Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
Tooth-Periodontium Complex Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Neuroscience. 2022 Jul 15;495:58-73. doi: 10.1016/j.neuroscience.2022.05.025. Epub 2022 May 25.
Feeding behaviors are closely associated with chronic pain in adult rodents. Our recent study revealed that 2 h refeeding after 24 h fasting (i.e., refeeding) attenuates pain behavior under chronic inflammatory pain conditions. However, while brain circuits mediating fasting-induced analgesia have been identified, the underlying mechanism of refeeding-induced analgesia is still elusive. Herein, we demonstrate that the neural activities in the nucleus accumbens shell (NAcS) and anterior insular cortex (aIC) were increased in a modified Complete Freund's Adjuvant (CFA)-induced chronic inflammatory pain condition, which was reversed by refeeding. We also found that refeeding reduced the enhanced excitability of aIC-NAcS projecting neurons in this CFA model. Besides, chemogenetic inhibition of aIC-NAcS neural circuit suppressed chronic pain behavior while activation of this circuit reversed refeeding-induced analgesia. Thus, the present study suggests that aIC-NAcS neural circuit mediates refeeding-induced analgesia, thereby serving as a potential therapeutic target to manage chronic pain.
摄食行为与成年啮齿动物的慢性疼痛密切相关。我们最近的研究表明，禁食 24 小时后再进食 2 小时（即再喂养）可减轻慢性炎症性疼痛条件下的疼痛行为。然而，虽然已经确定了介导禁食诱导镇痛的大脑回路，但再喂养诱导镇痛的潜在机制仍不清楚。本文中，我们证明了在改良的完全弗氏佐剂（CFA）诱导的慢性炎症性疼痛条件下，伏隔核壳（NAcS）和前岛叶皮层（aIC）的神经活动增加，再喂养则逆转了这一现象。我们还发现，再喂养降低了 CFA 模型中增强的 aIC-NAcS 投射神经元的兴奋性。此外，化学遗传抑制 aIC-NAcS 神经回路可抑制慢性疼痛行为，而激活该回路则逆转了再喂养诱导的镇痛作用。因此，本研究表明，aIC-NAcS 神经回路介导了再喂养诱导的镇痛作用，从而为管理慢性疼痛提供了一个潜在的治疗靶点。
