Claustrum projections to the anterior cingulate modulate nociceptive and pain-associated behaviour

Abstract

The anterior cingulate cortex (ACC) processes nociceptive information and pain unpleasantness. The claustrum is a subcortical region that provides robust feed-forward inhibition onto the ACC, suggesting this circuit could play a role in modulating pathological states such as pain. However, the function of this circuit in the context of acute and chronic inflammatory pain is unclear. Here, we show that claustrocingulate neurons exhibit a bimodal pattern of activation following acute pain but are suppressed during states of chronic inflammatory pain. Molecular lesion and chemogenetic suppression of claustrocingulate neurons increased acute nociception but interfered with pain learning. Activation of this pathway rescued mechanical allodynia associated with chronic pain. Together, these results suggest claustrocingulate neurons are a critical component of the pain neuromatrix, and dysregulation of this connection may contribute to chronic pain.