Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states
Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states
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DOI：
10.1016/j.neuroscience.2008.03.084
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发表时间：
2008-06-23
期刊：
影响因子：
3.3
通讯作者：
Carlton, S. M.
中科院分区：
文献类型：
--
作者：
Du, J.;Zhou, S.;Carlton, S. M.
几条证据表明，II组代谢型谷氨酸受体（mGluR）的激活可以抑制感觉传递。我们已经报道了大鼠指神经中无髓鞘轴突上II组mGluR的表达，其中许多被认为是伤害感受器[Carlton SM，Hargett GL，科格斯霍尔RE（2001 b）大鼠初级传入轴突上代谢型谷氨酸受体2/3的定位。Neuroscience 105：957-969]。本研究的目的是进一步理解外周伤害感受器处理的II组调节，使用炎症模型记录行为变化，并首次记录暴露于II组激动剂（2 R，4 R）-4-氨基吡咯烷-2，4-二羧酸酯（APDC）和拮抗剂（2S）-2-氨基-2-[（1 S，2S）-2-羧基环丙-1-基]-3-（咕吨-9-基）丙酸（LY 341495，LY）。这些数据表明，外周II组mGluR激活不会抑制非致敏状态下（即短暂的伤害性机械或热刺激后）的伤害性行为或伤害性感受器纤维反应，但当伤害性感受器因暴露于福尔马林或炎症汤而致敏时，可以抑制这些反应。II组mGluR激动剂诱导的抑制可被选择性II组拮抗剂阻断。在这些研究中诱发的外周II组mGluR诱导的抑制通过激活局部受体而不是通过脊髓或脊髓上机制发生。数据表明，选择性II组激动剂的管理可能是有效的治疗剂，用于预防外周致敏和治疗炎性疼痛。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Several lines of evidence indicate that Group II metabotropic glutamate receptor (mGluR) activation can depress sensory transmission. We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve [Carlton SM, Hargett GL, Coggeshall RE (2001b) Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in the rat. Neuroscience 105:957-969]. The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist (2S)-2-amino-2-[(1 S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495, LY). The data indicate that peripheral Group II mGluR activation does not depress nociceptive behaviors or nociceptor fiber responses in the nonsensitized state (i.e. following brief nociceptive mechanical or thermal stimulation) but can depress these responses when nociceptors are sensitized by exposure to formalin or inflammatory soup. Group II mGluR agonist-induced inhibition can be blocked by a selective Group II antagonist. Peripheral Group II mGluR-induced inhibition evoked in these studies occurs through activation of local receptors and not through spinal or supraspinal mechanisms. The data indicate that administration of selective Group II agonists may be potent therapeutic agents for prevention of peripheral sensitization and for treatment of inflammatory pain. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.