Shirley and Stephan Hatos Center for Neuropharmacology, Semel Institute, Los Angeles, CA 90024-1759, USA.
Drug Alcohol Depend. 2010 May 1;108(3):156-65. doi: 10.1016/j.drugalcdep.2010.01.001. Epub 2010 Feb 25.
There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.
在治疗疼痛方面,很少有药物能优于阿片类药物。然而,由于人们对成瘾、戒断和对所有类型疼痛的疗效存在疑问,这些化合物远非缓解疼痛的神奇灵丹妙药。由于在不久的将来不太可能有其他类别的化合物取代阿片类药物,因此优化当前的阿片类药物治疗方法并遏制阿片类药物从预期的镇痛用途到非医疗滥用的惊人转移都非常重要。在优化阿片类药物治疗方法时,有必要提高对治疗疼痛的益处的临床认识,并将其与减少非医疗用途的转移的积极策略相结合。阿片类药物滥用问题的核心是阿片类药物系统在奖励回路中的作用,以及与重复使用阿片类药物相关的适应性过程,这些过程在戒断期间表现出来。将回顾阿片受体的新兴药理学见解,这些见解为开发具有降低成瘾性和减少对抗性过程的阿片类镇痛药提供了未来的希望。此外,随着对伤害感受回路和参与传递疼痛的分子的理解的增加,已经出现了新的治疗靶点,这些靶点可能单独或与当前的阿片类药物治疗联合使用,从而产生有效的镇痛效果。