A Neural Circuit for the Suppression of Peripheral Inflammation by Hunger

Abstract

Abstract Hunger is a primal biological drive that can initiate behavioral changes. Intuitively, hunger can inhibit behaviors such as sleep while simultaneously promoting foraging. Because pain can prevent an animal from seeking food we questioned if hunger could suppress pain. We found that food deprived mice reduce their response to inflammatory nociceptive stimuli. This reduction in nocifensive behavior during hunger is specific to inflammatory pain as the response to acute thermal and mechanical nociceptive stimuli remains intact. During hunger, agouti-related protein expressing (AgRP) neurons in the hypothalamus become active. AgRP neuron activation is both necessary and sufficient for feeding behavior and is thus a way to model hunger without the peripheral complications. Importantly, activating AgRP neurons recapitulates the analgesic effects of hunger. Because food deprivation reduces inflammatory pain responses, we next explored the influence of hunger and AgRP neuron activity on peripheral inflammation. To address this question, we measured paws after an injection of Complete Freund’s Adjuvant (CFA) in food deprived mice. We found that food deprivation was able to reduce CFA-induced paw inflammation compared to ad libitum fed controls. To assess the role of the AgRP circuit on inflammation, we measured CFA injected paws during optogenetic stimulation of AgRP neurons. Optogenetic activation of AgRP neurons rapidly reduces paw inflammation. This rapid and robust reduction in peripheral inflammation following activity in a CNS circuit suggests that AgRP neuron activity interacts with the immune system. Current experiments are aimed to determine the CNS à immune pathway that quickly reduces peripheral inflammation.