Molecular PainPub Date : 2025-01-01DOI: 10.1177/17448069251321143
Mao-Biao Zhang, Jia-Li Chen, Jia-Hui Lu, Gai-Li Jia, Hong Cao, Jun Li
{"title":"SGK1-HDAC4-HMGB1 signaling pathway in the spinal cord dorsal horn participates in diabetic neuropathic pain.","authors":"Mao-Biao Zhang, Jia-Li Chen, Jia-Hui Lu, Gai-Li Jia, Hong Cao, Jun Li","doi":"10.1177/17448069251321143","DOIUrl":"10.1177/17448069251321143","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine whether serum-and glucocorticoid-inducible kinase1 (SGK1) activation-dependent histone deacetylase 4 (HDAC4) phosphorylation, nucleocytoplasmic trafficking, and subsequent regulation of high-mobility group protein box 1 (HMGB1) expression are involved in type 2 diabetic neuropathic pain (DNP).</p><p><strong>Methods: </strong>The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-fat and high-sugar diet for 8 weeks and then fasting them for 12 h, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). SGK1 was inhibited in the spinal cord by intrathecal administration of the SGK1 inhibitor GSK-650394.</p><p><strong>Results: </strong>The present study revealed that pSGK1/tSGK1 was persistently upregulated in the spinal cord of rats with type-2 DNP. The downregulation of pSGK1/tSGK1 through the intrathecal injection of the SGK1 inhibitor GSK-650394 significantly ameliorated the pain hypersensitivity, relieved the abnormal expression of pHDAC4/tHDAC4 and HMGB1, and affected HDAC4 nucleocytoplasmic trafficking in DNP rats.</p><p><strong>Conclusion: </strong>Our data suggest that SGK1 in the spinal cord modulates type-2 DNP by regulating the HDAC4/HMGB1 pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251321143"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374461","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}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-05-07DOI: 10.1177/17448069251342240
Yi-Ming Gu, Xiang Meng, Jia-Yi Liang, Yong Xia, Jun-Wei Huang, Ke Wang, Zi-Yong Ju
{"title":"Electroacupuncture intervention relieves pain by stimulating the STING/IFN-I pathway in rat models of cancer-induced bone pain.","authors":"Yi-Ming Gu, Xiang Meng, Jia-Yi Liang, Yong Xia, Jun-Wei Huang, Ke Wang, Zi-Yong Ju","doi":"10.1177/17448069251342240","DOIUrl":"10.1177/17448069251342240","url":null,"abstract":"<p><p>This study aimed to evaluate the effects of electroacupuncture (EA) on cancer-induced bone pain (CIBP) and investigate its interaction with the STING/IFN-I pathway. A CIBP model was established in female rats. EA was administered for six consecutive days at bilateral L3-L5 Jia Ji points (EX-B2). EA-induced antinociception was evaluated through mechanical, thermal, and cold sensitivity assessments. EA significantly increased the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats with CIBP (<i>p</i> < 0.01). In the spinal cord of CIBP model rats, western blot analysis demonstrated that the application of EA upregulated the expression of STING, IRF3, and IFNAR (<i>p</i> < 0.05). The ELISA results indicated that EA significantly increased the expression of IFN-α (<i>p</i> < 0.005) and IFN-β (<i>p</i> < 0.01) and reduced the expression of TNF-α and IL-1β (<i>p</i> < 0.05). Immunofluorescence analysis revealed that STING was predominantly localized in microglia, with a minimal presence in neuronal cells. Furthermore, intrathecal administration of the STING antagonist C-176 attenuated the analgesic effects of EA in CIBP (<i>p</i> < 0.05). Both EA and STING agonist were effective in alleviating pain in rats with CIBP, possibly through the activation of the STING/IFN-I pathway. Notably, EA treatment reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. In contrast, while the STING agonist exhibited analgesic effects, it was associated with elevated levels of pro-inflammatory cytokines. These finding underscore the therapeutic potential of EA in the management of CIBP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251342240"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990772","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":"Genome-wide association study identifies novel genetic variants associated with widespread pain in the UK Biobank (<i>N</i> = 172,230).","authors":"Qi Pan, Tengda Cai, Yiwen Tao, Luning Yang, Roger Compte, Maryam Kazemi Naeini, Mainul Haque, Tania Dottorini, Frances Mk Williams, Weihua Meng","doi":"10.1177/17448069251346603","DOIUrl":"10.1177/17448069251346603","url":null,"abstract":"<p><strong>Objectives: </strong>Widespread pain is a hallmark characteristic of fibromyalgia, commonly affecting older individuals. This study aimed to identify novel genetic variants associated with widespread pain by utilizing the extensive UK Biobank dataset.</p><p><strong>Methods: </strong>We conducted a primary genome-wide association study (GWAS) using a novel definition of widespread pain, defined as pain experienced all over the body during the past month. Sex-stratified GWAS analysis approach was also performed to analyze the impact of sex on widespread pain.