乙酰胆碱及其M受体在吗啡成瘾大鼠蓝斑核痛觉调制的作用

ROLE OF ACETYLCHOLINE AND CHOLIVERGIC M-RECEPTOR IN PAIN MODULATION OF LOCUS CERULEUS IN MORPHINISTIC RATS

目的:研究蓝斑核(LC)在吗啡成瘾大鼠痛觉调制中的作用及其与乙酰胆碱(ACh)受体的关系。方法:采用侧脑室(icv)注射给药的方法,以电脉冲刺激坐骨神经作为伤害性痛刺激。用玻璃微电极细胞外记录方式观察LC中痛反应神经元的电活动,并观察ACh、阿托品或毛果芸香碱对吗啡成瘾大鼠LC中痛反应神经元电活动的影响。结果:(1)icv注入ACh能使吗啡成瘾大鼠LC中痛兴奋神经元(PEN)痛诱发放电频率增加、潜伏期缩短,痛抑制神经元(PIN)痛诱发放电频率减少、完全抑制时程延长;(2)icv注入ACh的M受体拮抗剂阿托品能够阻断ACh的上述效应;(3)icv注入ACh的M受体激动剂毛果芸香碱可使PEN和PIN产生与ACh作用相似的效应。结论:(1)外源性ACh或毛果芸香碱可使吗啡成瘾大鼠LC中痛反应神经元对伤害性刺激的反应增强,表现为致痛效应;(2)阿托品能使吗啡成瘾大鼠LC中痛反应神经元对伤害性刺激的反应减弱,表现为镇痛效应。上述结果提示,LC在吗啡成瘾大鼠痛觉调制中起重要作用可能是通过M受体介导而实现的。

Objective： To study the role of locus ceruleus（LC） in the algaesthesis modulation of morphinistic rats and the relationship with acetylcholine（ACh） M-receptor.Methods： The intracerebroventricular（icv） injection of drugs were used in the experiment.The sciatic nerve was stimulated by a train of electrical impulses as noxious stimulus.The electric activities of pain-related neurons in LC were recorded by the glass microelectrode.The experiment observed the effects of ACh,atropine or pilocarpine on the electric activities of the pain-excitation neurons（PEN） and pain-inhibition neurons（PIN） in LC of morphinistic rats.Results：（1） The icv injection of ACh（20μg/10μl） increased the pain-evoked discharged frequency and shortened the latency of PEN,and decreased the pain-evoked discharged frequency and prolongated of the inhibitory duration of PIN in LC of morphinistic rats.（2） The M-receptor antagonist atropine（5μg/10μl） which injected into icv could block the effect of ACh.（3） The effects of M-receptor agonist pilocarpine（5μg/10μl） on PEN and PIN were similar to the effect of ACh.Conclusions： This study suggests that the LC play a very important role in the algaesthesis modulation and the facilitatory effect of ACh on PEN or PIN response to the noxious stimulation is mediated by the M-receptors in LC.