{"title":"脊髓背角ERK-SGK1激活后TNF-α和乳酸水平上调是慢性术后疼痛的基础。","authors":"Yuying Li, Wenjuan Shi, Juanli Dai, Qi Jia, Gang Guo, Yanling Zhang, Weihong Zhang","doi":"10.4103/cjop.CJOP-D-22-00085","DOIUrl":null,"url":null,"abstract":"<p><p>Skin/muscle incision and retraction (SMIR) during surgeries can lead to chronic postsurgical pain (CPSP). The underlying mechanisms are still unclear. In the present study, we showed that SMIR of the thigh induced phosphorylation of extracellular signal-regulated kinase (ERK), followed by serum- and glucocorticoid-inducible kinase-1 (SGK1) activation in the spinal dorsal horn. Intrathecal injection of PD98059, an ERK inhibitor, or GSK650394, a SGK1 inhibitor, significantly attenuated mechanical pain hypersensitivity in SMIR rats. The level of tumor necrosis factor α and lactate in spinal cord was significantly decreased by PD98059 or GSK650394 injection. Furthermore, PD98059 decreased the activation of SGK1 in the spinal dorsal horn. These results indicate that ERK-SGK1 activation followed by proinflammatory mediator release in the spinal dorsal horn underlies CPSP.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Upregulated TNF-α and lactate following ERK-SGK1 activation in the spinal dorsal horn underlies chronic postsurgical pain.\",\"authors\":\"Yuying Li, Wenjuan Shi, Juanli Dai, Qi Jia, Gang Guo, Yanling Zhang, Weihong Zhang\",\"doi\":\"10.4103/cjop.CJOP-D-22-00085\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Skin/muscle incision and retraction (SMIR) during surgeries can lead to chronic postsurgical pain (CPSP). The underlying mechanisms are still unclear. In the present study, we showed that SMIR of the thigh induced phosphorylation of extracellular signal-regulated kinase (ERK), followed by serum- and glucocorticoid-inducible kinase-1 (SGK1) activation in the spinal dorsal horn. Intrathecal injection of PD98059, an ERK inhibitor, or GSK650394, a SGK1 inhibitor, significantly attenuated mechanical pain hypersensitivity in SMIR rats. The level of tumor necrosis factor α and lactate in spinal cord was significantly decreased by PD98059 or GSK650394 injection. Furthermore, PD98059 decreased the activation of SGK1 in the spinal dorsal horn. These results indicate that ERK-SGK1 activation followed by proinflammatory mediator release in the spinal dorsal horn underlies CPSP.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2023-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4103/cjop.CJOP-D-22-00085\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4103/cjop.CJOP-D-22-00085","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Upregulated TNF-α and lactate following ERK-SGK1 activation in the spinal dorsal horn underlies chronic postsurgical pain.
Skin/muscle incision and retraction (SMIR) during surgeries can lead to chronic postsurgical pain (CPSP). The underlying mechanisms are still unclear. In the present study, we showed that SMIR of the thigh induced phosphorylation of extracellular signal-regulated kinase (ERK), followed by serum- and glucocorticoid-inducible kinase-1 (SGK1) activation in the spinal dorsal horn. Intrathecal injection of PD98059, an ERK inhibitor, or GSK650394, a SGK1 inhibitor, significantly attenuated mechanical pain hypersensitivity in SMIR rats. The level of tumor necrosis factor α and lactate in spinal cord was significantly decreased by PD98059 or GSK650394 injection. Furthermore, PD98059 decreased the activation of SGK1 in the spinal dorsal horn. These results indicate that ERK-SGK1 activation followed by proinflammatory mediator release in the spinal dorsal horn underlies CPSP.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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