Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia.
Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia.
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DOI：
10.1186/1744-8069-7-26
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发表时间：
2011-04-16
期刊：
影响因子：
3.3
通讯作者：
Donaldson LF
中科院分区：
文献类型：
--
作者：
Hulse RP;Wynick D;Donaldson LF
甘丙肽在背根神经节的完整感觉神经元中以低水平表达，在周围神经损伤后急剧增加。该神经肽还在背角中的初级传入末梢、脊髓中间神经元和已知调节伤害感受的许多脑区域中表达。鞘内注射甘丙肽以剂量依赖性方式调节感觉反应，在高剂量时具有抑制作用。迄今为止，尚不清楚哪种甘丙肽受体介导神经肽的抗伤害感受作用，以及它们的作用是否是外周和/或中枢介导的。在本研究中，我们研究了直接给药到甘丙肽和甘丙肽受体-2/3-激动剂Gal 2 -11的感受野的伤害性初级传入机械反应在完整的大鼠和小鼠和部分隐神经损伤（PSNI）模型的神经性疼痛的影响。外源性甘丙肽以剂量依赖性方式改变了幼稚和神经损伤动物的机械伤害性C纤维传入的反应，低浓度促进和高浓度显着抑制机械伤害性感受器活性。此外，使用甘丙肽片段Gal 2 -11证实了甘丙肽的作用是通过激活甘丙肽受体-2（GalR 2）介导的。外周GalR 2激活的抑制作用进一步得到了我们的证明的支持，即PSNI后，甘丙肽过表达转基因小鼠中的机械敏感性伤害感受器具有比野生型动物显著更高的阈值，与自发神经元放电和进入脊髓的C-纤维阻滞的显著减少相关。这些研究结果是一致的假设，即高水平的内源性甘丙肽在受伤的初级传入激活外周GalR 2，这导致C纤维机械激活阈值的增加和诱发的和正在进行的伤害性反应的显着减少。
Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain. Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord. These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.
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影响因子：
3.4
作者：
Dina, OA;Parada, CA;Levine, JD
通讯作者：
Levine, JD
影响因子：
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影响因子：
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作者：
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通讯作者：
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