Molecular Pain最新文献

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Administration of 2-deoxy-D-glucose alleviates cancer-induced bone pain by suppressing microglial polarization to the M1 phenotype and neuroinflammation. EXPRESS: 2-脱氧-d -葡萄糖通过抑制M1表型和神经炎症的小胶质细胞极化来减轻癌症引起的骨痛。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-05-30 DOI: 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}
引用次数: 0
Nanoparticulate MgH2 suppresses TRPM2-mediated NLRP3 inflammasome to relieve bone cancer pain. 表达:纳米颗粒MgH 2抑制trpm2介导的NLRP3炎性体缓解骨癌疼痛。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-05-30 DOI: 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}
引用次数: 0
"One coin, two aspects": The role of IGF1R singling in chronic pain. EXPRESS:“一枚硬币,两个方面”:IGF1R单链在慢性疼痛中的作用。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-06-04 DOI: 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}
引用次数: 0
Depression and anxiety in Chinese patients hospitalized with primary headache: A cross-sectional multicenter study. 中国原发性头痛住院患者的抑郁和焦虑:一项横断面多中心研究。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 DOI: 10.1177/17448069251314271
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
{"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}
引用次数: 0
Puerarin improves the comorbidity of chronic pain and depression by binding with Bax and reducing mitochondrial dysfunction. EXPRESS:葛根素通过与Bax结合和减少线粒体功能障碍改善慢性疼痛和抑郁的合并症。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-04-04 DOI: 10.1177/17448069251335230
Gege Sheng, Yin Wu, Lixin Yao, Hongyan Liu, Peigen Zhang, Cancan Song, Ganlin Wu, Haili Zhu
{"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}
引用次数: 0
Visceral pain-related acute actions of cerulein on mouse and human sensory neurons. 表达:蓝核蛋白对小鼠和人类感觉神经元的内脏痛相关急性作用。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-06-16 DOI: 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}
引用次数: 0
Curcumin relieves CFA-induced inflammatory pain by inhibiting the AP-1/c-Jun-CCL2-CCR2 pathway in the spinal dorsal horn. EXPRESS:姜黄素通过抑制脊髓背角AP-1/c-Jun-CCL2-CCR2通路缓解cfa诱导的炎性疼痛。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 DOI: 10.1177/17448069251323668
Yi Zhu, Yinhong Jiang, Xinyu Lu, Siyu Li, Fujiaying Liu, Yidan Xu, Yue Tian, Liangliang Gao, Lei Wei
{"title":"Curcumin relieves CFA-induced inflammatory pain by inhibiting the AP-1/c-Jun-CCL2-CCR2 pathway in the spinal dorsal horn.","authors":"Yi Zhu, Yinhong Jiang, Xinyu Lu, Siyu Li, Fujiaying Liu, Yidan Xu, Yue Tian, Liangliang Gao, Lei Wei","doi":"10.1177/17448069251323668","DOIUrl":"10.1177/17448069251323668","url":null,"abstract":"<p><p>Inflammatory pain is a pervasive clinical issue that severely diminishes individuals' quality of life. AP-1 (Activating protein-1) is a transcription factor composed of Jun and Fos proteins. Upregulation of AP-1/c-Jun activity is observed in a variety of diseases, particularly in inflammatory conditions. The CCL2 (C-C Motif Chemokine Ligand 2)/CCR2 (C-C Chemokine Receptor 2) axis plays a crucial role in regulating both peripheral and central inflammation. Curcumin, a natural compound derived from the roots of turmeric, possesses anti-inflammatory, antioxidant, and analgesic properties, making it effective for treating various disorders. However, the effects of curcumin on inflammatory pain and its potential mechanisms of action remain unclear. In this study, we utilized a CFA (Complete Freund's Adjuvant)-induced inflammatory pain model to investigate the effects of curcumin. We found that curcumin effectively reduced CFA-induced mechanical allodynia when administered via intrathecal injection. Behavioral assessments were performed using the Von Frey test. Western blot analysis was performed to detect variations in molecular expression, while immunofluorescence was employed to ascertain cellular localization. Intrathecal injection of the AP-1/c-Jun inhibitor T-5224, along with curcumin, resulted in a reduction in the levels of c-Jun, p-c-Jun, CCL2, and CCR2. Additionally, intrathecal injection of the CCR2 antagonist RS504393 also reduced the expression of CCL2 and CCR2. In summary, curcumin plays a significant role in analgesia within the CFA-induced inflammatory pain model. CCL2/CCR2 acts as a downstream mediator of AP-1/c-Jun. Curcumin can suppress the expression of AP-1/c-Jun, thereby inhibiting the expression of CCL2 and CCR2 in the spinal dorsal horn and contributing to the treatment of inflammatory pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251323668"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414630","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}
引用次数: 0
TLR3 mediates central sensitization in a chronic migraine model induced by repeated nitroglycerin through the ERK signaling pathway. EXPRESS: TLR3通过ERK信号通路介导反复硝酸甘油诱导的慢性偏头痛模型的中枢致敏。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-05-23 DOI: 10.1177/17448069251346373
Bin Yang, Zhaoming Ge
