Crain S M, Shen K F
Dept. of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Neurochem Res. 1996 Nov;21(11):1347-51. doi: 10.1007/BF02532375.
Electrophysiologic studies of opioid effects on nociceptive types of dorsal root ganglion (DRG) neurons in organotypic cultures have shown that morphine and most mu, delta, and kappa opioid agonists can elicit bimodal excitatory as well as inhibitory modulation of the action potential duration (APD) of these cells. Excitatory opioid effects have been shown to be mediated by opioid receptors that are coupled via Gs to cyclic AMP-dependent ionic conductances that prolong the APD, whereas inhibitory opioid effects are mediated by opioid receptors coupled via Gi/Go to ionic conductances that shorten the APD. Selective blockade of excitatory opioid receptor functions by low (ca. pM) concentrations of naloxone, naltrexone, etorphine and other specific agents markedly increases the inhibitory potency of morphine or other bimodally acting agonists and attenuates development of tolerance/dependence. These in vitro studies have been confirmed by tail-flick assays showing that acute co-treatment of mice with morphine plus ultra-low-dose naltrexone or etorphine remarkably enhances the antinociceptive potency of morphine whereas chronic co-treatment attenuates development of tolerance and naloxone-precipitated withdrawal-jumping symptoms.
对器官型培养物中背根神经节（DRG）神经元伤害感受类型的阿片类药物作用进行的电生理研究表明，吗啡以及大多数μ、δ和κ阿片类激动剂可对这些细胞的动作电位持续时间（APD）引发双相兴奋性以及抑制性调节。兴奋性阿片类药物作用已被证明是由通过Gs与环磷酸腺苷依赖性离子电导偶联的阿片类受体介导的，这些离子电导会延长APD，而抑制性阿片类药物作用则由通过Gi/Go与缩短APD的离子电导偶联的阿片类受体介导。低（约pM）浓度的纳洛酮、纳曲酮、埃托啡和其他特定药物对兴奋性阿片类受体功能的选择性阻断，可显著提高吗啡或其他双相作用激动剂的抑制效力，并减弱耐受性/依赖性的发展。这些体外研究已通过甩尾试验得到证实，该试验表明，吗啡与超低剂量纳曲酮或埃托啡对小鼠进行急性联合治疗，可显著增强吗啡的镇痛效力，而慢性联合治疗则可减弱耐受性的发展以及纳洛酮诱发的戒断跳跃症状。