</p><p><strong>Results: </strong>The primary GWAS identified one novel significant genetic locus (rs34691025, <i>p</i> = 1.76 × 10<sup>-8</sup>) on chromosome 5q13.2 within the <i>ARHGEF28</i> gene and several loci that approached genome-wide significance. The sex-stratified GWAS outputs revealed biological difference widespread pain between males and females, with a novel locus identified in the female-specific analysis within the <i>LRMDA</i> gene on chromosome 10. Genetic Correlation analysis demonstrated significant genetic correlations between widespread pain and other phenotypes, including joint disorders and spondylosis. The PheWAS revealed associations between the significant genetic variants with hearing disorders and cardiovascular diseases. A two-sample Mendelian randomization analysis found no significant causal association between hearing loss and widespread pain.</p><p><strong>Conclusions: </strong>Our study advances the understanding of the genetic factors contributing to widespread pain, highlighting notable differences between males and females and identifying a novel genetic locus associated with this condition.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069251346603"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285456","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}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-05-03DOI: 10.1177/17448069251335500
Jinjin Wan, Yujie Ma, Xuanying Chen, Wucheng Tao, Shun Hao, Wujun Geng, Yili Wu, Min Zhuo
{"title":"Characterization of excitatory synaptic transmission in the retrosplenial cortex of adult mice.","authors":"Jinjin Wan, Yujie Ma, Xuanying Chen, Wucheng Tao, Shun Hao, Wujun Geng, Yili Wu, Min Zhuo","doi":"10.1177/17448069251335500","DOIUrl":"10.1177/17448069251335500","url":null,"abstract":"<p><p>The retrosplenial cortex (RSC) plays an important role in navigation, memory and pain. However, there are few studies on excitatory synaptic transmission in the RSC. Here, we used a multi-electrode array recording system (MED64) to study the characteristics of excitatory synaptic transmission in the RSC and the contribution of different types of voltage-gated Ca<sup>2+</sup> channels (VGCCs) in excitatory synaptic transmission. We found that glutamate is the major excitatory transmitter for RSC, and postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors contribute to excitatory synaptic transmission. We also found that the N-type calcium channel blocker ω-conotoxin GVIA (ω-Ctx GVIA) had an inhibitory effect on basal synaptic transmission. The inhibitory effect was not consistent across channels, suggesting the actions effect of N-type VGCCs in RSC was inhomogeneous in spatial distribution. Our findings provide strong evidence that excitatory synaptic transmission in the RSC is mainly mediated by AMPA receptors and that N-type VGCCs mediate fast synaptic transmission in the RSC of adult mice.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251335500"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034271","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}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-05-30DOI: 10.1177/17448069251348778
Lin Liu, Dan-Yang Li, Long-Qing Zhang, Shao-Jie Gao, Fan-He Song, Jia-Yi Wu, Ya-Qun Zhou, Dai-Qiang Liu, Wei Mei
{"title":"Administration of 2-deoxy-D-glucose alleviates cancer-induced bone pain by suppressing microglial polarization to the M1 phenotype and neuroinflammation.","authors":"Lin Liu, Dan-Yang Li, Long-Qing Zhang, Shao-Jie Gao, Fan-He Song, Jia-Yi Wu, Ya-Qun Zhou, Dai-Qiang Liu, Wei Mei","doi":"10.1177/17448069251348778","DOIUrl":"10.1177/17448069251348778","url":null,"abstract":"<p><strong>Background: </strong>Cancer-induced bone pain (CIBP) is a debilitating complication with few effective treatments. Microglial activation contributes to the progression of CIBP. 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor, could inhibit microglial activation. Its effect on CIBP remains unclear. This study aims to investigate the role of 2-DG in CIBP mice and underlying mechanisms.</p><p><strong>Methods: </strong>In this research, we established a CIBP mouse model by injecting Lewis lung cancer (LLC) cells into the bone marrow of the femur. Relevant pain behaviors were assessed by measuring the paw withdrawal threshold and spontaneous hind limb lifting. Additionally, the glycolysis inhibitor 2-DG was intrathecally administered to treat CIBP in mice. Western blotting and immunofluorescence techniques were employed to analyze microglial activation and M1/M2 phenotype markers in the spinal cord.</p><p><strong>Results: </strong>Our findings demonstrated significant microglial activation and polarization toward the M1 phenotype in the spinal cord of CIBP mice. Intrathecal administration of 2-DG effectively alleviated pain-related behaviors in CIBP mice. Furthermore, this treatment suppressed microglial activation and M1 polarization, while significantly restoring levels of the M2 phenotype. Additionally, 2-DG attenuated the production of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while boosting the secretion of the anti-inflammatory factor (IL-10) in the spinal cord of CIBP mice. Notably, 2-DG effectively suppresses microglia activation and M1 polarization in LPS + IFN-γ-induced BV-2 cells by downregulating CD86, iNOS expression, TNF-α, IL-1β, IL-6 levels while upregulating Arg-1, CD206 expression and IL-10 level.