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

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.

• Authors: 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 4th, Jordan G McCall, Ream Al-Hasani, Michael R Bruchas, Jose A Morón
• Journal: Neuron (Neuron) Vol. 102 Issue 3 Pg. 564-573.e6 (05 08 2019) ISSN: 1097-4199 [Electronic] United States
• PMID: 30878290 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Video-Audio Media)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Opioid, kappa
• Dynorphins

Topics

• Affect (physiology)
• Animals
• Dynorphins (metabolism)
• Inflammation (complications, metabolism, psychology)
• Mice
• Mood Disorders (etiology, metabolism, psychology)
• Neural Inhibition
• Neuronal Plasticity
• Neurons (metabolism)
• Nucleus Accumbens (cytology, metabolism)
• Pain (complications, metabolism, psychology)
• Rats
• Receptors, Opioid, kappa (metabolism)