Paraventricular hypothalamic input to anterior cingulate cortex controls food preferences in chronic visceral pain

Abstract Chronic visceral pain is commonly accompanied by changes in food preference; however, the underlying neural circuitry mechanisms remain unclear. This study aimed to investigate the effects of chronic visceral pain on food preference and neural circuitry. Chronic visceral hyperalgesia in mice was induced by neonatal colonic inflammation (NCI). We identified a neural circuit involving cholecystokinin neurons in the paraventricular hypothalamus (PVHCCK) projecting to glutamatergic neurons in the anterior cingulate cortex (ACCGlu). Chemogenetic inhibition of the PVHCCK to ACCGlu circuit reduced visceral pain and food preference switched from sugar to fat, which reversed by agonist of cholecystokinin receptors (CCKBRs) in the ACC. Chemogenetic activation of PVHCCK to ACCGlu circuit increased visceral pain and food preference switched from fat to sugar, which reversed by antagonist of CCKBRs in the ACC. Therefore, the PVHCCK to ACCGlu circuit encodes changes in food preference of mice during chronic visceral pain. Interventions targeting this neural circuitry maybe a potential therapeutic strategy for patients with chronic visceral pain.