家兔中脑导水管周围灰质中注射八肽胆囊收缩素(CCK-8)拮抗吗啡镇痛和电针镇痛  

ANTAGONISM OF MORPHINE ANALGESIA AND ELECTROACUPUNCTURE ANALGESIA BY CHOLECYSTOKININ OCTAPEPTIDE (CCK-8) ADMINISTERED IN PERIAQUEDUCTAL GRAY(PAG) OF THE RABBITS

作　　者：曹威[1] 周仲福[1] 韩济生[1] 

机构地区：[1]北京医科大学生理教研室

出　　处：《生理学报》1989年第4期388-394,共7页Acta Physiologica Sinica

基　　金：国家自然科学基金;NIDA grant资助项目

摘　　要：家兔单侧PAG内注射CCK-83ng,能使静脉注射4mg/kg吗啡引起的镇痛作用降低73％或使电针镇痛效果降低67％。在1.5—6.0ng范围内呈量效关系。无硫的CCK-8无此作用。PAG内注射CCK受体拮抗剂proglumide 4μg可翻转CCK-8的抗吗啡镇痛作用。说明PAG部位注射外源性CCK-8可通过CCK受体对抗阿片镇痛。 PAG内注射CCK-8抗血清可显著增强静脉注射2mg/kg吗啡的镇痛效果。PAG内注射CCK抗血清本身也能引起痛阈轻度升高。说明PAG内有内源性的CCK-8发挥紧张性的抗阿片镇痛作用。We have reported that intracerebroventricular (i. c. v.) injection of 1—4 ng of CCK-8 to the (?)at produced a remarkable antagonistic effect on morphine analgesia. In order to study the species specificity and the site of action, CCK-8 was microinjected into the PAG of the rabbit, and its influence on morphine analgesia and electroacupuncture analgesia was observed.The latency of the escape responce (ERL) to radiant heat focused on the snout was measured as an index of the pain threshold. Microinjections were made via cannulae chronically implanted into the PAG. The drug solutions were delivered in a volume of 1 μl, at a speed of 0.125μl / min. The ERL was measured for a period of 60 or 70 minutes at 10 min intervals.1. CCK-8 administered unilaterally to the PAG of the rabbit at a dose of 3 ng antagonized the analgesia induced by morphine (4mg / kg, i. v. ) by 73％ (P<0.001), and reduced the analgesic effect of electroacupuncture by 67％ (P<0.001). These effects were dose-dependent within the range from 1.5 ng to 6.0 ng. The effect of CCK-8 was reversed by CCK receptor blocker proglumide (4 μl, intra-PAG injection). Unsulfated CCK-8 (CCK-us) had no effect in this regard. These results indicate that in the PAG of the rabbit, exogenously administered CCK8 was capable of antagonizing opioid analgesia by the activation of CCK receptors.2. Two groups of rabbits were given with morphine (2mg/kg, i. v.) and simultaneous injection of CCK-8 antiserum (CCK-AS, 1 μl) or normal rabbit serum (NRS) into the PAG. While in the NRS control group there was an increase in ERL of only 16％, the CCK-AS group showed an increase of 68％ (P<0.001), indicating a dramatic potentiation of morphine analgesia. Administration of 1 μl of NRS or CCK-AS into the PAG caused an increase in ERL of 10％ and 25％ respectively, indicating that CCK-AS per se had a mild analgesic effect. The results suggest a tonic release of endogenous CCK-8 in the PAG to antagonize opioid analgesia.

关 键 词：CCK-8 止痛 吗啡 电针 

分 类 号：R338.3[医药卫生—人体生理学]