@article{a73286467c294d9b9340efe966fd4a7e,
title = "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: 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.",
author = "Nicolas Massaly and Copits, {Bryan A.} and Wilson-Poe, {Adrianne R.} and Lucia Hip{\'o}lito and Tamara Markovic and Yoon, {Hye Jean} and Shiwei Liu and Walicki, {Marie C.} and Bhatti, {Dionnet L.} and Sunil Sirohi and Amanda Klaas and Walker, {Brendan M.} and Rachael Neve and Cahill, {Catherine M.} and Shoghi, {Kooresh I.} and Gereau, {Robert W.} and McCall, {Jordan G.} and Ream Al-Hasani and Bruchas, {Michael R.} and Mor{\'o}n, {Jose A.}",
note = "Funding Information: We would like to thank all members from the Moron-Concepcion, Bruchas and Al-Hasani laboratories for their help throughout the completion of the current study and Lindsay Lueptow for the complementary analysis of GTPgammaS slices. This work was supported by US National Institutes of Health (NIH) grant DA041781 (J.A.M.), DA042581 (J.A.M.), DA042499 (J.A.M.), DA041883 (J.A.M.), DA045463 (J.A.M.), NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation (J.A.M.), DA033396 (M.R.B.), DA037152 (M.R.B.), R01-NS106953 (R.W.G.), AA020394 (B.M.W.), K99/R00-DA038725 (R.A.), K99-DA041467 (A.R.W.-P.), Philippe Foundation (N.M.), the “Spanish Ministerio de Economia y Competitividad” MINECO PSI2016-77895-R (L.H.), the Mallinckrodt Institute of Radiology at Washington University from pilot grant 16-014 to support the positron emission tomography studies, the Hope Center Viral Vectors Core at Washington University School of Medicine. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = may,
day = "8",
doi = "10.1016/j.neuron.2019.02.029",
language = "English",
volume = "102",
pages = "564--573.e6",
journal = "Neuron",
issn = "0896-6273",
number = "3",
}