Anterior Insular-nucleus Accumbens Pathway Controls Refeeding-induced Analgesia under Chronic Inflammatory Pain Condition. (15th July 2022)

• Record Type: Journal Article
• Authors: Lee, Grace J.; Kim, Yea Jin; Shim, Sang Wook; Lee, Kihwan; Oh, Seog Bae
• Is Part Of: Neuroscience. Volume 495(2022)
• Page Start: 58
• Page End: 73
• Publication Date: 2022-07-15
• Subjects: aIC anterior insular cortex -- CFA Complete Freund's adjuvant -- DREADD Designer receptors exclusively activated by designer drugs -- D2R dopamine type 2 receptor -- D1R dopamine type 1 receptor -- i.p. intraperitoneal -- NAc nucleus accumbens -- NAcC nucleus accumbens core -- NAcS nucleus accumbens shell; chronic inflammatory pain -- dopamine -- insular cortex -- nucleus accumbens -- refeeding; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2022.05.025
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: D2R antagonist reverses refeeding-induced analgesia under chronic pain conditions. aIC-NAcS circuit is activated in chronic inflammatory pain model. Refeeding suppresses aIC-NAcS circuit under chronic inflammatory pain condition. Chemogenetic activation of aIC-NAcS circuit reverses refeeding-induced analgesia. Abstract: 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 CaMKII –NAcS D2R projecting neurons in this CFA model. Besides, chemogenetic inhibition of aIC CaMKII –NAcS D2R neural circuit suppressed chronic pain behavior while activation of this circuit reversed refeeding-induced analgesia. Thus, the present study suggests that aIC CaMKII –NAcS D2R neural circuit mediates refeeding-induced analgesia, thereby serving as a potential therapeutic target to manage chronic pain.