</p><p><strong>Conclusion: </strong>These results suggest that 2-DG ameliorates mechanical allodynia, spontaneous pain and neuroinflammation in the spinal cord of CIBP mice by promoting the transition from the M1 phenotype to the M2 phenotype. This study may provide a novel strategy for the treatment of CIBP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251348778"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187421","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}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-05-30DOI: 10.1177/17448069251348770
Hang Xu, Hongtao Lu, Lu Lu, Zhenghao Li, Zhisheng Piao, Yi Jia, Xiaoyan Meng, Feixiang Wu
{"title":"Nanoparticulate MgH<sub>2</sub> suppresses TRPM2-mediated NLRP3 inflammasome to relieve bone cancer pain.","authors":"Hang Xu, Hongtao Lu, Lu Lu, Zhenghao Li, Zhisheng Piao, Yi Jia, Xiaoyan Meng, Feixiang Wu","doi":"10.1177/17448069251348770","DOIUrl":"10.1177/17448069251348770","url":null,"abstract":"<p><strong>Background: </strong>Bone cancer metastases are the third most common site of cancer spread after lungs and liver. This condition often causes severe pain that impairs patients' physical, psychological, and social well-being. We aimed to explore the potential therapeutic benefits of magnesium hydride (MgH<sub>2</sub>) on bone cancer pain (BCP).</p><p><strong>Methods: </strong>A BCP model was established in Wistar rats. Daily oral dosing of 0.5% w/w MgH<sub>2</sub> was administered. Assessment included pain sensitivity, motor coordination, and emotional behaviors. Hippocampal samples underwent RNA sequencing, Western blotting, immunofluorescence, and quantitative RT-PCR.</p><p><strong>Results: </strong>MgH<sub>2</sub> markedly reduced mechanical hypersensitivity and depressive behaviors in rats with BCP. These effects were linked to suppression of the TRPM2-NLRP3 signaling axis in hippocampal microglia. Additionally, MgH<sub>2</sub> served as an adjuvant to reduce opioid tolerance during fentanyl co-treatment, enabling lower opioid dosages. Collectively, MgH<sub>2</sub> inhibited TRPM2 activation, microglial activation, oxidative stress, and NLRP3 inflammasome formation, which together reduced neuroinflammation and improved therapeutic outcomes.</p><p><strong>Conclusion: </strong>MgH<sub>2</sub> nanoparticles may relieve BCP and comorbid depressive symptoms by inhibiting TRPM2-mediated NLRP3 inflammasome activation in hippocampal microglia.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251348770"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187422","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}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-06-04DOI: 10.1177/17448069251350856
Yang Li, Shi-Yu Sun, Tong Liu, Guo-Kun Zhou
{"title":"\"One coin, two aspects\": The role of IGF1R singling in chronic pain.","authors":"Yang Li, Shi-Yu Sun, Tong Liu, Guo-Kun Zhou","doi":"10.1177/17448069251350856","DOIUrl":"10.1177/17448069251350856","url":null,"abstract":"","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251350856"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216403","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":"Depression and anxiety in Chinese patients hospitalized with primary headache: A cross-sectional multicenter study.","authors":"Zhihua Jia, Dongjun Wan, Ziming Yin, Zhiliang Fan, Peng Xu, Xueqian Yuan, Min Chen, Dan Wang, Hebo Wang, Shengshu Wang, Shuhua Zhang, Ruozhuo Liu, Xiaolin Wang, Rongfei Wang, Hui Su, Xun Han, Zhe Yu, Yingji Li, Shengyuan Yu, Zhao Dong","doi":"10.1177/17448069251314271","DOIUrl":"10.1177/17448069251314271","url":null,"abstract":"<p><strong>Background: </strong>Primary headache and psychiatric diseases are bidirectional correlated. The real-world data of depression and anxiety in Chinese patients hospitalized for primary headache, considering all subtypes, remain unclear.</p><p><strong>Methods: </strong>This study enrolled patients attending eight Chinese headache centers from October 2022 to September 2023. A WeChat mini-program was designed to collect data. Headache was diagnosed and confirmed by two headache specialists. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 were used to assess depression and anxiety.</p><p><strong>Results: </strong>Overall, 1963 patients with primary headache were analyzed; the prevalence of depression and anxiety was 20.1% (396/1963) and 14.8% (290/1963), respectively. Of the 1963 patients, 217 (11.1%) had history of anxiety or depression and 184 (9.4%) had undergone assessments. Patients with both primary headache and depression were more likely to be women (77.8% vs 71.9%), experience more severe headache (numerical rating scale; 6.2 ± 1.9 vs 5.7 ± 1.9) and greater impacts on quality of life (Headache Impact Test-6; 65.3± 8.5 vs 58.1 ± 11.5). Those with both primary headache and anxiety exhibited similar results and were less educated. Depression and anxiety were more prevalent in chronic migraineurs (CM) than in episodic migraineurs (36.8% vs 16.9% and 28.9% vs 12.3%, respectively) and in those with chronic (CTTH) than in those with episodic tension-type headache (30.6% vs 15.1% and 20.1% vs 12.8%, respectively).