Molecular Pain最新文献_第5页

The involvement of spinal lncRNA RT1-CE10 in chronic functional visceral pain. 表达：脊髓lncRNA RT1-CE10参与慢性功能性内脏疼痛。

IF 2.8 3区医学

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-07-03 DOI: 10.1177/17448069251358692

Ying Tang, Zihan Liu, Xianhe Wu, Zhengqing He, Fan Yang, Huiqin Chen, Yu Chen, Qibin Zheng, Yang Huang, Aiqin Chen, Chun Lin

{"title":"The involvement of spinal lncRNA RT1-CE10 in chronic functional visceral pain.","authors":"Ying Tang, Zihan Liu, Xianhe Wu, Zhengqing He, Fan Yang, Huiqin Chen, Yu Chen, Qibin Zheng, Yang Huang, Aiqin Chen, Chun Lin","doi":"10.1177/17448069251358692","DOIUrl":"10.1177/17448069251358692","url":null,"abstract":"Irritable bowel syndrome (IBS) is characterized by chronic visceral pain, but its molecular mechanisms remain controversial, hindering effective treatment. This research is to investigate the role of lncRNA RT1-CE10 in chronic visceral pain associated with IBS and to elucidate the underlying molecular mechanisms. An IBS rat model was developed in rats, and RNA-Seq analysis was conducted to assess lncRNA RT1-CE10 expression. The subcellular localization of lncRNA RT1-CE10 and its co-localization with ATP1a3 in spinal cord neurons were examined. AAV was used to over-express lncRNA RT1-CE10 in the spinal cord to study its effects on ATP1a3 levels and pain response, with knockdown experiments to evaluate the impact of reduced lncRNA RT1-CE10. The RNA-Seq analysis revealed a significant down-regulation of lncRNA RT1-CE10 in IBS rats. The lncRNA was found to be expressed in both the cytoplasm and the nucleus and to co-localize with ATP1a3 in spinal cord neurons. Over- expression of lncRNA RT1-CE10 via AAV-lncRT1-CE10 increased ATP1a3 levels and alleviated visceral pain response, while knockdown of lncRNA RT1-CE10 decreased ATP1a3 levels and enhanced visceral pain response. Additionally, a marked decrease in ATP1a3 expression was observed in the spinal cords of IBS rats. Modulating ATP1a3 expression either through over-expression or knockdown could alleviate or aggravate chronic visceral pain, respectively. LncRNA RT1-CE10, which is lowly expressed in the spinal cord of IBS rats, interacts with ATP1a3 and influences chronic visceral pain. These findings could lead to the development of targeted therapeutic interventions for IBS.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251358692"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560570","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

Seeking the root causes of menstrual pain: A systematic review of biomarkers in menstrual effluent. EXPRESS：寻找月经疼痛的根本原因：月经流出物生物标志物的系统综述。

IF 2.8 3区医学

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-07-05 DOI: 10.1177/17448069251360092

Chandrashekara N Kyathanahalli, Frank F Tu, Gabriela Ashenafi, Margaret S Schroer, Kevin M Hellman

{"title":"Seeking the root causes of menstrual pain: A systematic review of biomarkers in menstrual effluent.","authors":"Chandrashekara N Kyathanahalli, Frank F Tu, Gabriela Ashenafi, Margaret S Schroer, Kevin M Hellman","doi":"10.1177/17448069251360092","DOIUrl":"10.1177/17448069251360092","url":null,"abstract":"Dysmenorrhea (period pain) affects over 40% of women and is a leading cause of missed school and workdays. However, the molecular mechanisms underlying this pain are not fully understood. We conducted a systematic review (Prospero registration: CRD42024535081) to identify and evaluate the biomolecules in menstrual effluent that may contribute to dysmenorrhea and assess how non-hormonal medications (e.g. NSAIDs) impact these biomarkers. Fifteen studies involving two hundred twenty-three participants met the inclusion criteria. We used the Newcastle-Ottawa Scale (for observational studies) and the Cochrane RoB2 tool (for randomized controlled trials) to evaluate the risk of bias and the quality of studies. Eight studies consistently reported elevated prostaglandin levels in the menstrual effluent of women with dysmenorrhea, though sample sizes were generally small, and methodological issues were noted. Seven studies demonstrated that NSAIDs reduce prostaglandin concentrations; however, these trials utilized multiple-day dosing protocols instead of single-dose regimens, leaving questions about acute treatment effects. Two studies highlighted alternative molecular targets, such as 12-HETE and platelet-activating factor (PAF), that may also play key roles in menstrual pain. Overall, elevated prostaglandins are a recurring finding, but the limited scope and design of existing studies indicate a need for larger, methodologically rigorous investigations. Nevertheless, the few studies that identified molecules other than prostaglandins suggest there are viable druggable targets for clinical trials to reduce menstrual pain.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251360092"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567555","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

Inhibition of mTOR/S6K1/Gli1 signaling alleviates morphine-induced thermal hyperalgesia and tolerance. 抑制mTOR/S6K1/Gli1信号可减轻吗啡诱导的热痛觉过敏和耐受性。

