The persistence of negative affect in pain leads to co-morbid symptoms such as anhedonia and depression—major health issues in the United States. The neuronal circuitry and contribution of specific cellular populations underlying these behavioral adaptations remains unknown. A common characteristic of negative affect is a decrease in motivation to initiate and complete goal-directed behavior, known as anhedonia. We report that in rodents, inflammatory pain decreased the activity of ventral tegmental area (VTA) dopamine (DA) neurons, which are critical mediators of motivational states. Pain increased rostromedial tegmental nucleus inhibitory tone onto VTA DA neurons, making them less excitable. Furthermore, the decreased activity of DA neurons was associated with reduced motivation for natural rewards, consistent with anhedonia-like behavior. Selective activation of VTA DA neurons was sufficient to restore baseline motivation and hedonic responses to natural rewards. These findings reveal pain-induced adaptations within VTA DA neurons that underlie anhedonia-like behavior.

疼痛带来的负面影响持续存在，会导致快感缺乏和抑郁等共病症状——这是美国的主要健康问题。这些行为适应背后的神经元回路和特定细胞群的贡献仍然未知。负面情绪的一个共同特征是发起和完成目标导向行为的动机下降，称为快感缺失。我们报告说，在啮齿类动物中，炎症性疼痛会降低腹侧被盖区（VTA）多巴胺（DA）神经元的活性，而这些神经元是动机状态的关键介质。疼痛会增加 VTA DA 神经元上被盖核的抑制张力，使其兴奋性降低。此外，DA 神经元活性的降低与自然奖励动机的降低相关，这与快感缺失样行为一致。 VTA DA 神经元的选择性激活足以恢复基线动机和对自然奖励的享乐反应。这些发现揭示了 VTA DA 神经元内疼痛引起的适应，这是快感缺失样行为的基础。