褪黑素镇痛的相关机制

Studies on the analgesia and mechanisms of melatonin

目的 探讨褪黑素 (MT)镇痛作用与内源性阿片肽、去甲肾上腺素能神经系统及钙通道的关系。方法 大鼠和小鼠痛阈的测定采用热板法 ;β 内啡肽 (β EP)的测定采用放免法 (RIA)。结果 松果腺切除后d 8大鼠痛阈的昼夜节律性消失 ,icvMT 0 2 5mg·kg-1可出现明显的镇痛作用 ;ipMT(10 0mg·kg-1) 1h后下丘脑、垂体 β EP含量均明显降低 ;ip利血平 (3mg·kg-1)可使MT镇痛作用消失 ,而sc酚妥拉明 (10mg·kg-1)可减弱MT的镇痛作用 ;CaCl2 (2 30mg·kg-1)与MT(40mg·kg-1)合用时 ,可使MT的镇痛作用减弱 ,EGTA (180mg·kg-1)及维拉帕米 (15mg·kg-1)则可使之加强。结论 MT的镇痛作用可能与内源性阿片肽、去甲肾上腺素能神经系统及Ca2 +

AIM To study the analgesic effects of melatonin (MT) and related mechanisms. METHODS The threshold was measured by hot plate test.β endorphine (β EP) was determined by radioimmunoassay (RIA). RESULTS MT (40～160 mg·kg -1 , ip) had significant dose and time dependent analgesic effects in hot plate test. The analgesia was also induced by injection (icv) of MT (0 25 mg·kg -1 ). The day night rhythm of pain threshold was not observed in 7 d after pinealectomy, but it appeared in sham operated rats.β EP content of rat brain measured by RIA indicated that the level of β EP in hypothalamus and pituitary decreased significantly 1 h after ip MT(100 mg·kg -1 ). The analgesic effect of MT was attenuated by pretreatment of reserpine (3 mg·kg -1 ip) or α receptor blocker phentolamine (100 mg·kg -1 , sc). CaCl 2 (230 mg·kg -1 ) antagonized the analgesic effect of MT, and EGTA and verapamil significantly enhanced the analgesia of MT in the same situation. CONCLUSION MT has significant analgesic action which may be related to opiate system, adrenergic system, and Ca 2+ content.