Carlton Susan M, Du Junhui, Zhou Shengtai
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1069, USA.
Brain Res. 2009 Jan 12;1248:86-95. doi: 10.1016/j.brainres.2008.10.066. Epub 2008 Nov 7.
Transient receptor potential vanilloid 1 (TRPV1) receptors are critical to nociceptive processing. Understanding how these receptors are modulated gives insight to potential therapies for pain. We demonstrate using double labeling immunohistochemistry that Group II metabotropic glutamate receptors (mGluRs) are co-expressed with TRPV1 on rat dorsal root ganglion (DRG) cells. In behavioral studies, intraplantar 0.1 microM APDC, a group II agonist, significantly attenuates capsaicin-induced nociceptive behaviors through a local effect. The APDC-induced inhibition of capsaicin responses is blocked by 1 microM LY341495, a group II antagonist. At the single fiber level, nociceptor responses to capsaicin are significantly decreased following exposure to APDC and this effect is blocked by LY341495. Finally, activation of peripheral group II mGluRs inhibits forskolin-induced thermal hyperalgesia and nociceptor heat sensitization, suggesting group II receptors are negatively coupled to the cAMP/PKA pathway. The data indicate that group II mGluRs and TRPV1 receptors are co-expressed on peripheral nociceptors and activation of mGluRs can inhibit painful sensory transmission following TRPV1 activation. The data are consistent with group II and TRPV1 receptors being linked intracellularly by the cAMP/PKA pathway. Peripheral group II mGluRs are important targets for drug discovery in controlling TRPV1-induced nociception.
瞬时受体电位香草酸亚型1（TRPV1）受体对伤害性信息处理至关重要。了解这些受体如何被调节有助于深入了解疼痛的潜在治疗方法。我们使用双重标记免疫组织化学证明，II型代谢型谷氨酸受体（mGluRs）与TRPV1在大鼠背根神经节（DRG）细胞上共表达。在行为学研究中，足底注射0.1微摩尔APDC（一种II型激动剂）通过局部作用显著减轻辣椒素诱导的伤害性行为。APDC诱导的对辣椒素反应的抑制被1微摩尔LY341495（一种II型拮抗剂）阻断。在单纤维水平，伤害感受器对辣椒素的反应在暴露于APDC后显著降低，且这种作用被LY341495阻断。最后，外周II型mGluRs的激活抑制了福斯高林诱导的热痛觉过敏和伤害感受器热敏感化，表明II型受体与cAMP/PKA途径负性偶联。数据表明，II型mGluRs和TRPV1受体在外周伤害感受器上共表达，且mGluRs的激活可在TRPV1激活后抑制疼痛感觉传递。这些数据与II型和TRPV1受体通过cAMP/PKA途径在细胞内相连一致。外周II型mGluRs是控制TRPV1诱导的伤害感受的药物研发的重要靶点。
