TNFα 参与了核苷逆转录酶抑制剂诱导的大鼠神经病理性疼痛。
TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats.
机构信息
Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
出版信息
Brain Behav Immun. 2011 Nov;25(8):1668-76. doi: 10.1016/j.bbi.2011.06.010. Epub 2011 Jun 28.
Abstract
In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTIs). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2',3'-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain.
摘要
在 HIV/AIDS 患者中，神经病理性疼痛是一种常见的神经系统并发症。HIV 感染本身可能导致神经病理性疼痛，而当患者接受核苷逆转录酶抑制剂 (NRTIs) 治疗时，疼痛症状会加重。NRTIs 导致神经病理性疼痛的机制尚不清楚。在目前的研究中，我们测试了 TNFα 在抗逆转录病毒药物诱导的神经病理性疼痛中的作用。我们给小鼠系统地给予 2',3'-双脱氧胞苷 (ddC，一种 NRTI) 以诱导机械性痛觉过敏。我们发现 ddC 诱导脊髓背角中 GFAP 和 TNFα 的 mRNA 和蛋白表达过度。TNFα 在脊髓背角与 GFAP 共定位，在 DRG 与 NeuN 共定位。用 siRNA 敲低 TNFα 可阻断 ddC 诱导的机械性痛觉过敏。鞘内给予胶质抑制剂或重组 TNF 可溶性受体可逆转 ddC 诱导的机械性痛觉过敏。这些结果表明 TNFα 参与了 NRTI 诱导的神经病理性疼痛。
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