Mei Xiao-Peng, Chen Lei, Wang Wei, Wu Dan, Wang Li-Ying, Zhang Ting, Zhang Hui, Xu Li-Xian, Li Yun-Qing
Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
Neurosignals. 2013;21(3-4):184-96. doi: 10.1159/000338049. Epub 2012 Sep 7.
Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.
神经病理性疼痛是一个难治的临床问题。某些药物，如曲马多，已被证明可通过抑制伤害性神经元的活性来治疗神经病理性疼痛。此外，研究表明，抑制或调节胶质细胞激活可以预防或逆转神经病理性疼痛，例如使用小胶质细胞抑制剂米诺环素。然而，目前很少有临床治疗方法在治疗神经病理性疼痛时同时关注神经元和胶质细胞的参与。因此，本研究假设，将曲马多与作为神经元和胶质细胞激活抑制剂的米诺环素联合使用，可能对脊髓神经结扎（SNL）诱导的神经病理性疼痛产生一些协同作用。鞘内注射曲马多或米诺环素可剂量依赖性地减轻SNL诱导的机械性异常性疼痛。鞘内注射曲马多或米诺环素可下调SNL诱导的脊髓背角Fos或OX42表达。曲马多与米诺环素联合使用对SNL诱导的神经病理性疼痛也产生了强大的协同作用，且呈剂量依赖性。此外，与单独使用任何一种药物相比，药物组合增强了对SNL诱导的脊髓背角Fos和OX42表达的抑制作用。这些结果表明，曲马多与米诺环素联合使用可对周围神经损伤诱导的神经病理性疼痛产生协同作用；因此，还提出了一种通过双向打破神经元与胶质细胞之间相互作用来治疗神经病理性疼痛的新策略。
