Jung Chang Y, Lee Sang Y, Choi Hyo S, Lim Eun J, Lee Min K, Yang Gwi Y, Han Seung R, Youn Dong H, Ahn Dong K
Department of Oral Physiology and BrainKorea 21, School of Dentistry, Kyungpook University, Daegu, South Korea.
Neurosci Lett. 2006 Dec 6;409(3):173-8. doi: 10.1016/j.neulet.2006.09.043. Epub 2006 Oct 6.
The present study investigated the role of peripheral groups I and II metabotropic glutamate receptors (mGluRs) in interleukin (IL)-1beta-induced mechanical allodynia in the orofacial area of rats. Subcutaneous injection of 10 pg of IL-1beta decreased air-puff thresholds ipsilateral or contralateral to the injection site. The decrease in air-puff thresholds appeared 10 min after the injection of IL-1beta and IL-1beta-induced mechanical allodynia persisted for over 3 h. Pre-treatment with 7-(hydroxyimino) cyclopropa[b] chromen-1a-carboxylate ethyl ester (CPCCOEt) or 2-methyl-6-(phenylethynyl)-pyridine hydrochloride (MPEP), a mGluR1 or mGluR5 antagonist, blocked IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia produced by a subcutaneous injection of 10 pg of IL-1beta. However, post-treatment with CPCCOEt or MPEP did not affect changes in behavioral responses, which were produced by the IL-1beta injection. Pre-treatment, as well as post-treatment with (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGluR agonist, blocked either IL-1beta-induced mechanical allodynia or mirror-image mechanical allodynia. The anti-allodynic effects of APDC were abolished by pre-treatment with (2S)-2-amino-2[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), a group II mGluR antagonist. These results indicate that peripheral group II mGluRs are involved in the development and maintenance of IL-1beta-induced mechanical allodynia, while peripheral group I mGluRs are involved in the development of IL-1beta-induced mechanical allodynia. Based on our observations, the peripheral application of group II mGluR agonists may be of therapeutic value in treating inflammatory pain.
本研究调查了外周I组和II组代谢型谷氨酸受体（mGluRs）在白细胞介素（IL）-1β诱导的大鼠口面部机械性异常性疼痛中的作用。皮下注射10 pg的IL-1β可降低注射部位同侧或对侧的吹气流阈值。注射IL-1β后10分钟出现吹气流阈值降低，且IL-1β诱导的机械性异常性疼痛持续超过3小时。用mGluR1拮抗剂7-（羟基亚氨基）环丙烷[b]色烯-1a-羧酸乙酯（CPCCOEt）或mGluR5拮抗剂2-甲基-6-（苯乙炔基）-吡啶盐酸盐（MPEP）预处理可阻断IL-1β诱导的机械性异常性疼痛以及皮下注射10 pg的IL-1β所产生的镜像机械性异常性疼痛。然而，用CPCCOEt或MPEP进行后处理并不影响由IL-1β注射所产生的行为反应变化。用II组mGluR激动剂（2R,4R）-4-氨基吡咯烷-2,4-二羧酸（APDC）进行预处理以及后处理均可阻断IL-1β诱导的机械性异常性疼痛或镜像机械性异常性疼痛。用II组mGluR拮抗剂（2S）-2-氨基-2[（1S,2S）-2-羧基环丙-1-基]-3-（呫吨-9-基）丙酸（LY341495）预处理可消除APDC的抗异常性疼痛作用。这些结果表明，外周II组mGluRs参与了IL-1β诱导的机械性异常性疼痛的发生和维持，而外周I组mGluRs参与了IL-1β诱导的机械性异常性疼痛的发生。基于我们的观察结果，外周应用II组mGluR激动剂可能在治疗炎性疼痛方面具有治疗价值。
