Palazzo Enza, Fu Yu, Ji Guangchen, Maione Sabatino, Neugebauer Volker
Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
Neuropharmacology. 2008 Sep;55(4):537-45. doi: 10.1016/j.neuropharm.2008.05.007. Epub 2008 May 16.
The amygdala plays an important role in the emotional-affective component of pain and in pain modulation. Group III metabotropic glutamate receptors (mGluRs) regulate pain-related activity in the amygdala, but the behavioral consequence and contribution of individual subtypes are not known yet. This study determined the effects of mGluR7 and mGluR8 activation in the central nucleus of the amygdala (CeA) on nocifensive and affective pain responses and on pain-related anxiety-like behavior of adult rats. The pain state was induced by intraarticular injections of kaolin/carrageenan into one knee joint to produce a localized monoarthritis. Subtype-selective agonists were administered into the CeA by microdialysis in normal rats and in rats with arthritis. An mGluR7-selective agonist (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride, AMN082, 25microM) decreased spinal withdrawal reflex thresholds and increased audible and ultrasonic vocalizations evoked by brief (15s) compression of the knee. AMN082 also decreased the open-arm preference in the elevated plus maze (EPM) test, suggesting anxiety-like behavior. In arthritic animals, however, AMN082 failed to modulate the increased spinal reflexes and vocalizations and anxiety-like behavior. An mGluR8-selective agonist (S-3,4-dicarboxyphenylglycine, S-3,4-DCPG, 10microM) had no effect in normal animals but inhibited the increased spinal reflex responses and audible and ultrasonic vocalizations of arthritic rats. S-3,4-DCPG also increased the open-arm choices of arthritic rats, suggesting anxiolytic effects. The results suggest that under normal conditions mGluR7, but not mGluR8, facilitates pain responses and has anxiogenic properties whereas mGluR8, but not mGluR7, can inhibit nocifensive and affective behaviors and anxiety in a model of arthritic pain.
杏仁核在疼痛的情绪情感成分及疼痛调节中发挥着重要作用。Ⅲ型代谢型谷氨酸受体（mGluRs）调节杏仁核中与疼痛相关的活动，但单个亚型的行为后果及作用尚不清楚。本研究确定了杏仁核中央核（CeA）中mGluR7和mGluR8激活对成年大鼠伤害性和情感性疼痛反应以及与疼痛相关的焦虑样行为的影响。通过向一个膝关节内注射高岭土/角叉菜胶诱导疼痛状态，以产生局部单关节炎。在正常大鼠和患有关节炎的大鼠中，通过微透析将亚型选择性激动剂注入CeA。一种mGluR7选择性激动剂（N，N'-二苄基乙烷-1,2-二胺二盐酸盐，AMN082，25μM）降低了脊髓退缩反射阈值，并增加了短暂（15秒）压迫膝关节所诱发的可听及超声发声。AMN082还降低了高架十字迷宫（EPM）试验中的开臂偏好，提示存在焦虑样行为。然而，在患有关节炎的动物中，AMN082未能调节增强的脊髓反射和发声以及焦虑样行为。一种mGluR8选择性激动剂（S-3,4-二羧基苯基甘氨酸，S-3,4-DCPG，10μM）在正常动物中无作用，但抑制了患有关节炎大鼠增强的脊髓反射反应以及可听及超声发声。S-3,4-DCPG还增加了患有关节炎大鼠的开臂选择，提示具有抗焦虑作用。结果表明，在正常条件下，mGluR7而非mGluR8促进疼痛反应并具有致焦虑特性，而mGluR8而非mGluR7可在关节炎疼痛模型中抑制伤害性和情感性行为以及焦虑。
