Location: Building 40, Rm. 1201/1203 or live on https://videocast.nih.gov/watch=52623
Title: Dialing pain up and down in the amygdala
Behavioral responses to painful stimuli can be amplified or suppressed by many factors, including expectations, experiences, and context. My lab is interested in identifying brain mechanisms underlying bidirectional modulation of pain and in determining whether these processes are sex dependent.
We use cellular physiology, molecular genetics, neuroanatomy, and behavioral rodent assays to tackle questions at molecular, cellular and circuit levels that we then causally link to pain-related behaviors. We have focused on the central amygdala (CeA), a forebrain limbic structure well positioned to link noxious stimuli to defense and affective responses. Our studies uncovered a dual function of the CeA in pain processing, showing that this brain region bidirectionally modulates pain and that the directionality of pain modulation is encoded by cell-type-specific changes in neuronal activity. At the cellular level, we have shown that genetically distinct CeA neurons are also morphologically and electrophysiologically distinct. At the circuit level, we identified and functionally characterized CeA efferent and afferent projections that modulate pain-related behaviors. Our studies have further shown important sex differences in brain mechanisms of pain modulation.
When studying pain, it is important to recognize that the experience of pain is complex and involves reciprocal interactions between physical pain and affective states. For example, painful stimuli are typically unpleasant and aversive while pain relief is typically rewarding and can induce positive affective states. In contrast, aversive stimuli like acute stress exposure or negative affective states like fear have been shown to result in robust analgesia. Our ongoing efforts are focused on studying brain mechanisms underlying the intersection of physical pain with affective states.
- Wilson TD, Valdivia S, Khan A, Ahn HS, Adke AP, Martinez Gonzalez S, Sugimura YK, Carrasquillo Y. Dual and Opposing Functions of the Central Amygdala in the Modulation of Pain.(external link) Cell Rep. 2019;29(2):332-346.e5.
- Adke AP, Khan A, Ahn HS, Becker JJ, Wilson TD, Valdivia S, Sugimura YK, Martinez Gonzalez S, Carrasquillo Y. Cell-Type Specificity of Neuronal Excitability and Morphology in the Central Amygdala.(external link) eNeuro. 2021;8(1).
- Francis-Malavé AM, Martínez González S, Pichardo C, Wilson TD, Rivera-García LG, Brinster LR, Carrasquillo Y. Sex differences in pain-related behaviors and clinical progression of disease in mouse models of colonic pain.(external link) Pain. 2023;164(1):197-215.
- Singh S, Wilson TD, Valdivia S, Benowitz B, Chaudhry S, Ma J, Adke AP, Soler-Cedeño O, Velasquez D, Penzo MA, Carrasquillo Y. An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice.(external link) Elife. 2022;11.
- Torres-Rodriguez JM, Wilson TD, Singh S, Torruella-Suárez ML, Chaudhry S, Adke AP, Becker JJ, Neugebauer B, Lin JL, Martinez Gonzalez S, Soler-Cedeño O, Carrasquillo Y. The parabrachial to central amygdala pathway is critical to injury-induced pain sensitization in mice. (external link) Neuropsychopharmacology. 2023.