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

全细胞膜片钳技术表明，选择性α_2肾上腺素受体激动剂通过脊髓α_2A和α_2C受体发挥抗伤害作用。在行为实验中，芬太尼以15分钟的间隔注射4次。随后，在芬太尼效应结束时注射吗啡。在热板试验中，戒断潜伏期未降低至基线值以下。在连续高剂量瑞芬太尼给药期间，戒断延迟也保持稳定升高。这些发现表明，急性高剂量阿片类药物治疗可能会阻止阿片类药物耐受的发展。

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.