Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System

Nicolas Massaly, Bryan A. Copits, Adrianne R. Wilson-Poe, Lucia Hipólito, Tamara Markovic, Hye Jean Yoon, Shiwei Liu, Marie C. Walicki, Dionnet L. Bhatti, Sunil Sirohi, Amanda Klaas, Brendan M. Walker, Rachael Neve, Catherine M. Cahill, Kooresh I. Shoghi, Robert W. Gereau, Jordan G. McCall, Ream Al-Hasani, Michael R. Bruchas, Jose A. Morón

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Negative affective states affect quality of life for patients suffering from pain. These maladaptive emotional states can lead to involuntary opioid overdose and many neuropsychiatric comorbidities. Uncovering the mechanisms responsible for pain-induced negative affect is critical in addressing these comorbid outcomes. The nucleus accumbens (NAc) shell, which integrates the aversive and rewarding valence of stimuli, exhibits plastic adaptations in the presence of pain. In discrete regions of the NAc, activation of the kappa opioid receptor (KOR) decreases the reinforcing properties of rewards and induces aversive behaviors. Using complementary techniques, we report that in vivo recruitment of NAc shell dynorphin neurons, acting through KOR, is necessary and sufficient to drive pain-induced negative affect. Taken together, our results provide evidence that pain-induced adaptations in the kappa opioid system within the NAc shell represent a functional target for therapeutic intervention that could circumvent pain-induced affective disorders. Video Abstract: Massaly et al. identify a pain-induced enhancement in the kappa opioid system within nucleus accumbens, which drives pain-associated negative emotional states. These results provide a functional substrate for therapies that would circumvent pain-induced affective disorders.

Original languageEnglish
Pages (from-to)564-573.e6
JournalNeuron
Volume102
Issue number3
DOIs
StatePublished - May 8 2019

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    Massaly, N., Copits, B. A., Wilson-Poe, A. R., Hipólito, L., Markovic, T., Yoon, H. J., Liu, S., Walicki, M. C., Bhatti, D. L., Sirohi, S., Klaas, A., Walker, B. M., Neve, R., Cahill, C. M., Shoghi, K. I., Gereau, R. W., McCall, J. G., Al-Hasani, R., Bruchas, M. R., & Morón, J. A. (2019). Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System. Neuron, 102(3), 564-573.e6. https://doi.org/10.1016/j.neuron.2019.02.029