Marabese I, de Novellis V, Palazzo E, Scafuro M A, Vita D, Rossi F, Maione S
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery-Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
Neuropharmacology. 2007 Feb;52(2):253-62. doi: 10.1016/j.neuropharm.2006.04.006. Epub 2006 Nov 17.
In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.
在本研究中,已在炎症性和神经性疼痛模型中研究了选择性代谢型谷氨酸受体8(mGlu8)激动剂(S)-3,4-二羧基苯基甘氨酸(DCPG)的作用,以阐明mGlu8受体在调节痛觉中的作用。清醒小鼠经外周注射福尔马林或角叉菜胶诱导炎症性疼痛。在福尔马林注射前15分钟进行(S)-3,4-DCPG的全身给药,可降低福尔马林试验的早期和延迟伤害性反应。当在福尔马林外周注射后15分钟进行此治疗时,仍可减轻后期痛觉过敏阶段。同样,在角叉菜胶注射前15分钟给予全身(S)-3,4-DCPG可减轻角叉菜胶诱导的热痛觉过敏和机械性异常性疼痛,但在角叉菜胶诱导的炎症性疼痛发展后给予(S)-3,4-DCPG时,未观察到对疼痛行为的影响。当微量注射到外侧导水管周围灰质(PAG)时,III组受体拮抗剂(RS)-α-甲基丝氨酸-O-磷酸酯(MSOP)可拮抗全身给予(S)-3,4-DCPG在两种炎症性疼痛模型中诱导的镇痛作用。在福尔马林或角叉菜胶注射前10分钟给予外侧PAG内(S)-3,4-DCPG可减轻疼痛行为;两种作用均被外侧PAG内MSOP阻断。坐骨神经慢性压迫损伤7天后,(S)-3,4-DCPG在减轻热痛觉过敏和机械性异常性疼痛方面无效,而在手术后3天证明有效。综上所述,这些结果表明,刺激mGlu8受体可减轻炎症性疼痛中福尔马林和角叉菜胶诱导的痛觉过敏,而在已建立的炎症性或神经性疼痛中似乎效果较差。