</p><p><strong>Conclusion: </strong>Depression and anxiety are inadequately diagnosed and strongly associated with sex, severe headache, chronification and disability in patients with primary headache in China. To improve the health of patients with primary headaches, early screening for depression and anxiety is important.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251314271"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374458","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":"Puerarin improves the comorbidity of chronic pain and depression by binding with Bax and reducing mitochondrial dysfunction.","authors":"Gege Sheng, Yin Wu, Lixin Yao, Hongyan Liu, Peigen Zhang, Cancan Song, Ganlin Wu, Haili Zhu","doi":"10.1177/17448069251335230","DOIUrl":"10.1177/17448069251335230","url":null,"abstract":"<p><p>Depression is a common comorbidity of chronic pain. The comorbidity of pain and depression causes longer symptoms and poorer patient prognosis. Periaqueductal gray (PAG) is the key region for the regulation of pain and depression. Puerarin (Pue) is a natural isoflavone compound that has a neuroprotective effect, but the mechanisms on the comorbidity of chronic pain and depression remain unclear. In this study, the spared nerve injury (SNI) produced mechanical allodynia and depressive-like behaviors and elevated the neurological damage in ventrolateral (vl) PAG. Meanwhile, at the 8 weeks following injury, mitochondrial dysfunctions including the dysregulated protein levels, the decreased Mn-SOD activity and the reduced ATP contents were observed in vlPAG of SNI model mice. Pue administration improved mechanical pain, motor coordination, and depression-like behaviors, decreased the neuronal activity and neuroinflammation, and elevated the mitochondrial function in vlPAG. Database analysis and experimental assay showed that Pue bound with Bax at the affinity of 2.4 ± 0.1 μM via D102 residue, and decreased Bax level in vlPAG of mice and in primary astrocytic cells. In addition, Pue also recovered levels of mitochondrial membrane potential and reactive oxygen species, and decreased inflammation in primary astrocytic cells. These results suggest that Pue improves the comorbidity of chronic pain and depression by targeting Bax and reducing mitochondrial dysfunction in vlPAG. This study may provide a theoretical basis for Pue application in improving the comorbidity of chronic pain and depression.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251335230"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780662","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}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-06-16DOI: 10.1177/17448069251353346
Sachin Goyal, Nesia Zurek, Reza Ehsanian, Shivali Goyal, David T Jones, Mark Shilling, Gary V Desir, Fred Gorelick, Karin N Westlund, Sascha Ra Alles
{"title":"Visceral pain-related acute actions of cerulein on mouse and human sensory neurons.","authors":"Sachin Goyal, Nesia Zurek, Reza Ehsanian, Shivali Goyal, David T Jones, Mark Shilling, Gary V Desir, Fred Gorelick, Karin N Westlund, Sascha Ra Alles","doi":"10.1177/17448069251353346","DOIUrl":"10.1177/17448069251353346","url":null,"abstract":"<p><p>Cerulein is an orthologue of cholecystokinin, which is often used to induce acute pancreatitis in pre-clinical studies. In these models, animals show signs of pain, and this is the most common complaint of patients with acute pancreatitis. However, little is known about how this pain is mediated, the role of cerulein murine pain responses, or its relevance to human pancreatitis pain. We injected 25 or 50 µg/kg cerulein intraperitoneally into male and female mice and assessed pain behaviors using the von Frey test of mechanical hypersensitivity. The excitability of mouse and human visceral dorsal root ganglia (DRG) neurons was assessed using whole-cell patch-clamp electrophysiology. Pharmacology was performed using commercial antagonists of cholecystokinin (CCK) A or B receptors. We show that pain behaviors developed similarly in male and female cerulein-injected mice and that visceral DRG from these mice exhibited increased excitability compared to controls. Direct application of cerulein to T8-L2 mouse and human DRG showed increased excitability compared to controls consistent with DRG from cerulein-injected mice. The actions of cerulein on visceral DRG neurons were attributed to CCK-A, but not CCK-B receptor. A similar response to cerulein was observed in human thoracic DRG neurons. These findings highlight the importance of the cholecystokinin system, particularly the CCK-A receptor, to visceral pain including pancreatitis through direct sensitization of visceral DRG neurons from mice or humans.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251353346"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310160","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}