Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord:: Selective actions via GalR1 and GalR2 receptors
Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord:: Selective actions via GalR1 and GalR2 receptors
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DOI：
10.1073/pnas.161293598
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发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Hökefelt, T
中科院分区：
文献类型：
--
作者：
Liu, HX;Brumovsky, P;Hökefelt, T
甘丙肽是一种由29个氨基酸组成的神经肽，在疼痛过程中具有复杂的作用。甘丙肽受体在背根神经节和脊髓中有不同的分布。在这里，我们描述了一代特定的甘丙肽R2（GalR 2）激动剂，AR-M1896，及其在大鼠神经性疼痛模型（班尼特）的研究中的应用。结果表明，在鞘内输注低剂量甘丙肽（25 ng/0.5穆尔/h）后，在正常大鼠中诱导后爪的机械性和冷异常性疼痛。用等摩尔剂量的AR-M1896或AR-M961（GalR 1和GalR 2受体的激动剂）观察到相同的效果。在异常性疼痛班尼特模型大鼠中，鞘内注射高剂量AR-M961后，机械阈值呈剂量依赖性增加，而在对照组或AR-M1896组中未观察到影响。在非异常性疼痛班尼特模型大鼠中未观察到两种化合物的作用。这些数据表明，低剂量的甘丙肽在脊髓水平具有由GalR 2受体介导的伤害性作用，而高剂量的甘丙肽对神经性疼痛的抗异常性疼痛作用是由GalR 1受体介导的。因此，选择性GalR 1激动剂可用于治疗神经性疼痛。
Galanin is a 29-aa neuropeptide with a complex role in pain processing. Several galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution. Here, we describe a generation of a specific galanin R2 (GalR2) agonist, AR-M1896, and its application in studies of a rat neuropathic pain model (Bennett). The results show that in normal rats mechanical and cold allodynia of the hindpaw are induced after intrathecal infusion of low-dose galanin (25 ng per 0.5 mul/h). The same effect is seen with equimolar doses of AR-M1896 or AR-M961, an agonist both at GalR1 and GalR2 receptors. In allodynic Bennett model rats, the mechanical threshold increased dose-dependently after intrathecal injection of a high dose of AR-M961, whereas no effect was observed in the control or AR-M1896 group. No effect of either of the two compounds was observed in nonallodynic Bennett model rats. These data indicate that a low dose of galanin has a nociceptive role at the spinal cord level mediated by GalR2 receptors, whereas the antiallodynic effect of high-dose galanin on neuropathic pain is mediated by the GalR1 receptors. Thus, a selective GalR1 agonist may be used to treat neuropathic pain.