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

• Published in: Cell reports (Cambridge) Vol. 29; no. 2; pp. 332 - 346.e5
• Main Authors: Wilson, Torri D., Valdivia, Spring, Khan, Aleisha, Ahn, Hye-Sook, Adke, Anisha P., Martinez Gonzalez, Santiago, Sugimura, Yae K., Carrasquillo, Yarimar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.10.2019; Elsevier
• Subjects: amygdala circuit; Animals; central amygdala; Central Amygdaloid Nucleus - physiopathology; chemogenetics; Enzyme Activation; Female; Hypersensitivity - complications; Hypersensitivity - physiopathology; intrinsic excitability; MAP Kinase Signaling System; Mice, Inbred C57BL; Models, Neurological; Nerve Tissue - injuries; Neuralgia - complications; Neuralgia - physiopathology; Neurons - metabolism; pain; pain pathways; parabrachial nucleus; protein kinase C delta; Protein Kinase C-delta - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Sciatic Nerve - injuries; Sciatic Nerve - pathology; somatostatin; Temperature; Touch; pain; amygdala circuit; central amygdala; somatostatin; chemogenetics; intrinsic excitability; protein kinase C delta; pain pathways; parabrachial nucleus
• DOI: 10.1016/j.celrep.2019.09.011
• ISSN: 2211-1247

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. [Display omitted] •The CeA can both attenuate and exacerbate pain-related behaviors in mice•Injury induces cell-type-specific bidirectional changes in excitability in the CeA•Increased firing in CeA-PKCδ neurons drives amplification of pain-related responses•Activation of CeA-Som neurons attenuates injury-induced pain-related behaviors 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.