Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal nitric oxide synthase in the dorsal root ganglion and cuneate nucleus
Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal nitric oxide synthase in the dorsal root ganglion and cuneate nucleus
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DOI：
10.1016/j.pbb.2013.03.002
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发表时间：
2013-05-01
影响因子：
3.6
通讯作者：
Lue, June-Horng
中科院分区：
文献类型：
--
作者：
Wang, Hsin-Ying;Tsai, Yi-Ju;Lue, June-Horng
在这项研究中，我们通过使用一氧化氮合酶 (NOS) 抑制剂和 NO 供体研究了一氧化氮 (NO) 在溶血磷脂酰胆碱 (LPC) 诱导的周围神经病变中的作用。我们发现 LPC 治疗正中神经会诱发神经性疼痛行为（异常性疼痛和痛觉过敏）和神经脱髓鞘。免疫组织化学显示，背根神经节 (DRG) 和楔状核 (CN) 中神经元 NOS 样免疫反应 (nNOS-LI) 神经元的数量增加，并在 LPC 治疗后 1 周达到峰值。对 LPC 处理的神经进行电刺激后，注射 LPC 后同侧 CN 中的 c-Fos-LI 神经元数量也以剂量依赖性方式增加，并在 1 周时达到峰值。注射 4% LPC 1 周后给予 L-NAME（N-omega-硝基-L-精氨酸甲酯）或 7-NI（7-硝基吲唑）可减轻触觉异常性疼痛和热痛觉过敏。然而，NO供体S-亚硝基-N-乙酰青霉胺（SNAP）的应用只会加剧热痛觉过敏。对 LPC 处理的正中神经进行电刺激后，L-NAME 和 7-NI 组 CN 中 c-Fos-LI 神经元的数量减少，但 SNAP 组增加。综上所述，我们的研究结果表明，在 LPC 治疗后，DRG 和 CN 中 nNOS 数量急剧增加所产生的高级 NO 可能与神经病理性感觉有关，并增强了 CN 中的神经元活动。 (C) 2013 Elsevier Inc. 保留所有权利。
In this study, we investigated the role of nitric oxide (NO) in lysophosphatidylcholine (LPC) induced peripheral neuropathy by the use of nitric oxide synthase (NOS) inhibitors and NO donor. We found that LPC treatment of the median nerve induced neuropathic pain behaviors (allodynia and hyperalgesia) and nerve demyelination. Immunohistochemistry revealed that the amounts of neuronal NOS-like immunoreative (nNOS-LI) neurons in both the dorsal root ganglion (DRG) and cuneate nucleus (CN) increased and peaked at 1 week after LPC treatment. Following electrical stimulation of the LPC-treated nerve, the number of c-Fos-LI neurons in the ipsilateral CN also increased in a dose-dependent manner following LPC injection and peaked at 1 week. Administration of L-NAME (N-omega-Nitro-L-arginine methyl ester) or 7-NI (7-nitroindazole) 1 week after 4% LPC injection attenuated tactile allodynia and thermal hyperalgesia. However, the application of the NO donor S-Nitroso-N-acetylpenicillamine (SNAP) only exacerbated thermal hyperalgesia. After electrical stimulation of the LPC-treated median nerve, the number of c-Fos-LI neurons in the CN diminished in the L-NAME and 7-NI groups, but increased in the SNAP group. Taken together, our findings suggest that advanced NO made by the dramatically increased number of nNOS in the DRG and CN might be involved in the neuropathic sensation and boosted neuronal activity in the CN after LPC treatment. (C) 2013 Elsevier Inc. All rights reserved.