Bigbee A J, Hoang T X, Havton L A
Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
Exp Neurol. 2007 Mar;204(1):273-82. doi: 10.1016/j.expneurol.2006.11.003. Epub 2006 Dec 21.
Neuropathic pain is common after traumatic injuries to the cauda equina/conus medullaris and brachial plexus. Clinically, this pain is difficult to treat and its mechanisms are not well understood. Lesions to the ventral roots are common in these injuries, but are rarely considered as potential contributors to pain. We examined whether a unilateral L6-S1 ventral root avulsion (VRA) injury in adult female rats might elicit pain within the dermatome projecting to the adjacent, uninjured L5 spinal segment. Additionally, a subset of subjects had the avulsed L6-S1 ventral roots reimplanted (VRA+Imp) into the lateral funiculus post-avulsion to determine whether this neural repair strategy elicits or ameliorates pain. Behavioral tests for mechanical allodynia and hyperalgesia were performed weekly over 7 weeks post-injury at the hindpaw plantar surface. Allodynia developed early and persisted post-VRA, whereas VRA+Imp rats exhibited allodynia only at 1 week post-operatively. Hyperalgesia was not observed at any time in any experimental group. Quantitative immunohistochemistry showed increased levels of inflammatory markers in laminae III-V and in the dorsal funiculus of the L5 spinal cord of VRA, but not VRA+Imp rats, specific to areas that receive projections from mechanoreceptive, but not nociceptive, primary afferents. These data suggest that sustained at-level neuropathic pain can develop following a pure motor lesion, whereas the pain may be ameliorated by acute root reimplantation. We believe that our findings are of translational research interest, as root implantation surgery is emerging as a potentially useful strategy for the repair of cauda equina/conus medullaris injuries.
马尾/圆锥和臂丛神经创伤性损伤后,神经病理性疼痛很常见。临床上,这种疼痛难以治疗,其机制也尚未完全了解。这些损伤中常见腹侧神经根损伤,但很少被认为是疼痛的潜在原因。我们研究了成年雌性大鼠单侧L6-S1腹侧神经根撕脱(VRA)损伤是否会在投射到相邻未损伤L5脊髓节段的皮节内引发疼痛。此外,一部分实验对象在撕脱后将撕脱的L6-S1腹侧神经根重新植入(VRA+Imp)到外侧索,以确定这种神经修复策略是否会引发或减轻疼痛。在损伤后7周内,每周对后爪足底表面进行机械性异常性疼痛和痛觉过敏的行为测试。异常性疼痛出现较早且在VRA后持续存在,而VRA+Imp大鼠仅在术后1周出现异常性疼痛。在任何实验组中,任何时候都未观察到痛觉过敏。定量免疫组织化学显示,VRA大鼠L5脊髓板层III-V和背侧索中炎症标志物水平升高,但VRA+Imp大鼠未升高,这些区域特异性地接受来自机械感受器而非伤害感受器的初级传入纤维的投射。这些数据表明,单纯的运动损伤后可能会出现持续性的同水平神经病理性疼痛,而急性神经根重新植入可能会减轻疼痛。我们认为我们的发现具有转化研究意义,因为神经根植入手术正在成为修复马尾/圆锥损伤的一种潜在有用策略。