胶质细胞和促炎性细胞因子参与鞘内注射血小板活化因子诱发的触诱发痛和热痛敏

目的:探讨脊髓胶质细胞、促炎性细胞因子TNF-α和IL-1β以及NF-κB通路在鞘内注射血小板活化因子(PAF)诱发大鼠痛敏中的作用。方法:鞘内置管成功的雄性Sprague-Dawley大鼠64只随机分为6组:人工脑脊液(artificial cerebral spinal fluid,ACSF),对照组(n=16),鞘内注射ACSF 10μl;PAF组(n=16),鞘内注射PAF 10μg,溶解于10μl人工脑脊液;二甲基亚砜(DMSO)对照组(n=8),腹腔注射0.1%DMSO生理盐水2 ml;SC-514(10 mg/kg)组Ⅰ,SC-514(50 mg/kg)组Ⅱ和SC-514(100 mg/kg)组Ⅲ(n=16)。SC-514溶解于2 ml 0.1%DMSO生理盐水。DMSO组和SC-514组在鞘内注射PAF前2 h分别腹腔注射给药。鞘内给药后测机械缩爪阈值和热缩爪潜伏期,5 h后免疫组织化学染色检测腰段脊髓GFAP和OX-42的表达,ELISA检测脊髓TNF-α和IL-1β表达。结果:鞘内注射PAF激活大鼠脊髓星形胶质细胞和小胶质细胞,GFAP和OX-42标记免疫阳性反应增强,脊髓TNF-α和IL-1β表达增强;IKKβ抑制剂SC-514剂量依赖性减轻PAF诱发的触觉痛敏和热痛敏,并抑制TNF-α和IL-1β的表达增强。结论:鞘内注射PAF诱发大鼠触诱发痛和热痛敏,脊髓胶质细胞和NF-κB通路的激活以及促炎性细胞因子TNF-α和IL-1β表达增强可能参与其机制。

THE ROLES OF GLIAL AND PROINFLAMMATORY CYTOKINES IN TACTILE ALLODYNIA AND THERMAL HYPERALGESIA INDUCED BY INTRATHECAL ADMINISTRATION OF PLATELETACTIVATING FACTOR

Objective: To investigate the roles of glial,proinflammatory cytokines and NF-κB pathway in development of tactile allodynia and thermal hyperalgesia induced by platelet-activating factor(PAF) administered intrathecally.Methods: 64 Sprague-Dawley rats with intrathecal PE-10 catheters were ran-domly divided into 6 groups: ACSF group(artificial cerebral spinal fluid,10 μl),PAF group(10 μg,dissol-ved in 10μl ACSF)group,DMSO group,SC-514(10 mg/kg)groupⅠ,SC-514(50 mg/kg)groupⅡand SC-514(100 mg/kg)groupⅢ.SC-514 were injected intraperitoneally 2 hours before intrathecal injection with PAF.Paw withdrawal mechanical threshold and thermal latency were measured after PAF administered intrathecally.The activation of astrocyte and microglia in lumbar spinal cord were assessed with immunohistochemical staining of glial fibrillary acid protein(GFAP)and OX-42 respectively.Proinflammatory cytokines TNF-αand IL-1βin lumbar spinal cord were analyzed with ELISA.Results:Intrathecally administered PAF induced tactile allodynia and thermal hyperalgesia rapidly,activated astrocyte and microglia,and increased the expressions of TNF-αand IL-1βin lumbar spinal cord.Pretreatment with SC-514 dose-dependently attenuated pain induced by PAF and inhibited the increasing of TNF-αand IL-1βexpression in spinal cord.Conclusion:Intrathecally administered PAF may induce development of tactile allodynia and thermal hyperalgesia in rats.Activation of glia and NF-κB pathway and increased expression of TNF-α and IL-1β in spinal cord may be involved in its mechanism.