Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London, United Kingdom.
J Neurotrauma. 2013 Feb 1;30(3):160-72. doi: 10.1089/neu.2012.2481. Epub 2013 Jan 17.
Road traffic accidents are the most common cause of avulsion injury, in which spinal roots are torn from the spinal cord. Patients suffer from a loss of sensorimotor function, intractable spontaneous pain, and border-zone hypersensitivity. The neuropathic pains are particularly difficult to treat because the lack of a well-established animal model of avulsion injury prevents identifying the underlying mechanisms and hinders the development of efficacious drugs. This article describes a hindlimb model of avulsion injury in adult rats where the L5 dorsal and ventral spinal root are unilaterally avulsed (spinal root avulsion [SRA]), leaving the adjacent L4 spinal root intact. SRA produced a significant ipsilateral hypersensitivity to mechanical and thermal stimulation by 5 days compared with sham-operated or naïve rats. This hypersensitivity is maintained for up to 60 days. No autotomy was observed and locomotor deficits were minimal. The hypersensitivity to peripheral stimuli could be temporarily ameliorated by administration of amitriptyline and carbamazepine, drugs that are currently prescribed to avulsion patients. Histological assessment of the L4 ganglion cells revealed no significant alterations in calcitonin gene-related peptide (CGRP), IB4, transient receptor potential cation channel subfamily V member 1 (TrpV1), or N52 staining across groups. Immunohistochemistry of the spinal cord revealed a localized glial response, phagocyte infiltration, and neuronal loss within the ipsilateral avulsed segment. A comparable response from glia and phagocytes was also found in the intact L4 spinal cord, supporting the role for central mechanisms within the L4-5 spinal cord in contributing to the generation of the pain-related behavior. The SRA model provides a platform to investigate possible new pharmacological treatments for avulsion injuries.
道路交通伤害是神经根撕脱伤最常见的原因，在此过程中，脊神经根从脊髓中撕裂。患者会出现感觉运动功能丧失、难治性自发性疼痛和边缘区过敏。神经病理性疼痛尤其难以治疗，因为缺乏成熟的神经根撕脱伤动物模型，无法确定其潜在机制，也阻碍了有效药物的研发。本文描述了一种成年大鼠后肢神经根撕脱伤模型，其中 L5 背根和腹根单侧撕脱（神经根撕脱 [SRA]），而相邻的 L4 脊神经根保持完整。与假手术或未处理的大鼠相比，SRA 导致对机械和热刺激的同侧显著超敏反应，这种超敏反应可持续长达 60 天。未观察到自截行为，运动功能缺陷极小。给予阿米替林和卡马西平可暂时减轻对外周刺激的超敏反应，这两种药物目前都用于神经根撕脱伤患者。对 L4 神经节细胞的组织学评估显示，各组降钙素基因相关肽（CGRP）、IB4、瞬时受体电位阳离子通道亚家族 V 成员 1（TrpV1）或 N52 染色均无明显变化。脊髓免疫组织化学显示，在同侧撕脱段内存在局部胶质反应、吞噬细胞浸润和神经元丢失。在完整的 L4 脊髓中也发现了类似的胶质细胞和吞噬细胞反应，这支持了 L4-5 脊髓内中枢机制在产生与疼痛相关行为中的作用。SRA 模型为研究神经根撕脱伤的可能新的药物治疗方法提供了一个平台。
