慢性给予BAM8-22对吗啡镇痛作用的影响

EFFECT OF CHRONIC INTRATHECAL ADMINISTRATION OF BAM8-22 ON MORPHINE- INDUCED ANALGSIA

目的:探讨慢性激活脊髓感觉神经元特异性受体(sensory neuron-speci?c receptor,SNSR)对吗啡镇痛作用的影响。方法:雄性SD大鼠分为3组:第1组连续6 d鞘内注射生理盐水,第7天足底注射2.5%福尔马林(Formalin);第2组连续6 d鞘内注射生理盐水,第7天给吗啡(15μg)处理,再足底注射Formalin;第3组连续6 d鞘内注射SNSR特异性激动剂牛肾上腺髓8-22(Bovine adrenal medulla 8-22,BAM8-22)10 nmol,第7天先吗啡处理,再足底注射Formalin。第7天检测痛行为和脊髓背角c-Fos、NADPH的表达。结果:鞘内注射吗啡能够抑制Formalin引起的痛行为和脊髓背角c-Fos、NADPH的表达,鞘内连续6 d给予BAM8-22后,吗啡对Formalin诱发痛行为和脊髓背角c-Fos、NADPH增加的抑制作用大大减弱。结论:持续刺激SNSR,能削弱μ-阿片受体的功能。

Objective： To investigate the effects of chronic activation of SNSR （sensory-neuron specific receptors） on analgesic action of morphine. Methods： Male SD rats were divided into 3 groups. The first group received intrathecal injection of saline for 6 consecutive days followed by intraplantar injection of formalin at day 7. The second group received intrathecal injection of saline for 6 consecutive days followed by morphine （15 ~tg） treatment and then intraplantar injection of formalin at day 7. The third group received bovine adrenal medulla 8-22 （BAM8-22, the specific SNSR agonist, 10 nmol） which was administered intrathecally once per day for 6 days and received intrathecal （i.t.） injection of morphine （15 μg） followed by intraplantar injection of 2.5 % formalin at day 7. Nocifensive behaviors and the expression of c-Fos and NADPH in spinal dorsal horn were assessed at day 7. Results： Intrathecal administration of morphine inhibited formalin-induced nocifensive behaviors as well as the expression of c-Fos and NADPH in spinal dorsal horn. After daily administration of the specific SNSR agonist BAM8-22 （10 nmol） for 6 days, the i： inhibitory effect of morphine on formalin-induced behaviors and c-Fos/NADPH expressions was greatly reduced. Conclusion： Chronic activation of SNSR impaired the funional activity of μ-0igioid receptors.