Dual and Opposing Functions of the Central Amygdala in the Modulation of Pain

Abstract

Summary: Pain perception is essential for survival and can be amplified or suppressed by expectations, experiences, and context. The neural mechanisms underlying bidirectional modulation of pain remain largely unknown. Here, we demonstrate that the central nucleus of the amygdala (CeA) functions as a pain rheostat, decreasing or increasing pain-related behaviors in mice. This dual and opposing function of the CeA is encoded by opposing changes in the excitability of two distinct subpopulations of GABAergic neurons that receive excitatory inputs from the parabrachial nucleus (PB). Thus, cells expressing protein kinase C-delta (CeA-PKCδ) are sensitized by nerve injury and increase pain-related responses. In contrast, cells expressing somatostatin (CeA-Som) are inhibited by nerve injury and their activity drives antinociception. Together, these results demonstrate that the CeA can amplify or suppress pain in a cell-type-specific manner, uncovering a previously unknown mechanism underlying bidirectional control of pain in the brain. : The brain can bidirectionally influence behavioral responses to painful stimuli. Wilson et al identify a cellular mechanism underlying a pain rheostat system within the forebrain, with activation of CeA-Som neurons attenuating pain-related responses and increases in the activity of CeA-PKCδ neurons promoting amplification of pain-related behaviors following injury. Keywords: pain, central amygdala, intrinsic excitability, somatostatin, protein kinase C delta, parabrachial nucleus, amygdala circuit, pain pathways, chemogenetics