Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain
Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain
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DOI：
10.1016/s0006-8993(00)02807-9
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发表时间：
2000-10-06
期刊：
影响因子：
2.9
通讯作者：
DeLeo, JA
中科院分区：
文献类型：
--
作者：
Arruda, JL;Sweitzer, SA;DeLeo, JA
白细胞介素-6（IL-6）是一种多效细胞因子，具有多种作用，包括调节外周和中枢神经系统。我们先前已经显示，周围神经损伤后大鼠脊髓中IL-6蛋白和信使RNA显著升高，导致提示神经病理性疼痛的疼痛行为。这些脊髓IL-6水平与神经损伤后的机械异常性疼痛强度直接相关。在目前的研究中，我们试图确定是否有可能减轻机械性异常性疼痛和/或改变脊髓神经胶质细胞激活导致周围神经损伤的特异性操纵IL-6与中和抗体或通过全局免疫调节利用免疫球蛋白（IgG）。外周施用正常山羊IgG和鞘内（i.t.）比较了IL-6中和抗体、正常山羊或正常大鼠IgG对与L5脊神经切断相关的机械性异常性疼痛的作用。在手术后第10天通过免疫组织化学评估脊髓胶质细胞活化。低剂量（0.01-0.001 μ g）目标抗大鼠IL-6 i.t.给药（P=0.025）显着减轻了异常性疼痛，并且在较高剂量下（0.08 μ g至0.008 μ g，P=0.062）趋于显着。低剂量（0.01-0.001 μ g）i.t.正常山羊和大鼠IgG显著减弱了机械性异常性疼痛，但在较高剂量下没有（0.08-0.008 μ g;对于山羊和大鼠IgG，P=0.001）。外周给予正常山羊IgG（30或100 mg/kg）没有减弱机械性异常性疼痛。脊髓神经胶质细胞活化未被任何治疗改变。这些数据提供了中枢IL-6和神经免疫调节在周围神经损伤后机械性异常性疼痛病因学中的作用的进一步证据。(C)2000 Elsevier Science B. V.保留所有权利。
Interleukin-6 (IL-6) is a pleiotrophic cytokine with a diverse range of actions including the modulation of the peripheral and central nervous system. We have previously shown significant IL-6 protein and messenger RNA elevation in rat spinal cord following peripheral nerve injury that results in pain behaviors suggestive of neuropathic pain. These spinal IL-6 levels correlated directly with the mechanical allodynia intensity following nerve injury. In the current study, we sought to determine whether it is possible to attenuate mechanical allodynia and/or alter spinal glial activation resulting from peripheral nerve injury by specific manipulation of IL-6 with neutralizing antibodies or by global immune modulation utilizing immunogamma-globulin (IgG). Effects of peripheral administration of normal goat IgG and intrathecal (i.t.) administration of IL-6 neutralizing antibody, normal goat or normal rat IgG on mechanical allodynia associated with L5 spinal nerve transection were compared. Spinal glial activation was assessed at day 10 post surgery by immunohistochemistry. Low dose (0.01-0.001 mug) goal anti-rat IL-6 i.t. administration (P=0.025) significantly decreased allodynia and trended towards significance at the higher dose (0.08 mug to 0.008 mug, P=0.062). Low doses (0.01-0.001 mug) i.t. normal goat and rat IgG significantly attenuated mechanical allodynia, but not at higher doses (0.08-0.008 mug; P=0.001 for both goat and rat IgG). Peripherally administered normal goat IgG (30 or 100 mg/kg) did not attenuate mechanical allodynia. Spinal glial activation was unaltered by any treatment. These data provide further evidence for the role of central IL-6 and neuroimmune modulation in the etiology of mechanical allodynia following peripheral nerve injury. (C) 2000 Elsevier Science B.V. All rights reserved.