采用缩足反射观察椎管内注射感觉神经元特异性受体(SNSR)激动剂牛肾上腺髓质8-22肽(BAM8-22)对吗啡耐受的影响.结果表明.椎管内注射BAM8-22(O.1nm01)后,吗啡抗伤害作用的半数有效剂量由耐受时的80.99pg恢复至12.38pg(P〈0.001);隔天混合给予BAM8-22后.能显著延缓吗啡耐受,第6天吗啡抗伤害作用的半数有效剂量为14.84μg,与吗啡耐受组相比有极显著差异(P〈0.001);但这两组动物吗啡的抗伤害作用没有达到正常吗啡组水平(P〈0.05和P〈0.01).连续椎管内单独注射BAM8-226d后,吗啡抗伤害作用的半数有效剂量为12.23μg,明显高于正常吗啡组(P〈0.01).但又明显低于吗啡耐受组(P〈0.001).而椎管内连续6d混合给予BAM8-22和吗啡,并不能阻止吗啡耐受.研究表明,椎管内注射BAM8-22能部分翻转或延缓吗啡的耐受,而BAM8-22的长期作用则会部分降低吗啡的抗伤害作用,提示感觉神经元特异性受体参与了阿片受体功能的调制。
To investigate the effect of intrathecal (i. t.) administration of bovine adrenalmedulla 8-22 (BAM8-22), an agonist of sensory neuron-specific receptors (SNSR), on mor- phine tolerance by paw withdrawal test. It was found that i.t. administration of BAM8-22(0. 1 nmol) evidently reversed established morphine tolerance, half effective dose of mor- phine antinociception reduced from 80.99μg in morphine tolerance to 12.38μg Mter BAMS-22 reversed (P 〈 0. 001) . Co-administration of BAM8-22 (0. 1 nmol) every other day, but not daily, with morphine remarkably attenuated the development of morphine tolerance, halfeffective dose of morphine antinociception in sixth day was 14.84 μg (P〈0. 001) . But antinociception of these two groups didn't reach to morphine in naive group level (P〈0.05and P〈0. 01) . Half effective dose of morphine antinociception was 12.23 μg after i.t. ad- ministration of BAM8-22 (0. 1 nmol) daily for six days, it was significantly higher than mor-phine in naive group (P ,(0.05) , but evidently lower than morphine tolerant group (P〈0. 001) . Co-administration of BAMS-22 daily, with morphine didn't attenuate the develop-ment of morphine to lerance. The present study showed that BAM8-22 inhibited the develop-ment and expression of tolerance to morphine, while chronic BAM8-22 weakened antinoci- ceptive response of morphine. These results suggest that SNSR is involved in the modulation of opioid receptors function.