Analgesic effects ofα2-adrenoceptor agonist in morphine-tolerant rats.

利用全细胞膜片钳技术发现，选择性α2-肾上腺素受体激动剂通过α 2a和α 2c -肾上腺素受体在脊髓中发挥抗感觉作用。行为实验中，芬太尼注射4次，每隔15分钟注射一次。随后，芬太尼作用结束时注射吗啡。在热板试验中，戒断潜伏期没有低于基线值。在持续大剂量瑞芬太尼给药期间，停药潜伏期也稳定升高。这些发现表明，急性大剂量阿片类药物治疗可能会阻止阿片类药物耐受性的发展。

It was revealed using whole-cell patch-clamp technique that a selectiveα2-adrenoceptor agonist contributed to its antinociceptive action throughα2A-andα2C-adrenoceptors in the spinal cord. In behavioral experiments, fentanyl was injected 4 times at 15-min intervals. Subsequently, morphine was injected at the end of the fentanyl effects. Withdrawal latencies did not decrease below baseline values in the hot plate test. Withdrawal latencies also remained steadily elevated during continuous high-dose remifentanil administration. These findings suggest that acute high-dose opioid treatment might prevent the development of opioid tolerance.