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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
WEI Xuhong;E-mail: weixhong@mail.sysu.edu.cn
Published: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.
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。
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.
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
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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