IF 2.8 3区医学

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-08-26 DOI: 10.1177/17448069251376198

Xing-He Wang, Long Wang, Long Yang, Yang Bai, Ling-Fei Xu, Miao-Miao Li, Yu-Cheng Liu, Jia Sun, Su Liu

{"title":"Inhibition of mTOR/S6K1/Gli1 signaling alleviates morphine-induced thermal hyperalgesia and tolerance.","authors":"Xing-He Wang, Long Wang, Long Yang, Yang Bai, Ling-Fei Xu, Miao-Miao Li, Yu-Cheng Liu, Jia Sun, Su Liu","doi":"10.1177/17448069251376198","DOIUrl":"10.1177/17448069251376198","url":null,"abstract":"Aims: The precise mechanisms underlying the pathogenesis of opioid-induced thermal hyperalgesia and tolerance are not yet fully understood.Methods: In adult CD-1 mice, repeated morphine treatment was used to examine the expression of the non-canonical pathway of sonic hedgehog signaling, behavioral changes, and neurochemical alterations induced by morphine in the spinal cord and DRG. Additionally, to delve into the underlying mechanisms of the non-canonical pathway of Shh signaling in morphine-induced thermal hyperalgesia (MITH) and tolerance, we utilize the brain-derived neurotrophic factor (BDNF) inhibitor.Results: Morphine administration repeatedly resulted in apparent thermal hyperalgesia and tolerance. The initiation and maintenance of MITH and tolerance, as well as related neurochemical alterations, were greatly inhibited by pharmacological and genetic suppression of the mTOR. By blocking the mTOR/p70 ribosomal S6 protein kinase 1 (S6K1)/Gli1 signaling, the morphine-induced increase in BDNF was considerably inhibited. Moreover, mTOR activator injection in naive mice resulted in significant heat hyperalgesia and BDNF upregulation. Suppression of BDNF effectively mitigated the development of thermal hyperalgesia induced by the mTOR activator.Conclusion: These findings indicate that the non-canonical pathway of Shh signaling might serve as a crucial mediator in the development of MITH and tolerance through the regulation of BDNF expression.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069251376198"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086568","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":"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.","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":"Background: 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).Methods: 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).Results: 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.Conclusions: Our findings suggest that TLR3 may play a role in central sensitization in CM mice by TRAF6-TAK1 axis modulating the ERK signaling pathway.","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

Utidelone induces mechanical and cold allodynia in mice via TRPA1 activation. EXPRESS：优替龙通过激活TRPA1诱导小鼠机械和冷性异常痛。

IF 2.8 3区医学

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-08-28 DOI: 10.1177/17448069251377633

Wenwen Gao, Cunjin Su, Liya Dai, Jialong Tao, Yusong Zhang

{"title":"Utidelone induces mechanical and cold allodynia in mice via TRPA1 activation.","authors":"Wenwen Gao, Cunjin Su, Liya Dai, Jialong Tao, Yusong Zhang","doi":"10.1177/17448069251377633","DOIUrl":"10.1177/17448069251377633","url":null,"abstract":"Objective: Utidelone (UTD1), a recently approved epothilones analog in China for metastatic breast cancer, is endorsed in combination with capecitabine for metastatic breast cancer patients who have encountered first-line therapy failures. Despite its clinically verified therapeutic efficacy, it is concurrently associated with peripheral neuropathic pain, particularly affecting extremities. However, the etiology of UTD1-induced peripheral neuropathic pain remains unclear.Methods: The present investigation built a mouse pain model induced by UTD1, resulting in marked mechanical and cold allodynia.Results: Examination of the dorsal root ganglia unveiled a notable upregulation of TRPA1, accompanied by noteworthy alterations in oxidative stress-related markers, including ATF4, SOD2, CAT, and Cyt-C. The TRPA1 antagonist HC-030031, resulted in the alleviation of mechanical and cold allodynia in the UTD1-induced pain model, as well as two antioxidants, including Mito-tempo and edaravone.Interpretation: The present study will provide new strategies for pain relieving induced by UTD1.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251377633"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962170","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":"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 Calcitonin receptor-like receptor (Calcrl) mRNA expression in the spinal cord, an event that occurred in association with upregulation of the H3K4 methyltransferase MLL2. 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 Calcrl 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.","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

Calcium channels in anesthesia management: A molecular and clinical review. 钙通道在麻醉管理中的应用：分子和临床综述。

IF 2.8 3区医学

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-05-10 DOI: 10.1177/17448069251343417

Mostafa Saberian, Afzal Shamsi, Mahdieh Mehrab Mohseni, Ashkan Taghizadehimani, Elham Shahidi Delshad

