马钱子碱通过钾离子通道调节外周镇痛

BRUCINE-INDUCED PERIPHERAL ANALGESIA DEPENDS ON POTASSIUM CHANNEL

目的:马钱子是传统的镇痛中药之一,马钱子碱(Brucine,又名布鲁生)是马钱子镇痛的有效成分,但外周镇痛机制研究较少,本文通过痛行为检测和单纤维自发放电手段,观察马钱子碱在外周损伤区中的镇痛作用机制。方法:建立慢性压迫损伤模型(chronic constriction injury, CCI),利用机械缩足反射阈值(paw withdrawal threshold, PWT)和热缩足潜伏期(paw withdrawal latency, PWL)检测大鼠的疼痛行为学变化;记录起步点单纤维自发放电检测马钱子碱对放电频率的影响。结果:与溶剂组相比,外周损伤区局部注射马钱子碱后PWT和PWL显著增加(P <0.01),预先注射非特异性钾通道阻断剂四乙基铵(Tetraethylammonium, TEA)阻断了马钱子碱的镇痛作用;马钱子碱使起步点自发放电频率显著降低(P <0.001),而灌流TEA后抑制了它的作用。结论:马钱子碱在外周具有显著地镇痛作用,并且TEA能够阻断其作用,表明钾离子通道参与马钱子碱在外周的镇痛作用。

Objective: Semen Strychni is one of the traditional Chinese medicine which serves as analgetic. It has been known that the effective component is brucine, but there were few studies on the corresponding neural mechanism of the analgesia in the peripheral nervous system. In this study, the analgesic effect of brucine in the peripheral damage area was observed through the detection of pain behaviors and the spontaneous discharge of single ?ber. Methods: Chronic Constriction Injury(CCI) model was established. Paw withdrawal threshold(PWT) and paw withdrawal latency(PWL) were used to detect the mechanical and thermal nociceptive behaviors. The effect of Brucine on spontaneous ?ring of the injured-nerve was examined. Results: PWT and P WL were increased signi?cantly after injection of brucine into peripheral injured area(P < 0.01 vs. vehicle group).Pre-injection of Tetraethylammonium(TEA), a non-speci?c potassium channel blocker blocked the analgesic effect of brucine, and brucine signi?cantly reduced the spontaneous discharge frequency in the experimental pacemaker(P < 0.001 vs. vehicle group). After TEA application, brucine administration failed to suppress ectopic activity of the injured ?bers. Conclusion: Brucine has signi?cant analgesic effect in the peripheral area, and co-administration of TEA with brucine signi?cantly reversed the analgesia and the ?ring-suppressing effect of brucine. This result indicates that potassium channel is involved in the analgesic effect of brucine in the peripheral area.