Gi蛋白介导MrgC受体对CFA炎症痛的抗痛觉过敏作用

Gi Protein Mediates Anti-hyperalgesia of MrgC Receptors in CFA-inflammatory Pain

通过观察完全弗氏佐剂(complete Freund's adjuvant,CFA)炎症痛大鼠对伤害性热刺激的缩足反射潜伏期(paw withdrawal latency,PWL)变化,探讨Gi蛋白是否介导MrgC受体(Mas-related gene C receptors,MrgC)对炎症痛的抗痛觉过敏作用.结果显示,椎管内给予MrgC受体激动剂BAM8-22(bovine adrenal medulla 8-22,BAM8-22)能明显延长CFA炎症鼠在24 h和48 h时的缩足反射潜伏期基础值,并显著增强24h时的抗伤害作用.椎管内预先给予百日咳毒素(pertussis toxin,PTX)能抑制Gi蛋白的功能.在给予PTX7 d后,初次给予BAM8-22并不能延长CFA炎症鼠24 h时的缩足潜伏期基础值,但在24 h时再次注射BAM8-22时,能显著增强其抗伤害作用和48 h时的缩足潜伏期基础值.以上结果说明在CFA炎症痛模型中,预先给予PTX能抑制BAM8-22的抗痛觉过敏作用,但重复再次给予BAM8-22能恢复Gi蛋白的功能.表明Gi蛋白及其相关信号通路介导MrgC受体在炎症痛中的抗痛觉过敏作用.

The present study was designed to show if Gi protein is involved in Mas-related gene C receptors （MrgC） -produced anti-hyperalgesia in complete Freund＇s adjuvant （CFA） -inflammatory pain by measuring the paw withdrawal latency （PWL） to a noxious thermal stimulus. The results showed that intrathecal （i. t. ） administration of BAM8-22, a agonist of MrgC, markedly delayed the baseline of PWL in 24 and 48 h, and evidently grew antinociception at 24 h compared with saline group. Spinal Gi-protein function was destroyed by i.t. pretreatment with pertussis toxin （PTX）. Seven days after PFX, the first i.t. administration of BAM8-22 in CFA-inflammatory rats didn＇t delay the baseline of PWL at 24 h, but the second treatment with BAM8-22 significantly grew antinociceptive response at 24 h and prolong baseline of PWL at 48 h in PTX ＋ BAM8-22 group. The results illustrated that PTX pretreatment prevented BAM8-22-produced anti-hyperalgesia in the CFA inflammatory pain model, but repeated injection of BAM8-22 resumed the function of Gi protein. The data suggest that MrgC-produced anti-hyperalgesia is mediated by PTX-sensitive Gi proteins and the relevant signaling pathways.