Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia 46100, Spain.
Neuron. 2019 May 8;102(3):564-573.e6. doi: 10.1016/j.neuron.2019.02.029. Epub 2019 Mar 13.
Negative affective states affect quality of life for patients suffering from pain. These maladaptive emotional states can lead to involuntary opioid overdose and many neuropsychiatric comorbidities. Uncovering the mechanisms responsible for pain-induced negative affect is critical in addressing these comorbid outcomes. The nucleus accumbens (NAc) shell, which integrates the aversive and rewarding valence of stimuli, exhibits plastic adaptations in the presence of pain. In discrete regions of the NAc, activation of the kappa opioid receptor (KOR) decreases the reinforcing properties of rewards and induces aversive behaviors. Using complementary techniques, we report that in vivo recruitment of NAc shell dynorphin neurons, acting through KOR, is necessary and sufficient to drive pain-induced negative affect. Taken together, our results provide evidence that pain-induced adaptations in the kappa opioid system within the NAc shell represent a functional target for therapeutic intervention that could circumvent pain-induced affective disorders. VIDEO ABSTRACT.
消极情绪状态会影响疼痛患者的生活质量。这些适应不良的情绪状态可导致非自愿性阿片类药物过量和许多神经精神共病。揭示导致疼痛引起的负面情绪的机制对于解决这些共病结果至关重要。伏隔核（NAc）壳，它整合了刺激的厌恶和奖励效价，在疼痛存在的情况下表现出可塑的适应性。在 NAc 的离散区域中，κ 阿片受体（KOR）的激活会降低奖励的强化特性并引起厌恶行为。使用互补技术，我们报告说，NAc 壳内 dynorphin 神经元的体内募集，通过 KOR 起作用，是驱动疼痛引起的负面情绪所必需且充分的。总之，我们的研究结果提供了证据，表明 NAc 壳内 κ 阿片系统的疼痛诱导适应是治疗干预的功能靶点，可避免疼痛引起的情感障碍。视频摘要。
