Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain
Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain
复制标题
曲马多和丙茶碱联合给药对大鼠脊髓神经结扎引起的神经性疼痛具有协同作用
DOI：
10.1371/journal.pone.0072943
复制
发表时间：
2013-08-29
期刊：
影响因子：
3.7
通讯作者：
Mei, Xiao-Peng
中科院分区：
文献类型：
--
作者：
Zhang, Jin;Wu, Dan;Mei, Xiao-Peng
神经病理性疼痛是一个棘手的临床问题。据报道，药物治疗如曲马多通过抑制伤害性神经元的活性来有效地减少神经性疼痛。还已经报道，调节神经胶质活化也可以通过施用神经胶质调节剂或抑制剂（例如丙戊茶碱）来预防或逆转神经性疼痛。到目前为止，还没有结合神经元和神经胶质参与治疗神经性疼痛的临床策略。因此，本研究旨在评估曲马多和丙戊茶碱分别作为神经元和胶质细胞活化抑制剂联合给药是否会对减少大鼠脊神经结扎（SNL）诱导的神经病理性疼痛产生协同作用。大鼠接受SNL手术以诱导神经病理性疼痛。进行疼痛行为测试以确定药物对SNL诱导的具有von-Frey毛发的机械异常性疼痛的影响。Real-time RT-PCR检测促炎因子白细胞介素-1 β（IL-1β）的表达。鞘内曲马多和丙戊茶碱单独给药以剂量依赖性方式缓解SNL诱导的机械性异常性疼痛。曲马多和丙戊茶碱联合给药比单独鞘内给药产生更有效的协同作用和剂量依赖性。Real-time RT-PCR结果显示，损伤后同侧脊髓背角IL-1β表达上调，曲马多和丙戊茶碱联合用药可显著降低损伤后同侧脊髓背角IL-1β的表达。抑制促炎因子IL-1β参与了曲马多和丙戊茶碱联合用药对大鼠周围神经损伤性神经病理性疼痛的协同作用。因此，我们的研究提供了一个合理的利用一个新的策略，通过阻断中枢神经系统中的促炎因子相关的途径来治疗神经性疼痛。
Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.