RVM致炎细胞因子上调导致5-HT释放参与调控慢性术后疼痛  

Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release

作　　者：代娟丽 王臻 董超雄 李玉莹 魏绪红[3] DAI Juanli;WANG Zhen;DONG Chaoxiong;LI Yuying;WEI Xuhong(Xiehe Shenzhen Hospital,Huazhong University of Science and Technology,Shenzhen 518052,China;ShenzhenPolytechnic University,Shenzhen 518055,China;Department of Physiology,Zhongshan School of Medicine//Department of Physiology and Pain Research Center,Sun Yat-Sen University,Guangzhou 510080,China)

机构地区：[1]华中科技大学协和深圳医院,广东深圳518052 [2]深圳职业技术大学,广东深圳518055 [3]中山大学中山医学院生理教研室,疼痛研究中心,广东广州510080

出　　处：《中山大学学报（医学科学版）》2024年第1期54-62,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81870969,81471250);广东省自然科学基金(2019A1515011855);深圳市南山区科技计划项目(NS2021078);深圳职业技术大学校级项目(6023310001K)。

摘　　要：【目的】探讨延髓头端腹内侧部(RVM)内致炎细胞因子肿瘤坏死因子α(TNFα)和白介素-1β(IL-1β)释放增多导致5-羟色胺(5-HT)向脊髓释放增多在慢性术后疼痛(CPSP)模型中的作用。【方法】按照随机方式将SD大鼠进行如下分组:对照组、皮肤/肌肉切开和牵拉(SMIR)(1d,7d)组、SMIR+RVM内注射TNFα或IL-1β中和性抗体组、SMIR+RVM内注射TNFα或IL-1β组、SMIR+RVM内注射溶剂组,用up-down方法测量大鼠50%机械刺激撤足阈值,免疫组化检测RVM内TNFα或IL-1β表达情况,酶联免疫吸附测定法(ELISA)方法观察RVM及脊髓背角内5-HT含量的变化。【结果】SMIR可引起大鼠机械痛敏,表现为50%机械刺激撤足阈值下降,持续至少3周。SMIR后,RVM内神经元和星形胶质细胞中的TNFα和IL-1β表达上调。TNFα或IL-1β中和抗体(每天一次行SMIR术前30 min给予,共4次))微量注射入RVM可阻断SMIR引起的50%机械刺激撤足阈值下降,并可降低RVM及脊髓背角5-HT的含量。正常动物RVM内注射TNFα和IL-1β也可导致50%机械刺激撤足阈值下降,且引起RVM及脊髓内5-HT含量增加。【结论】RVM中致炎细胞因子增多可能通过引起5-HT释放增多参与调控SMIR后慢性术后疼痛的发生发展。【Objective】To investigate the role of proinflammatory cytokines tumor necrosis factor alpha(TNFα)and interleukin-1β(IL-1β)in rostral ventromedial medulla(RVM)in chronic postsurgical pain(CPSP)induced by skin/muscle incision and retraction(SMIR).【Methods】SD rats were randomly divided into 5 groups:①Sham group;②SMIR group;③SMIR+TNFα/IL-1βneutralizing antibody group;④SMIR+TNFα/IL-1βgroup and⑤SMIR+vehicle group.50%paw mechanical withdrawal threshold(MWT)was measured by the up-down method,immunofluroscence was used to detect the TNFαand IL-1βexpression and ELISA for the 5-Hydroxytryptamine(5-HT)level.【Results】SMIR elicited persistent nociceptive sensitization,upregulated TNFαand IL-1βexpression in RVM neurons and astrocytes.Microinjection of TNFαor IL-1βneutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn.While microinjection of recombinant TNFαor IL-1βinto RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn.【Conclusion】Up-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

关 键 词：慢性术后痛 延髓头端腹内侧部 肿瘤坏死因子α 白介素1Β 5-羟色胺 

分 类 号：R338.8[医药卫生—人体生理学]