蛋白激酶A在老年大鼠腹壁切口疝术中应用瑞芬太尼诱发的痛觉过敏中的作用机制

摘要

Objective The objective of this research was to investigate that proteinkinase A (PKA) may contribute to remifentanil-induced hyperalgesia (RIH) as the downstream of ephrinB/EphB signaling.Methods Aged male SD rats were made into abdominal wall hernia model.A week later,they were abdominal hernia repaired under remifentanil compound sevoflurane anesthesia.We characterized the remifentanil-induced pain behaviours by evaluating thermal hyperalgesia and mechanical allodynia in a rat hind paw.Protein expression of PKA in spinal cord was assayed by western blotting.Results Continuing infusion of remifentanil produced a thermal hyperalgesia and mechanical allodynia,which was accompanied with increased expression of spinal PKA protein,what appeared above was inhibited by pretreatment with EphB2-Fc,an antagonist of ephrinB/EphB.H89,inhibitors of PKA,suppressed pain behaviours induced by remifentanil infusion and reversed the increased pain behaviours induced by intrathecal injection of ephrinB2-Fc,an agonist of ephrinB/EphB.Conclusions Our findings confirmed that PKA is involved in remifentanil-induced hyperalgesia related to ephrinB/EphB signaling.EphrinB/EphB signaling might be the upstream of PKA.This study provides fundamental theory for novel intervention targets for treatment of remifentanil-induedhyperalgesia.%目的 探讨蛋白激酶A (PKA)是否可作为ephrinB/EphB信号通路下游的效应分子,进而介导ephrinB/EphB信号相关的痛觉过敏(remifentanil-induced hyperalgesia,RIH)发生发展过程.方法 以老年雄性SD大鼠进行腹壁切口疝造模,在瑞芬太尼复合七氟烷麻醉下行腹壁切口疝修补术.我们检测大鼠的机械痛觉异常和热痛觉过敏以及PKA蛋白水平,以评价行腹壁切口疝修补术大鼠术中应用瑞芬太尼麻醉引起的术后痛觉过敏.结果 阻滞EphB、PKA活性抑制了瑞芬太尼诱发的机械性和热痛觉过敏,阻滞EphB受体抑制脊髓PKA的活化,阻滞PKA活性抑制了ephrinB/EphB激活引起的痛觉过敏.结论 实验证明PKA作为ephrirB/EphB信号系统的下游作用位点在瑞芬太尼诱导的痛觉过敏过程中发挥调制作用.本研究为临床上寻找治疗RIH的新靶点提供理论依据.