Galanin-Mediated Behavioural Hyperalgesia from the Dorsomedial Nucleus of the Hypothalamus Involves Two Independent Descending Pronociceptive Pathways
Galanin-Mediated Behavioural Hyperalgesia from the Dorsomedial Nucleus of the Hypothalamus Involves Two Independent Descending Pronociceptive Pathways
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DOI：
10.1371/journal.pone.0142919
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发表时间：
2015-11-13
期刊：
影响因子：
3.7
通讯作者：
Pinto-Ribeiro, Filipa
中科院分区：
文献类型：
--
作者：
Amorim, Diana;Viisanen, Hanna;Pinto-Ribeiro, Filipa
甘丙肽（GAL）激活下丘脑背内侧核（DMH）诱导行为痛觉过敏。由于DMH神经元不直接投射到脊髓，我们推测，延髓背侧网状核（DRt），一个投射到脊髓背角（SDH）的原伤害性区域和/或作用于脊髓5-HT 3受体（5 HT（3）R）的多巴胺能中缝-脊髓通路可以中继GAL在DMH中诱导的下行伤害性易化。在单关节炎（阿尔斯）和对照（SHAM）动物中，对DMH、DRt和脊髓进行药理学操作后，评估了热诱发的缩爪潜伏期（PWL）和SDH神经元的活性。结果表明，GAL的DMH和谷氨酸的DRt导致行为痛觉过敏的SHAM和阿尔斯动物，这是特别伴随着增加的热诱发反应的宽动态范围神经元，一组伤害性SDH神经元。GAL在DMH中诱导的疼痛行为易化作用在DRt中被利多卡因逆转，在脊髓中被5 HT（3）R拮抗剂昂丹司琼逆转。然而，脊髓恩丹西酮不能阻断谷氨酸在DRt引起的痛敏。此外，在阿尔斯而不是假手术动物中，在DRt中的利多卡因和脊髓中的昂丹司琼后PWL增加。我们的数据表明，GAL在DMH激活两个独立的下行易化通路：（i）一个继电器在DRt和（ii）另一个涉及5-HT神经元作用于脊髓5 HT（3）Rs。在实验性阿尔斯中，这两条下行通路的强直性疼痛易化作用都有所增加。
Activation of the dorsomedial nucleus of the hypothalamus (DMH) by galanin (GAL) induces behavioural hyperalgesia. Since DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt), a pronociceptive region projecting to the spinal dorsal horn (SDH) and/or the serotoninergic raphe-spinal pathway acting on the spinal 5-HT3 receptor (5HT(3)R) could relay descending nociceptive facilitation induced by GAL in the DMH. Heat-evoked paw-withdrawal latency (PWL) and activity of SDH neurones were assessed in monoarthritic (ARTH) and control (SHAM) animals after pharmacological manipulations of the DMH, DRt and spinal cord. The results showed that GAL in the DMH and glutamate in the DRt lead to behavioural hyperalgesia in both SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of pain behaviour induced by GAL in the DMH was reversed by lidocaine in the DRt and by ondansetron, a 5HT(3)R antagonist, in the spinal cord. However, the hyperalgesia induced by glutamate in the DRt was not blocked by spinal ondansetron. In addition, in ARTH but not SHAM animals PWL was increased after lidocaine in the DRt and ondansetron in the spinal cord. Our data demonstrate that GAL in the DMH activates two independent descending facilitatory pathways: (i) one relays in the DRt and (ii) the other one involves 5-HT neurones acting on spinal 5HT(3)Rs. In experimental ARTH, the tonic pain-facilitatory action is increased in both of these descending pathways.