{"title":"Calcium channels in anesthesia management: A molecular and clinical review.","authors":"Mostafa Saberian, Afzal Shamsi, Mahdieh Mehrab Mohseni, Ashkan Taghizadehimani, Elham Shahidi Delshad","doi":"10.1177/17448069251343417","DOIUrl":"10.1177/17448069251343417","url":null,"abstract":"Calcium channels play an essential role in the molecular and physiological mechanisms underlying anesthesia by mediating intracellular calcium ion (Ca2+) flux, which regulates key processes such as neurotransmitter release, neuronal excitability, and immune responses. Voltage-gated calcium channels (VGCCs) and ligand-gated calcium channels (LGCCs) are integral to the anesthetic process, with subtypes such as T-type VGCCs and NMDA receptors influencing consciousness and pain perception. This review emphasizes current evidence to highlight how anesthetic agents interact with calcium channels via direct inhibition and modulation of intracellular signaling pathways, such as phosphatidylinositol metabolism. Additionally, calcium channelopathies - genetic or acquired dysfunctions affecting VGCCs and LGCCs - pose challenges in anesthetic management, including arrhythmias, malignant hyperthermia, and altered anesthetic sensitivity. These findings underscore the critical need for precision medicine approaches tailored to patients with these conditions. While significant progress has been made in understanding the roles of calcium channels in anesthesia, knowledge gaps remain regarding the long-term implications of anesthetic interactions on calcium signaling and clinical outcomes. This review bridges foundational science with clinical practice, emphasizing the translational potential of calcium channel research for optimizing anesthetic strategies. By integrating molecular insights with emerging pharmacogenomic approaches, it provides a pathway for developing safer and more effective anesthesia protocols that enhance patient outcomes.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251343417"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973050","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

{"title":"Upregulation of LRRC8A in the anterior cingulate cortex mediates chronic visceral pain in adult male mice with neonatal maternal deprivation.","authors":"Jin-Nan Lu, Jing-Heng Dou, Zi-Long Yi, Lian Lian, Xing-Lei Ben, Fu-Chao Zhang, Guang-Yin Xu","doi":"10.1177/17448069251324645","DOIUrl":"10.1177/17448069251324645","url":null,"abstract":"Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder primarily characterized by chronic visceral pain. Studies have reported that the anterior cingulate cortex (ACC) is involved in chronic visceral pain, however, the molecular mechanisms underlying this involvement remain largely unclear. In this study, we aimed to investigate the molecular mechanisms of the ACC in chronic visceral pain induced by neonatal maternal deprivation (NMD) in male mice. We showed that the expression of leucine-rich repeat-containing protein family member 8A (LRRC8A) at both mRNA and protein levels was significantly upregulated in the ACC of NMD male mice, with LRRC8A primarily co-localized in neurons. DCPIB, an inhibitor of LRRC8A, greatly alleviated chronic visceral pain. Moreover, the ATP concentration was significantly upregulated in the ACC of NMD male mice. However, LRRC8A was not involved in somatic pain induced by complete Freund's adjuvant (CFA) injection into the hind paw. In conclusion, our findings demonstrate that LRRC8A plays a critical role in regulating chronic visceral pain in NMD mice. These findings are expected to provide new ideas for the treatment of chronic visceral pain in IBS patients.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251324645"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440958","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

RIPK3 regulates microglial polarization through the TLR4/MyD88 pathway in neuropathic pain. EXPRESS: RIPK3在神经性疼痛中通过TLR4/MyD88通路调控小胶质细胞极化。

IF 2.8 3区医学

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-08-30 DOI: 10.1177/17448069251377861

Sihan E, Qingbiao Song, Zhaokun Zhang, Yingxia Liang

{"title":"RIPK3 regulates microglial polarization through the TLR4/MyD88 pathway in neuropathic pain.","authors":"Sihan E, Qingbiao Song, Zhaokun Zhang, Yingxia Liang","doi":"10.1177/17448069251377861","DOIUrl":"10.1177/17448069251377861","url":null,"abstract":"Peripheral nerve injury activates microglia in the spinal, promoting microglial polarization and facilitating neuropathic pain progression. Necroptosis, a form of cell death, plays a crucial role in various neurological diseases and receptor-interacting protein kinases 3(RIPK3) a key molecular in the process. This study investigates to explore that RIPK3 regulates microglial polarization through the TLR4/MyD88 signaling pathway in neuropathic pain. By using a chronic constriction injury (CCI) model in mice, we found that peripheral nerve injury promoted M1 polarization and activated the TLR4/MyD88 pathway in spinal cord; in BV-2 microglia models, TNF-α/Z-VAD co-induction triggered M1 polarization through TLR4/MyD88 pathway, TLR4 antagonists suppressed these effects both in vivo and in vitro. Administration of GSK'872 (RIPK3 inhibitor) inhibited TLR4/MyD88 pathway, reduced microglial M1 polarization, promoted microglial M2 polarization and alleviated CCI-induced hyperalgesia. These findings suggest that necroptosis is a key cellular mechanism in peripheral injury-induced neuropathic pain and that RIPK3 regulates microglial polarization via the TLR4/MyD88 pathway, providing a new target for neuropathic pain treatment and clinical prevention.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251377861"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962164","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