Department of Physiology, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
Neurosci Lett. 2011 Aug 18;500(3):197-201. doi: 10.1016/j.neulet.2011.06.035. Epub 2011 Jun 29.
Group 1 metabotropic glutamate receptors (mGluRs) are expressed in peripheral and central neural tissues and involved in peripheral and central sensitization in various pain models. However, there are limited reports that activation of peripheral group I mGluRs could evoke pain. Furthermore, any behavioral evidences could not be found out, showing what kind of afferent fibers are involved in peripheral mGluRs-mediated hyperalgesia. This study was undertaken to clarify whether peripherally injected group I mGluRs agonists could induce pain-related behaviors and capsaicin-sensitive afferent fibers might be involved in the hyperalgesia. To assess pain sensitivity, mechanical threshold for paw withdrawal response (PWT) was measured and number of spontaneous flinching behavior was counted. Intraplantar injection of group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG) and mGluR5 agonist, (RS)-2-chloro-5-hydroxyphenyglycine (CHPG) immediately induced pain-like behaviors, such as decrease of PWT and increased number of flinchings. These agonists-induced pain-like behaviors were blocked by group I mGluRs antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) and mGluR5 antagonist, 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). Perineural pretreatment of 1% capsaicin solution significantly reduced pain-related behaviors induced by DHPG and CHPG, proposing that capsaicin-sensitive primary afferent fibers could be responsible for the hyperalgesia induced by activation of peripheral group I mGluRs. This study presents the first behavioral evidence that peripheral group I mGluRs activation could induce spontaneous as well as mechanical hyperalgesia and capsaicin-sensitive afferent fiber could be implicated the group I mGluR mediated hyperalgesia.
第一组代谢型谷氨酸受体（mGluRs）在周围和中枢神经系统组织中表达，并参与各种疼痛模型中的外周和中枢敏化。然而，仅有有限的报道表明激活外周第一组 mGluRs 可以引起疼痛。此外，没有发现任何行为证据表明哪种传入纤维参与外周 mGluRs 介导的痛觉过敏。本研究旨在阐明外周注射第一组 mGluRs 激动剂是否会引起与疼痛相关的行为，以及辣椒素敏感的传入纤维是否参与痛觉过敏。为了评估疼痛敏感性，测量了足底退缩反应（PWT）的机械阈值，并计算了自发性抽搐行为的次数。第一组 mGluR 激动剂（RS）-3,5-二羟基苯甘氨酸（DHPG）和 mGluR5 激动剂（RS）-2-氯-5-羟基苯甘氨酸（CHPG）的皮内注射立即引起类似疼痛的行为，如 PWT 降低和抽搐次数增加。这些激动剂引起的类似疼痛的行为被第一组 mGluRs 拮抗剂（RS）-1-氨基茚烷-1,5-二羧酸（AIDA）和 mGluR5 拮抗剂 2-甲基-6-（苯乙炔基）吡啶盐酸盐（MPEP）阻断。1%辣椒素溶液的周围神经预处理显著减少了由 DHPG 和 CHPG 引起的与疼痛相关的行为，这表明辣椒素敏感的初级传入纤维可能负责由激活外周第一组 mGluRs 引起的痛觉过敏。本研究首次提供了行为学证据，表明外周第一组 mGluRs 的激活可引起自发性和机械性痛觉过敏，并且辣椒素敏感的传入纤维可能参与第一组 mGluR 介导的痛觉过敏。
