• Grace J Lee, Yea Jin Kim, Sang Wook Shim, Kihwan Lee, and Seog Bae Oh.
• Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
• Neuroscience. 2022 Jul 15; 495: 58-73.

AbstractFeeding 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 aICCaMKII-NAcSD2R projecting neurons in this CFA model. Besides, chemogenetic inhibition of aICCaMKII-NAcSD2R neural circuit suppressed chronic pain behavior while activation of this circuit reversed refeeding-induced analgesia. Thus, the present study suggests that aICCaMKII-NAcSD2R neural circuit mediates refeeding-induced analgesia, thereby serving as a potential therapeutic target to manage chronic pain.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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