背根神经节嘌呤受体亚型P2X3R介导小鼠术后急—慢痛转化

Dorsal root ganglion receptor subtype P2X3R mediates postoperative-hyperalgesic priming in mice

目的探讨不同部位不同嘌呤受体亚型在小鼠切口术后痛转化中的作用差异。方法足底切口恢复后注射PGE_(2)构建术后痛转化模型。第一部分:C57BL/6小鼠随机分为对照(Con)组、假敏化(sHP)组、敏化(HP)组,检测机械痛阈、自发痛评分和焦虑样行为;Western blot检测患侧L 3-5背根神经节(DRG)和脊髓背角(SCDH)中P2X3R和P2X7R蛋白表达变化。第二部分:C57BL/6小鼠随机分为Con组、HP+生理盐水组、HP+P2X3R拮抗剂组或HP+P2X7R拮抗剂组,观察拮抗不同亚型嘌呤受体对小鼠机械痛阈的影响。结果与正常小鼠相比,切口痛小鼠注射PGE_(2)后机械痛阈明显下降,自发痛评分明显增加(P<0.05),未表现出焦虑样行为(P>0.05),且P2X3R蛋白在DRG中表达明显增多(P<0.05),在SCDH中未检出,而P2X7R蛋白在DRG和SCDH各组中表达均无差异(P>0.05)。拮抗P2X3R能阻断术后痛转化的产生,而拮抗P2X7R无明显影响。结论切口痛小鼠经PGE_(2)诱导可出现急慢性痛的转化,不伴发焦虑样情绪,DRG中P2X3R可能是参与术后痛转化的关键受体之一。

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice.Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE_(2) after plantar incision recovery.Part I:C57BL/6 mice were randomly divided into control(Con),sham hyperalgesic priming(sHP)and hyperalgesic priming(HP)groups to detect mechanical pain thresholds,spontaneous pain scores and anxiety-like behaviours;Western blot was performed to detect the changes in P2X3R and P2X7R protein expression in the affected L3-5 dorsal root ganglion(DRG)and spinal cord dorsal horn(SCDH).Part II:C57BL/6 mice were randomly divided into Con group,HP+saline group,HP+P2X3R antagonist group or HP+P2X7R antagonist group to observe the effect of antagonizing different subtypes of purinergic receptors on mechanical pain threshold in mice.Results Compared with normal mice,incision pain mice injected with PGE_(2) showed a significant decrease in mechanical pain threshold and a marked increase in spontaneous pain score(P<0.05),and did not show anxiety-like behaviour(P>0.05).Antagonizing P2X3R blocked the production of postoperative-hyperalgesic priming,while antagonizing P2X7R had no significant effect.Conclusion P2X3R in DRG may be one of the key receptors involved in postoperative-hyperalgesic priming.