{"title":"TLR3 mediates central sensitization in a chronic migraine model induced by repeated nitroglycerin through the ERK signaling pathway.","authors":"Bin Yang, Zhaoming Ge","doi":"10.1177/17448069251346373","DOIUrl":"10.1177/17448069251346373","url":null,"abstract":"<p><strong>Background: </strong>Studies have demonstrated that Toll-like receptor 3 (TLR3) plays a crucial role in neuropathic pain. However, there have been no relevant reports regarding the role of TLR3 in migraine chronification. This study aims to investigate the molecular mechanisms of TLR3 in the central sensitization of chronic migraine (CM).</p><p><strong>Methods: </strong>C57BL/6 male mice were used as models for chronic migraine (CM) disease, receiving an intraperitoneal injection of nitroglycerin (NTG) every other day. Calibrated von Frey filaments were employed to measure the pain threshold in the hind paw sole and periorbital region, enabling the assessment of mechanical allodynia. Western blot was employed to detect the expression changes of TLR3, TRAF6, TAK1, c-Fos, calcitonin gene-related peptide (CGRP), and the extracellular signal-regulated kinase (ERK) signaling pathway. Immunofluorescence was used to detect the cellular localization of TLR3 and the expression changes of central sensitization-related indicators, such as c-Fos and CGRP. In addition, we investigated the effects of TLR3 inhibitor (CU CPT4a), MEK inhibitor(PD98059), TRAF6 inhibitor(C25-140), and TAK1 inhibitor (Takinib) on chronic migraine-like behavior, and activation of the ERK pathway in the Trigeminal nucleus caudalis (TNC).</p><p><strong>Results: </strong>Recurrent injections of NTG resulted in a significant increase in the expression of TLR3, TRAF6, TAK1, CGRP, and c-Fos proteins, as well as the activation of the ERK signaling pathway. Concurrent inhibition of TLR3 function, TRAF6, TAK1, and the ERK pathway counteracted these changes and alleviated hyperalgesia in CM mice.</p><p><strong>Conclusions: </strong>Our findings suggest that TLR3 may play a role in central sensitization in CM mice by TRAF6-TAK1 axis modulating the ERK signaling pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251346373"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128263","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}
引用次数: 0
Upregulation of the neuropeptide receptor calcitonin receptor-like in the spinal cord via MLL2 in a mouse model of paclitaxel-induced peripheral neuropathy. 在紫杉醇诱导的周围神经病变小鼠模型中,通过MLL2上调脊髓神经肽受体降钙素受体样。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 DOI: 10.1177/17448069251314857
Salvador Sierra, Sara M Herz, Doan On, Mikhail G Dozmorov, M Imad Damaj, Javier Gonzalez-Maeso
{"title":"Upregulation of the neuropeptide receptor calcitonin receptor-like in the spinal cord via MLL2 in a mouse model of paclitaxel-induced peripheral neuropathy.","authors":"Salvador Sierra, Sara M Herz, Doan On, Mikhail G Dozmorov, M Imad Damaj, Javier Gonzalez-Maeso","doi":"10.1177/17448069251314857","DOIUrl":"10.1177/17448069251314857","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and severe side effect affecting cancer patients undergoing paclitaxel treatment. Growing evidence underscores the pivotal role of calcitonin-related peptide (CGRP) in the development of CIPN. Repeated administration of paclitaxel induces alterations in CGRP release from sensory neurons within the dorsal root ganglia (DRG). The density of the CGRP receptor is most prominent in the dorsal horn of the spinal cord, where it overlaps with the distribution of CGRP. However, the impact of chemotherapy treatment on expression of the CGRP receptor in the spinal cord remains unclear, as well as the potential therapeutic benefits of a CGRP receptor antagonist in an animal model of CIPN. Using a mouse model of paclitaxel-induced mechanical hypersensitivity, we show upregulation of <i>Calcitonin receptor-like receptor</i> (<i>Calcrl</i>) mRNA expression in the spinal cord, an event that occurred in association with upregulation of the H3K4 methyltransferase <i>MLL2</i>. This effect of repeated paclitaxel administration was also linked to an increase in the recruitment of MLL2, thereby enhancing levels of the active mark H3K4me2 at the <i>Calcrl</i> promoter. Furthermore, administration of the CGRP receptor antagonist BIBN4096 mitigated mechanical and cold hypersensitivity in paclitaxel-treated mice. Together, these observations suggest the CGRP receptor in the spinal cord as a potential target for reducing paclitaxel-induced neuropathic pain in animal models.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069251314857"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189938","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}
引用次数: 0
Upregulation of LRRC8A in the anterior cingulate cortex mediates chronic visceral pain in adult male mice with neonatal maternal deprivation. 表达:前扣带皮层LRRC8A的上调介导了新生儿母体剥夺成年雄性小鼠的慢性内脏疼痛。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-02-17 DOI: 10.1177/17448069251324645
Jin-Nan Lu, Jing-Heng Dou, Zi-Long Yi, Lian Lian, Xing-Lei Ben, Fu-Chao Zhang, Guang-Yin Xu
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