1. Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System
- Author
-
Massaly, Nicolas, Copits, Bryan A, Wilson-Poe, Adrianne R, Hipólito, Lucia, Markovic, Tamara, Yoon, Hye Jean, Liu, Shiwei, Walicki, Marie C, Bhatti, Dionnet L, Sirohi, Sunil, Klaas, Amanda, Walker, Brendan M, Neve, Rachael, Cahill, Catherine M, Shoghi, Kooresh I, Gereau, Robert W, McCall, Jordan G, Al-Hasani, Ream, Bruchas, Michael R, and Morón, Jose A
- Subjects
Biomedical and Clinical Sciences ,Biological Psychology ,Neurosciences ,Psychology ,Pharmacology and Pharmaceutical Sciences ,Mental Health ,Drug Abuse (NIDA only) ,Chronic Pain ,Basic Behavioral and Social Science ,Substance Misuse ,Pain Research ,Behavioral and Social Science ,Good Health and Well Being ,Affect ,Animals ,Dynorphins ,Inflammation ,Mice ,Mood Disorders ,Neural Inhibition ,Neuronal Plasticity ,Neurons ,Nucleus Accumbens ,Pain ,Rats ,Receptors ,Opioid ,kappa ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - 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.
- Published
- 2019