{"title":"n -去甲基青藤碱主要通过调节α2亚型GABAA受体缓解雄性小鼠神经性疼痛。","authors":"Weiwei Rong, Xunjia Qian, Yujian Yin, Yipeng Gu, Weiyi Su, Jie-Jia Li, Yue Xu, Hongyan Zhu, Junxu Li, Qing Zhu","doi":"10.1111/cns.70197","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p><i>N</i>-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We examined the analgesic effects of NDSM using both pain-evoked and pain-suppressed behavioral assays in two persistent pain models. Then western blot assay and immunofluorescence staining were used to investigate the effects of NDSM on the expression of the GABA<sub>A</sub> receptor α2 subunit (GABRA2) and inflammatory factors in the spinal cord and brain tissues of male spared nerve injury (SNI) mice. Finally, the individual subtypes of GABA<sub>A</sub>Rs (α1, α2, α3, and α5) were respectively silenced by viral-mediated knockdown to explore the involvement of subtypes of GABA<sub>A</sub>Rs in the effects of NDSM on the pain-like behaviors in male SNI mice.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>NDSM demonstrated significant analgesic effects against chronic pain both in pain-evoked and pain-suppressed behavioral assays. NDSM treatment significantly reversed the SNI induced down-regulation of GABRA2 and up-regulation of TNF-α and IL-1β. The analgesic effects of NDSM were completely blocked by silencing GABRA2 or partially blocked by silencing GABRA3.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This study provided the first evidence that the analgesic effects of NDSM are mediated primarily by GABRA2 and partially by GABRA3, and the inhibition of neuroinflammation also contributes to the analgesic effects of NDSM.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696256/pdf/","citationCount":"0","resultStr":"{\"title\":\"N-Demethylsinomenine Relieves Neuropathic Pain in Male Mice Mainly via Regulating α2-Subtype GABAA Receptors\",\"authors\":\"Weiwei Rong, Xunjia Qian, Yujian Yin, Yipeng Gu, Weiyi Su, Jie-Jia Li, Yue Xu, Hongyan Zhu, Junxu Li, Qing Zhu\",\"doi\":\"10.1111/cns.70197\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p><i>N</i>-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We examined the analgesic effects of NDSM using both pain-evoked and pain-suppressed behavioral assays in two persistent pain models. Then western blot assay and immunofluorescence staining were used to investigate the effects of NDSM on the expression of the GABA<sub>A</sub> receptor α2 subunit (GABRA2) and inflammatory factors in the spinal cord and brain tissues of male spared nerve injury (SNI) mice. Finally, the individual subtypes of GABA<sub>A</sub>Rs (α1, α2, α3, and α5) were respectively silenced by viral-mediated knockdown to explore the involvement of subtypes of GABA<sub>A</sub>Rs in the effects of NDSM on the pain-like behaviors in male SNI mice.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>NDSM demonstrated significant analgesic effects against chronic pain both in pain-evoked and pain-suppressed behavioral assays. NDSM treatment significantly reversed the SNI induced down-regulation of GABRA2 and up-regulation of TNF-α and IL-1β. The analgesic effects of NDSM were completely blocked by silencing GABRA2 or partially blocked by silencing GABRA3.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>This study provided the first evidence that the analgesic effects of NDSM are mediated primarily by GABRA2 and partially by GABRA3, and the inhibition of neuroinflammation also contributes to the analgesic effects of NDSM.</p>\\n </section>\\n </div>\",\"PeriodicalId\":154,\"journal\":{\"name\":\"CNS Neuroscience & Therapeutics\",\"volume\":\"31 1\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-01-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696256/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS Neuroscience & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cns.70197\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70197","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
N-Demethylsinomenine Relieves Neuropathic Pain in Male Mice Mainly via Regulating α2-Subtype GABAA Receptors
Aims
N-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.
Methods
We examined the analgesic effects of NDSM using both pain-evoked and pain-suppressed behavioral assays in two persistent pain models. Then western blot assay and immunofluorescence staining were used to investigate the effects of NDSM on the expression of the GABAA receptor α2 subunit (GABRA2) and inflammatory factors in the spinal cord and brain tissues of male spared nerve injury (SNI) mice. Finally, the individual subtypes of GABAARs (α1, α2, α3, and α5) were respectively silenced by viral-mediated knockdown to explore the involvement of subtypes of GABAARs in the effects of NDSM on the pain-like behaviors in male SNI mice.
Results
NDSM demonstrated significant analgesic effects against chronic pain both in pain-evoked and pain-suppressed behavioral assays. NDSM treatment significantly reversed the SNI induced down-regulation of GABRA2 and up-regulation of TNF-α and IL-1β. The analgesic effects of NDSM were completely blocked by silencing GABRA2 or partially blocked by silencing GABRA3.
Conclusion
This study provided the first evidence that the analgesic effects of NDSM are mediated primarily by GABRA2 and partially by GABRA3, and the inhibition of neuroinflammation also contributes to the analgesic effects of NDSM.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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