Initial Phase of Neuropathic Pain within a Few Hours after Nerve Injury in Mice
Initial Phase of Neuropathic Pain within a Few Hours after Nerve Injury in Mice
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DOI：
10.1523/jneurosci.6753-10.2011
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发表时间：
2011-03-30
影响因子：
5.3
通讯作者：
Shibuki, Katsuei
中科院分区：
文献类型：
--
作者：
Komagata, Seiji;Chen, Shanlin;Shibuki, Katsuei
我们测试了一个假设，即神经损伤后几小时内诱导的脊柱可塑性可能会导致皮质活动的变化和神经性疼痛的初始阶段。通过小鼠经颅黄素蛋白荧光成像观察振动刺激引起的体感皮质反应。切断感觉神经后，这些反应立即减弱。然而，由附近神经介导的剩余皮质反应在神经切断后几个小时内得到增强。神经损伤会引起神经性疼痛。在本研究中，小鼠在神经损伤后1-2周表现出触觉异常性疼痛。同侧背柱的损伤，介导触觉皮质反应，消除了对触觉刺激的躯体皮质反应。然而，在神经损伤后的几个小时内，针对相同的触觉刺激出现了非触觉皮质反应，表明触觉异常性疼痛是急剧引发的。我们研究了皮质变化背后的触发机制。迈斯纳小体中发现的内源性胶质细胞系衍生的神经营养因子（GDNF）在其 Aβ 触觉传入中诱导类似于 0.1 Hz 或更低的基底放电，并且基底放电的破坏触发了非触觉皮层反应的增强。将 10nM LY341495[(2S)-2-amino-2-[(1S, 2S)-2-carboxycyclopropl-yl]-3-(xanth-9-yl)propanoic Acid]（II 类代谢型谷氨酸受体 (mGluRs) 的特异性拮抗剂）应用于脊髓表面也可诱导非触觉皮质反应的增强。总之，这表明 GDNF 在触觉敏感神经纤维中产生的低频传入放电持续激活脊髓 II 组 mGluR，并且这种激活失败会引发触觉异常性疼痛。
We tested a hypothesis that the spinal plasticity induced within a few hours after nerve injury may produce changes in cortical activities and an initial phase of neuropathic pain. Somatosensory cortical responses elicited by vibratory stimulation were visualized by transcranial flavoprotein fluorescence imaging in mice. These responses were reduced immediately after cutting the sensory nerves. However, the remaining cortical responses mediated by nearby nerves were potentiated within a few hours after nerve cutting. Nerve injury induces neuropathic pain. In the present study, mice exhibited tactile allodynia 1-2 weeks after nerve injury. Lesioning of the ipsilateral dorsal column, mediating tactile cortical responses, abolished somatic cortical responses to tactile stimuli. However, nontactile cortical responses appeared in response to the same tactile stimuli within a few hours after nerve injury, indicating that tactile allodynia was acutely initiated. We investigated the trigger mechanisms underlying the cortical changes. Endogenous glial cell line-derived neurotrophic factor ( GDNF), found in the Meissner corpuscles, induced basal firing similar to 0.1 Hz or less in its A beta tactile afferents, and disruption of the basal firing triggered the potentiation of nontactile cortical responses. Application of 10nM LY341495[(2S)-2-amino-2-[(1S, 2S)-2-carboxycyclopropl-yl]-3-(xanth-9-yl)propanoic acid], a specific antagonist of group II metabotropic glutamate receptors (mGluRs), on to the surface of the spinal cord also induced the potentiation of nontactile cortical responses. Together, it is suggested that low-frequency afferent firing produced by GDNF in touch-sensitive nerve fibers continuously activated spinal group II mGluRs and that failure of this activation triggered tactile allodynia.