic constriction injury, bone cancer, sleep deprivation, and inflammatory pain. Also, dehydrocorydaline has been shown to exert different biological and pharmacological benefits, like anti-tumor, anti-inflammatory, anti-microbial, anti-viral, anti-nociceptive, and cardioprotective. Hence, in this literature review, we aimed to explore the potential of this alkaloid agent in these conditions with a mechanistic insight.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251380033"},"PeriodicalIF":2.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006331","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":"EXPRESS: Honokiol and analgesia: a mechanistic review on the current capacities and challenges.","authors":"Behrang Nooralishahi, Mehdi Dehghani, Fatemeh Rezaee Tazangi","doi":"10.1177/17448069251377447","DOIUrl":"10.1177/17448069251377447","url":null,"abstract":"<p><p>Pain is an unfavorable subjective sensation influencing 20% of the public population, giving rise to substantial health and economic issues. Several categories of pain, such as acute and chronic pain, have been determined according to factors like pathophysiological mechanism, etiology, and anatomical locations. The current analgesic drugs are the cornerstone of pain management; however, some challenges, such as short-term relief and concerns about addiction, dependence, and side effects, warrant alternative choices for pain alleviation. In the recent decade, the importance of polyphenolic compounds, particularly honokiol, has increased due to their diverse therapeutic and biological features like anti-cancer, anti-inflammatory, anti-oxidative, anti-bacterial, anti-viral, and immune regulatory properties. Also, some documents have accentuated the striking role of honokiol in exerting analgesic effects in conditions such as inflammatory pain, neuropathic pain, and gouty arthritis. Ergo, the current literature review aimed to discuss the analgesic potential of honokiol in the mentioned conditions with a mechanistic insight.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251377447"},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962119","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":"Targeting sphingosine-1-phosphate receptor 1 alleviates neuropathic pain associated with pancreatic ductal adenocarcinoma in mice and inhibits tumor progression.","authors":"Shen-Quan Cai, Yi-Xuan Zhang, Chun Wang, Yu Gao, Ting-Yu Wang, Fang-Ning Xu, Qing-Zheng Liu, Jing Yin, Zhi-Jie Zhang, Shu Zhang, Muan-Lin Duan, Ying Huang, Gao-Jian Tao","doi":"10.1177/17448069251371549","DOIUrl":"10.1177/17448069251371549","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic neuropathy occurs during the development of pancreatic ductal adenocarcinoma (PDAC), with changes correlating to pancreatic neuropathic pain and increased expression of nociceptive genes in sensory ganglia. Emerging evidence suggests that sphingosine-1-phosphate receptor 1 (S1PR1) plays critical roles in the onset and maintenance of pain. However, whether S1PR1 in sensory ganglia contributes to PDAC-associated neuropathic pain remains unclear.</p><p><strong>Methods: </strong>We collected histopathological sections and pain-related data from patients who underwent surgical resection and were pathologically confirmed as having PDAC. S1PR1 levels in intrapancreatic nerves were measured using immunohistochemistry. A mouse model of PDAC-associated pain was established in C57BL/6J mice via orthotopic transplantation of MT5 cells. Pain behaviors were evaluated through abdominal mechanical hyperalgesia, hunch score, and open-field tests. The changes and subcellular localization of S1PR1 in dorsal root ganglia (DRGs) were observed. Subsequently, the S1PR1 antagonists W146 and FTY720 were administered to investigate the underlying molecular mechanisms. We further assessed the analgesic efficacy and its impact on tumor progression of the S1PR1 antagonist FTY720.</p><p><strong>Results: </strong>S1PR1 levels in nerves from PDAC patients experiencing cancer-associated pain were significantly higher compared to those without such pain. In the DRGs of a PDAC mouse model, S1PR1 expression was upregulated and colocalized with neurons and satellite glial cells. Intrathecal injection of S1PR1 antagonists W146 and FTY720 effectively alleviated PDAC-induced neuropathic pain hypersensitivity and suppressed the upregulation of transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP). Additionally, FTY720 alleviated pancreatic cancer-related neuropathic pain and demonstrated partial anti-tumor effects.</p><p><strong>Conclusions: </strong>Our findings indicate that S1PR1 in DRGs plays a pivotal role in PDAC-associated neuropathic pain. Inhibition of S1PR1 signaling may alleviate PDAC-related neuropathic pain, and targeting S1PR1 represents a promising strategy for adjuvant management of pancreatic cancer-related pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251371549"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847626","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}