White Jason M
Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide, South Australia 5005, Australia.
Addict Behav. 2004 Sep;29(7):1311-24. doi: 10.1016/j.addbeh.2004.06.007.
One consequence of repeated drug administration is the development of adaptations in the nervous system, sometimes termed 'drug-opposite' responses. During administration, the effects of the drug are diminished by these adaptations (tolerance), while cessation of drug use results in the emergence of these drug-opposite responses as the withdrawal syndrome. Recent evidence on pain responses challenges this simple notion of withdrawal and suggests that aversive drug-opposite states may play a more important role in drug dependence than previously thought. While opioids such as heroin produce analgesia, people with a history of opioid self-administration are hypersensitive to certain kinds of pain during the time they are under the influence of the analgesic drug. This suggests that in pain systems, the drug-opposite response exceeds the pain inhibiting effect of the drug itself. This hyperalgesia is evident in people with a history of heroin use and is not modified by methadone or buprenorphine treatment but is reduced by long-term abstinence from opioids. This same pattern of the drug-opposite response exceeding the drug effect may also occur for mood. While opioids cause elevation of mood, commonly described as euphoria and reduction of emotional distress, methadone maintenance participants show significant negative mood disturbance relative to controls. Thus, for pain and mood, the chronic opioid user under the influence of the drug does not experience an opioid effect diminished by tolerance but a state opposite to the effect of the drug. Increases in drug concentration arising from administration serve only to reduce the degree of pain and mood disturbance. These aversive pain and mood states may contribute to the motivation for continued drug use and the dysfunction associated with drug dependence.
重复给药的一个后果是神经系统会产生适应性变化，有时被称为“药物相反”反应。在给药期间，这些适应性变化（耐受性）会减弱药物的效果，而停止使用药物则会导致这些药物相反反应以戒断综合征的形式出现。最近关于疼痛反应的证据对这种简单的戒断观念提出了挑战，并表明厌恶的药物相反状态在药物依赖中可能比以前认为的发挥更重要的作用。虽然海洛因等阿片类药物会产生镇痛作用，但有阿片类药物自我给药史的人在服用镇痛药物期间对某些类型的疼痛高度敏感。这表明在疼痛系统中，药物相反反应超过了药物本身的止痛效果。这种痛觉过敏在有海洛因使用史的人身上很明显，美沙酮或丁丙诺啡治疗无法改变这种情况，但长期停用阿片类药物可使其减轻。药物相反反应超过药物效果的这种相同模式也可能出现在情绪方面。虽然阿片类药物会导致情绪高涨，通常表现为欣快感和情绪困扰减轻，但与对照组相比，接受美沙酮维持治疗的参与者表现出明显的负面情绪困扰。因此，对于疼痛和情绪，受药物影响的慢性阿片类药物使用者并未经历因耐受性而减弱的阿片类药物效果，而是经历了与药物效果相反的状态。给药引起的药物浓度增加仅起到减轻疼痛和情绪困扰程度的作用。这些厌恶的疼痛和情绪状态可能会促使人们继续使用药物，并导致与药物依赖相关的功能障碍。
