Barattini Angela E, Pahng Amanda R
Department of Physiology, LSU Health Sciences Center, New Orleans, LA, USA.
Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA.
Psychopharmacology (Berl). 2025 Jan;242(1):1-26. doi: 10.1007/s00213-024-06719-1. Epub 2024 Nov 20.
Opioid analgesics are the most effective medications used for the treatment of pain, however there are significant risks associated with repeated opioid use including opioid misuse and opioid use disorder development. Chronic pain affects millions of adults in the United States, and opioid misuse is often comorbid with pain conditions in individuals who are repeatedly treated with opioids. In addition to providing pain relief, opioids produce rewarding effects, but in chronic pain states, reward processing can become dysregulated. The conditioned place preference task is commonly used to measure the rewarding properties of opioids in rodents. During this task, opioid administration is paired with a distinct environment through repeated conditioning and the change in an animal's preference for the paired environment indicates whether the opioid is rewarding or not.
Rodent pain models can be combined with conditioned place preference to examine the effects of pain on opioid reward. The existing preclinical literature on pain effects on conditioned place preference is conflicting, where pain conditions have been reported to enhance, suppress, or have no effect on opioid reward. This review will discuss several factors that may contribute to these discordant findings including conditioning session duration and number, rodent strain differences in opioid sensitivity, analgesic properties of opioids at tested doses, locomotor effects at tested doses, and diurnal variation in pain sensitivity. Future studies should consider how these factors contribute to opioid conditioned place preference in both pain and pain-free animals to have a better understanding of the interactions between pain and opioid reward.
阿片类镇痛药是治疗疼痛最有效的药物,然而,反复使用阿片类药物存在重大风险,包括阿片类药物滥用和阿片类药物使用障碍的发展。慢性疼痛影响着美国数百万成年人,在反复接受阿片类药物治疗的个体中,阿片类药物滥用往往与疼痛状况并存。除了缓解疼痛外,阿片类药物还会产生奖赏效应,但在慢性疼痛状态下,奖赏处理可能会失调。条件性位置偏爱任务通常用于测量啮齿动物中阿片类药物的奖赏特性。在这个任务中,通过反复条件化,将阿片类药物给药与一个独特的环境配对,动物对配对环境偏好的变化表明阿片类药物是否具有奖赏性。
啮齿动物疼痛模型可与条件性位置偏爱相结合,以研究疼痛对阿片类药物奖赏的影响。现有的关于疼痛对条件性位置偏爱影响的临床前文献存在矛盾,有报道称疼痛状况可增强、抑制或对阿片类药物奖赏无影响。本综述将讨论可能导致这些不一致结果的几个因素,包括条件化训练的持续时间和次数、啮齿动物品系在阿片类药物敏感性上的差异、测试剂量下阿片类药物的镇痛特性、测试剂量下的运动效应以及疼痛敏感性的昼夜变化。未来的研究应考虑这些因素如何影响疼痛和无疼痛动物的阿片类条件性位置偏爱,以便更好地理解疼痛与阿片类药物奖赏之间的相互作用。