外周炎症性疼痛刺激诱发中枢神经系统小胶质细胞增殖活化

Spinal Microglial Reactions Induced by Peripheral Inflammatory Pain Stimulation

目的 观察外周疼痛刺激后 ,中枢神经系统小胶质细胞形态和功能特征的变化。方法 采用福尔马林疼痛动物模型 ,刺激后 2、4、8h,1、3 d,1、2及 4周后处死 ,制成腰脊髓和脑干切片。小胶质细胞特异表达补体 C3受体(单克隆抗体 OX-4 2 ) ,活化型小胶质细胞表达 类主要组织相容性复合物 Ia(单克隆抗体 OX-6)。定性和定量的免疫组化方法显示中枢小胶质细胞及疼痛刺激下形态的转化。结果 福尔马林刺激侧腰脊髓后角和脑干薄束核内小胶质细胞的增殖活化 ,注射后 1 d开始出现 ,3 d后明显 ,1周达到高峰 ,2周后增殖活化反应开始消退。本研究增殖活化的小胶质细胞表现为激活型 ,而非活化型或吞噬型。结论 福尔马林注射引起的疼痛刺激或外周炎症反应可能诱发中枢小胶质细胞增殖活化。

Objective This study was designed to investigate the response of microglia in the lumbar spinal cord and in the brainstem to a tonic noxious stimulus.Methods Thirty two male Sprague Dawley rats received subcutaneous injections of 5% formalin (50 μL) into the plantar surface of the right hindpaw, and twenty four rats were injected with 50 μL saline as a control. The lumbar spinal cord and brainstem were evaluated for immunoreactivity (IR) to complement receptor C3bi (monoclonal antibody OX 42) and major histocompatibility complex class Ⅱ(monoclonal antibody OX 6) on post injection hours 0, 2, 4, 8 and days 1, 3, 7, 14, and 28.Results A qualitative and quantitative increase of OX 42 IR microglial cells were observed in the medial portion of the dorsal horn and in the gracile nucleus of the brainstem on the side ipsilateral to the formalin injection, starting on day 1 3 and peaking at day 7 post injection. OX 6 positive cells were scattered both in gray and white matter, but no difference was detected between the two sides of the spinal cord or between formalin injected and control animals.Conclusions This is the first study that reports that subcutaneous injection offormalin into the rat's hind paw induces microglial activation in the spinal cord as well as in the brainstem.Although we have not determined whether these responses result from nociceptor activity, peripheral inflammation, or degeneration of primary afferents and/or central neurons, this method provides a simple, effective and stable animal model that will permit the future study of the mechanisms that contribute to microglial activation and its pathophysiological consequences.