Understanding the ups and downs of pain modulation



Pain sensation can be dialed up or down depending on many factors such as expectations, experiences, and emotions. This capacity to enhance and suppress pain has been linked to changes in brain function. Consequently, abnormal changes in how the brain adjusts pain sensation may be the basis of abnormal, lasting pain, but little is known about the neuronal mechanisms that enable up and down pain regulation in the brain, and previous studies have shown conflicting results.


IRP researchers led by Yarimar Carrasquillo, Ph.D., combined state-of-the-art approaches and mouse behavioral studies to demonstrate that a brain region called the central amygdala (CeA) functions as a pain regulator, decreasing or intensifying pain-related behaviors in mice. The increase or decrease in pain was driven by opposite responses to painful stimuli in two types of neurons that are intermingled within the CeA. One CeA neuronal population showed pain-related increases in activity and promoted pain, whereas the second population showed pain-related decreases in activity and its activation decreased pain.


These findings resolve long-standing conflicting views of how the amygdala is involved in the modulation of pain. This study demonstrates that the CeA can both suppress and magnify pain and further identifies a cellular mechanism behind this process. Understanding the mechanisms underlying the brain’s ability to regulate pain is of vital importance for developing much-needed treatment options for chronic pain patients.


Wilson TD, Valdivia S, Khan A, Ahn HS, Adke AP, Martinez Gonzalez S, Sugimura YK, Carrasquillo Y. (2019). Dual and opposing functions of the central amygdala in the modulation of pain. Cell Rep. Oct 8;29(2):332-346.e5. doi: 10.1016/j.celrep.2019.09.011.

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This page was last updated on Friday, June 9, 2023