Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines
Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines
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DOI：
10.1016/s0304-3959(03)00138-6
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发表时间：
2003-08-01
期刊：
影响因子：
7.4
通讯作者：
DeLeo, JA
中科院分区：
文献类型：
--
作者：
Raghavendra, V;Tanga, F;DeLeo, JA
周围神经损伤常产生非生理性。持久自发性疼痛、痛觉过敏和异常性痛觉，标准治疗难治性且通常对阿片类药物（如吗啡）不敏感。最近的研究表明，在神经性疼痛的动物模型中，脊髓胶质细胞激活和促炎细胞因子增加。当这些数据放在一起考虑时。一个统一的假设出现，暗示中枢神经免疫过程在神经元和行为过敏的病因学中的作用。本研究采用实时逆转录-聚合酶链反应、RNase保护实验、酶联免疫吸附实验和免疫细胞化学方法，评估丙烯茶碱（一种神经胶质调节和抗炎剂）对大鼠L5脊髓神经横断诱导的痛觉过敏的影响以及相关的脊髓神经免疫反应增强。结果表明，慢性丙烯茶碱治疗能减轻神经性病变大鼠痛觉过敏的发生，恢复急性吗啡的镇痛活性。这些发现与丙烯茶碱抑制神经胶质细胞激活和增强脊髓促炎细胞因子的能力直接相关。这些发现以及我们早期使用相同的单神经病变动物模型观察到的丙烯茶碱的抗变动力活性支持了神经胶质和神经免疫激活调节可能是治疗或预防神经性疼痛的潜在治疗靶点的概念。此外，丙烯茶碱治疗吗啡镇痛活性的恢复表明，神经胶质活性和促炎细胞因子反应的增加可能是吗啡在神经性疼痛治疗中镇痛效果下降的原因。(C) 2003国际疼痛研究协会。Elsevier Science B.V.版权所有。
Injury to peripheral nerves often produces non-physiological. long-lasting spontaneous pain, hyperalgesia and allodynia that are refractory to standard treatment and often insensitive to opioids, such as morphine. Recent studies demonstrate spinal glial activation and increased proinflammatory cytokines in animal models of neuropathic pain. When these data are considered together. a unifying hypothesis emerges which implicates a role of central neuroimmune processes in the etiology of neuronal and behavioral hypersensitivity. The present investigation assessed the influence of propentofylline, a glial modulating and anti-inflammatory agent, on the development of L5 spinal nerve transection-induced hyperalgesia and associated enhancement of spinal neuroimmune responses using real-time reverse transcription-polymerase chain reaction, RNase protection assay, enzyme-linked immunosorbent assay, and immunocytochemistry in rats. The results show that chronic propentofylline treatment attenuated the development of hyperalgesia and restored the analgesic activity of acute morphine in neuropathic rats. These findings directly correlated with the ability of propentofylline to inhibit glial activation and enhanced spinal proinflammatory cytokines following peripheral nerve in,iffy. These findings along with our earlier observations of an anti-allodynic activity of propentofylline using the identical animal model of mononeuropathy supports the concept that modulation of glial and neuroimmune activation may be potential therapeutic targets to treat or prevent neuropathic pain. Further, restoration of the analgesic activity of morphine by propentofylline treatment suggests that increased glial activity and proinflammatory cytokine responses may account for the decreased analgesic efficacy of morphine observed in the treatment of neuropathic pain. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.