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Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 45, Issue 1, Pages: 54-62(2024)
- 作者机构：
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
- 作者简介：
WEI Xuhong；E-mail： weixhong@mail.sysu.edu.cn
- 基金信息：
DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240004.005
CLC： R338.8Published：20 January 2024，
Received：26 August 2023，
Accepted：03 December 2023
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代娟丽,王臻,董超雄等.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[J].中山大学学报（医学科学版）,2024,45(01):54-62.
DAI Juanli,WANG Zhen,DONG Chaoxiong,et al.Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(01):54-62.
代娟丽,王臻,董超雄等.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[J].中山大学学报（医学科学版）,2024,45(01):54-62. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240004.005.
DAI Juanli,WANG Zhen,DONG Chaoxiong,et al.Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(01):54-62. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240004.005.
摘要
目的
2
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
2
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
2
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-1 ß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-1 ß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
2
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。
Abstract
Objective
2
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
2
SD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level.
Results
2
SMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing 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 TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn.
Conclusion
2
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1β5-羟色胺
Keywords
chronic postoperative pain （CPSP）rostral ventromedial medulla （RVM）tumor necrosis factor alpha （TNFα）interleukin-1β （IL-1β）5-Hydroxytryptamine （5-HT）
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