Chemogenetic inhibition of pain-related neurons in the posterior insula cortex reduces mechanical hyperalgesia and anxiety-like behavior during acute pain.

Pain is a complex phenomenon that involves sensory, emotional, and cognitive components. The posterior insula cortex (pIC) has been shown to integrate multisensory experience with emotional and cognitive states. However, the involvement of the pIC in the regulation of affective behavior in pain remains unclear. Here, we investigate the role of pain-related pIC neurons in the regulation of anxiety-like behavior during acute pain. We combined a chemogenetic approach with targeted recombination in active populations (TRAP) in mice. Global chemogenetic inhibition of pIC neurons attenuates chemically-induced mechanical hypersensitivity without affecting pain-related anxiety-like behavior. In contrast, inhibition of pain-related pIC neurons reduces both mechanical hypersensitivity and pain-related anxiety-like behavior. The present study provides important insights into the role of pIC neurons in the regulation of sensory and affective pain-related behavior.