The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior
The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior
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DOI：
10.1006/exnr.1999.7065
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发表时间：
1999-06-01
影响因子：
5.3
通讯作者：
DeLeo, JA
中科院分区：
文献类型：
--
作者：
Colburn, RW;Rickman, AJ;DeLeo, JA
许多大鼠周围神经病模型已经被开发来模拟人类神经病理性疼痛的情况。目前的研究试图确定周围神经损伤的部位和类型在引发机械性异位痛和脊髓神经胶质反应方面的相对重要性。大鼠在L-5脊髓水平接受7种不同的手术方法之一：脊神经冷冻神经松解术、脊神经紧密结扎、背根冷冻神经松解、背根紧密结扎、背根切断、腹根紧密结扎或椎板切除/硬膜切开假手术。分别于损伤后第1、3、5、7天测定同侧后爪机械刺激的抬足反应频率。取L-5脊髓标本进行小胶质细胞(OX-42)和星形胶质细胞(抗胶质纤维酸性蛋白)免疫组织化学分析。这两种类型的脊神经损伤，冷冻和紧密结扎，都会产生快速而严重的机械异常痛，并伴有强烈的神经胶质反应。背根损伤也导致强烈的机械性异位痛觉；然而，神经胶质反应几乎完全是星形细胞反应。腹根紧密结扎和假手术没有引起明显的行为改变，仅引起零星的神经胶质反应。背角与背根神经节的直接联系不是机械性痛觉异常发生的关键因素，因为完全损毁L-5背根神经节可引起深刻的机械敏感化。相反，小胶质细胞的激活反应似乎依赖于背根神经节介导的信号，与行为反应相反，只有当损伤发生在细胞体周围时，小胶质细胞的激活反应才是强劲的。在轴突损伤后，星形胶质细胞的激活总是可以观察到的，并可靠地与行为反应共存。(C)1999年学术出版社。
A number of rat peripheral neuropathy models have been developed to simulate human neuropathic pain conditions. The current study sought to determine the relative importance of site versus type of peripheral nerve injury in eliciting mechanical allodynia and spinal glial responses. Rats received one of seven different surgical treatments at the L-5 spinal level: spinal nerve cryoneurolysis, spinal nerve tight ligation, dorsal root cryoneurolysis, dorsal root tight ligation, dorsal root transection, ventral root tight ligation, or laminectomy/dural incision sham. Foot-lift response frequency to mechanical stimulation of the ipsilateral hindpaw was assessed postlesion on days 1, 3, 5, and 7. L-5 spinal cords were retrieved for immunohistochemical analysis of microglial (OX-42) and astrocytic (anti-glial fibrillary acidic protein) responses. Both types of spinal nerve lesion, freeze and tight ligation, produced rapid and profound mechanical allodynia with intense glial responses. Dorsal root lesions also resulted in intense mechanical allodynia; however, glial responses were almost exclusively astrocytic. Ventral root tight ligation and sham provoked no marked behavioral changes and only sporadic glial responses. Direct dorsal horn communication with the dorsal root ganglion was not a crucial factor in the development of mechanical allodynia, since decentralization of the L-5 DRG by complete L-5 dorsal root lesion produced profound mechanical sensitization. Conversely, microglial activation responses appear to be dependent upon dorsal root ganglion-mediated signals and, contrary to behavioral responses, were robust only when the lesion was made peripheral to the cell body. Astrocytic activation was always observed following axonal injury and reliably coexisted with behavioral responses. (C) 1999 Academic Press.