β-制动蛋白2在炎性痛小鼠脊髓背角的表达及作用

Expression and role ofβ-arrestin2 in spinal dorsal horn of mice with inflammatory pain

目的:通过建立不同类型的炎性痛模型,观察β-制动蛋白2(Arrb2)在炎性痛小鼠疼痛发展过程中的作用。方法:在WT小鼠和Arrb2^(-/-)小鼠建立由卡拉胶(carrageenan)诱导急性炎性痛模型和弗氏完全佐剂(CFA)诱导慢性炎性痛模型,通过von Frey纤维丝法测定不同时间点的机械缩足反应阈值(PWT);利用Western Blot技术观察Arrb2在急性痛和慢性痛中的表达;在脊髓背角采用鞘内给药的方式,通过von Frey纤维丝法检测小鼠给予μ受体选择性激动剂(DAMGO)后短期和长期的PWT。结果:与WT小鼠相比,Arrb2^(-/-)小鼠在急性痛状态下痛敏恢复程度较慢,而在慢性痛早期表现出显著的抑痛作用。Western Blot结果显示:在急性痛模型下,脊髓背角Arrb2蛋白表达无明显变化,而在慢性痛模型下,Arrb2蛋白表达下降。最后,鞘内注射DAMGO实验表明,在急性痛模型下,敲除Arrb2后鞘内注射DAMGO短期无显著作用,后期可诱发吗啡耐受样痛敏;在慢性痛状态下,敲除Arrb2后鞘内注射DAMGO则在短期和长期均表现出镇痛作用的显著增强。结论:Arrb2在不同类型的炎性痛中表达和作用均有所不同。

Objective:To investigate the role ofβ-arrestin2(Arrb2)in the development of inflammatory pain in mice by establishing different types of inflammatory pain models.Methods:Carrageenan induced acute inflammatory pain model and Freund's complete adjuvant(CFA)induced chronic inflammatory pain model were established in WT and Arrb2-/-mice,the paw withdrawal mechanical threshold(PWT)was measured at different time points by von Frey filament method.Western Blot was used to observe the expression of Arrb2 in acute pain and chronic pain.The von Frey filament method was used to detect the short-term and long-term PWT of mice after intrathecal administration ofμreceptor selective agonist(DAMGO).Results:In Arrb2 knockout mice,the recovery of acute hyperalgesia was slower than that of the mice without Arrb2 knockout,but the Arrb2 knockout mice showed significant analgesic effect at the early stage of chronic pain.Western Blot results showed that the expression of Arrb2 in spinal dorsal horn decreased in chronic pain model.There was no significant change in expression after acute pain.Finally,in the acute pain model,the knockout of Arrb2 induced morphine toleration-like hyperalgesia after intrathecal injection of DAMGO,which had no significant effect in the short-term.In the chronic pain state,intrathecal injection of DAMGO after Arrb2 knockout significantly enhanced the analgesic effect in both short and long term.Conclusion:Arrb2 plays different roles in different types of inflammatory pain.