间隔联合应用BAM8-22增强慢性吗啡抑制c-Fos表达的作用

Intermittent Co-administration of BAM8-22 Enhances the Inhibition of Chronic Morphine on Formalin-evoked c-Fos Expression

通过观察腰段脊髓背角c-Fos阳性神经元数量变化,探讨鞘内间隔联合应用牛肾上腺髓质8-22肽（bovine adrenal medulla 8-22,BAM8-22）在福尔马林引起的持续性痛中对吗啡耐受的影响.结果显示,连续6 d应用吗啡导致耐受（吗啡耐受组）后,福尔马林诱发的c-Fos阳性神经元数量明显增加,与吗啡组相比,其脊髓Ⅰ-Ⅱ、Ⅲ-Ⅳ和Ⅴ-Ⅵ层c-Fos阳性神经元分别增加了164.9%、131.5%和125.3%（P〈0.05~0.01）;但隔天给予BAM8-22（吗啡＋BAM8-22组）则能明显增强慢性吗啡抑制c-Fos阳性神经元的表达,与吗啡耐受组相比,其脊髓Ⅰ-Ⅱ和Ⅴ-Ⅵ层c-Fos阳性神经元数量分别下降了66.6%和48.8%（P〈0.05~0.01）.在福尔马林引起的持续性痛中,BAM8-22延缓吗啡耐受是通过抑制脊髓背角伤害性神经元的活性来实现的。

The present study was designed to investigate the effects of intermittent co-administration of bovine adrenal medulla 8-22（ BAM8-22） on morphine tolerance through examining the expression of c-Fos in the lumbar spinal cord in formalin test. The results showed that formalin-evoked c-Fos positive neurons were remarkably increased in morphine tolerance when morphine was administrated daily for 6 days. The number of c-Fos positive neurons increased by 164. 9%,131. 5% and125. 3% in laminae Ⅰ- Ⅱ、Ⅲ- Ⅳ and Ⅴ- Ⅵ,respectively,compared with morphine group（ P 0. 05 ～ 0. 01）. Intermittent co-administration of BAM8-22（ morphine plus BAM8-22 group）remarkably enhanced the inhibition of chronic morphine on formalin-evoked c-Fos expression,the number of c-Fos positive neurons decreased by 66. 6% and 48. 8% in laminae Ⅰ- Ⅱ and Ⅴ- Ⅵ,respectively,compared with morphine in tolerant group（ P 0. 05 ～ 0. 01）. The present study provided evidence at a cellular level showing that BAM8-22 attenuate morphine tolerance by inhibiting the activation of nociceptive neurons in the spinal dorsal horn in formalin-induced persistent pain.