School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.
Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States.
Pain. 2021 Mar 1;162(3):956-966. doi: 10.1097/j.pain.0000000000002177.
Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.
慢性疼痛与情感障碍高度共病,包括重性抑郁障碍。重性抑郁障碍的一个核心特征是对以前有奖励的活动失去兴趣。重性抑郁障碍还与消极情感偏见有关,其中认知过程受到情感状态的调节。我们实验室的先前工作表明,通过各种不同的操作产生的抑郁动物模型中,与奖励相关的学习和记忆受损。本研究在慢性疼痛的动物模型——部分隐神经损伤(PSNI)中,研究了与奖励相关的行为的不同方面。使用我们的奖励学习测定法,观察到在奖励学习方面存在障碍,但在蔗糖偏好方面没有差异,这与对奖励敏感性没有影响一致,与抑郁模型中的影响相似。在连续负对比任务中,在正常条件下或在奖励贬值时,慢性疼痛与奖励动机的变化无关,尽管假手术和 PSNI 组都表现出预期的负对比效应。在情感偏见测试中,PSNI 大鼠在用加巴喷丁治疗时表现出积极的情感偏见,而对照组则没有这种现象,这表明与药物的镇痛作用有关,这种药物诱导了相对更积极的情感状态。总之,这些数据表明,在这种慢性疼痛模型中,与奖励相关的认知存在变化,这与抑郁动物模型中的先前发现一致。加巴喷丁的作用表明,与疼痛相关的消极情感状态可能通过这种非典型的镇痛药物得到缓解。