ArticleNeuron2019
Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System.
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Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117citing papers in PubMed
16.1field-weighted citation impact, top 1% of its field
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Who cites it
117 citing papers in PubMed, 202 citations in OpenAlex.
- Kappa Opioid Receptor Availability in Borderline Personality Disorder: An In Vivo Investigation With [Biological psychiatry · 2026Article
- Differences in ethanol drinking and nucleus accumbens opioid expression in male and female obesity-prone and obesity-resistant rats.Alcohol (Fayetteville, N.Y.) · 2026Article
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- Kappa opioid receptors in excitatory spinal neurons gate acute pain: evidence from mouse and human.bioRxiv : the preprint server for biology · 2026Article
- Kappa opioid receptor availability correlates with depressive symptom burden in chronic migraine: a preliminary investigation.The journal of headache and pain · 2026Article
- Effects of kappa-opioid receptor stimulation on addiction-related behavior in female rats: differences along the rostro-caudal axis of the nucleus accumbens shell.Psychopharmacology · 2026Article
- A corticothalamic circuit modulates pain sensitivity and mediates innate fear-induced analgesia in male mice.Nature communications · 2026Article
- Identifying affective state via clustering of temporal variability in limbic activity and mediating role of negative emotion.Molecular psychiatry · 2026Article
- CXCL7/CXCR2 in the paraventricular thalamus mediates obesity-related pain.Journal of neuroinflammation · 2026Article
- Psychological vulnerability and opioid medication use disorder risk in chronic pain: the mediating role of affective states and gender differences.Frontiers in public health · 2026Article
- Perspectives on Pain: A Narrative Review of Pain Beliefs, Coping, and Clinical Implications.Journal of pain research · 2026Review
- Down-regulation of gastrin-releasing peptide in medial orbitofrontal cortex to nucleus accumbens projections contributes to allodynia and negative affect.Science advances · 2025Article
- Dysregulation of Hedonic Processing in Chronic Pain: Insights from Preclinical Data.Brain sciences · 2025Review
- Kappa Opioid Receptors Control a Stress-Sensitive Brain Circuit and Drive Cocaine Seeking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- A switch in kappa opioid receptor signaling from inhibitory to excitatory induced by stress in a subset of cortically-projecting dopamine neurons.bioRxiv : the preprint server for biology · 2025Article
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- Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- A nociceptive amygdala-striatal pathway modulating affective-motivational pain.Science advances · 2025Article
- Shifted Balance Between Ventral Striatal Prodynorphin and Proenkephalin Biases Development of Cocaine Place Avoidance.Addiction biology · 2025Article
- A systematic review of the pain-related emotional and cognitive impairments in chronic inflammatory pain induced by CFA injection and its mechanism.IBRO neuroscience reports · 2025Review
57 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 2 countries.
Nicolas MassalyDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Bryan A CopitsDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Adrianne R Wilson-PoeDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Lucia HipólitoDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia 46100, Spain.
Tamara MarkovicDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Hye Jean YoonDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Shiwei LiuDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Marie C WalickiDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.
Dionnet L BhattiDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Sunil SirohiDepartment of Psychology, Washington State University, Pullman, WA 99164-4820, USA.
Amanda KlaasDepartment of Radiology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Brendan M WalkerDepartment of Psychology, Washington State University, Pullman, WA 99164-4820, USA.
Rachael NeveDepartment of Brain and Cognitive Science, Viral Gene Transfer Core, MIT, Cambridge, MA 02139-4307, USA.
Catherine M CahillDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kooresh I ShoghiDepartment of Radiology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA.
Robert W GereauDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA.
Jordan G McCallDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.
Ream Al-HasaniDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA. Electronic address: al-hasanir@wustl.edu.
Michael R BruchasDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: mbruchas@uw.edu.
Jose A MorónDepartment of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: jmoron-concepcion@wustl.edu.
Washington University in St. Louis · USUniversity of Health Sciences and Pharmacy · USWashington State University · USNeurobehavioral Systems · USUniversitat de València · ESUniversity of California, Los Angeles · US
Funding
The Role of Striosome Neurons in Mediating Opiod RewardP50DA005010 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WALWYN, WENDY M · 1987 to 2021
$30.7MWASHINGTON UNIVERSITY CO-CLINICAL IMAGING RESEARCH RESOURCEU24CA209837 · NCI · WASHINGTON UNIVERSITY · PI Li Ding, Shunqiang Li · 2017 to 2026
$6.3MMECHANISMS OF CENTRAL SENSITIZATIONR01NS048602 · NINDS · WASHINGTON UNIVERSITY · PI GEREAU, ROBERT W · 2004 to 2014
$4.2MThe Role of Kappa-Opioid Receptors in Alcohol Use DisordersR01AA020394 · NIAAA · WASHINGTON STATE UNIVERSITY · PI WALKER, BRENDAN M · 2011 to 2022
$3.8MDISSECTING DYNORPHIN-KAPPA OPIOID MEDIATED REINSTATEMENT OF NICOTINE PREFERENCER37DA033396 · NIDA · WASHINGTON UNIVERSITY · PI Michael R. Bruchas · 2018 to 2026
$3.8MMechanisms of Central SensitizationR01NS106953 · NINDS · WASHINGTON UNIVERSITY · PI GEREAU, ROBERT W · 2018 to 2022
$2.7MDissecting circuits mediating pain-induced alterations in motivated behaviorR01DA041781 · NIDA · WASHINGTON UNIVERSITY · PI MORON-CONCEPCION, JOSE A · 2017 to 2021
$2.3MRole of SK2 channels in morphine dependenceR01DA042499 · NIDA · WASHINGTON UNIVERSITY · PI MORON-CONCEPCION, JOSE A · 2017 to 2021
$1.9MDISSECTING DYNORPHIN-KAPPA OPIOID MEDIATED REINSTATEMENT OF NICOTINE PREFERENCER01DA033396 · NIDA · WASHINGTON UNIVERSITY · PI BRUCHAS, MICHAEL R. · 2013 to 2017
$1.9MDefining a role for kappa opioid system in affective behavior and drug escalation in painR01DA045463 · NIDA · WASHINGTON UNIVERSITY · PI MORON-CONCEPCION, JOSE A · 2018 to 2022
$1.8MWIRELESS IN VIVO OPTICAL CONTROL OF STRESS NEURAL CIRCUITS AND GPCR SIGNALINGR01DA037152 · NIDA · WASHINGTON UNIVERSITY · PI BRUCHAS, MICHAEL R. · 2013 to 2016
$1.2MUSING TRANSGENIC MICE TO EXAMINE THE ROLE OF CNIH3 VARIANTS IN OPIOID DEPENDENCER33DA041883 · NIDA · WASHINGTON UNIVERSITY · PI DOUGHERTY, JOSEPH D, MORON-CONCEPCION, JOSE A · 2018 to 2020
$1.1MNCI NIH HHS U24 CA209837NIAAA NIH HHS R01 AA020394NIDA NIH HHS K99 DA038725NIDA NIH HHS K99 DA041467NIDA NIH HHS P50 DA005010NIDA NIH HHS R00 DA038725NIDA NIH HHS R01 DA033396NIDA NIH HHS R01 DA037152NIDA NIH HHS R01 DA041781NIDA NIH HHS R01 DA042499NIDA NIH HHS R01 DA045463NIDA NIH HHS R21 DA041883NIDA NIH HHS R21 DA042581NIDA NIH HHS R33 DA041883NIDA NIH HHS R37 DA033396NINDS NIH HHS R01 NS048602NINDS NIH HHS R01 NS106953
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.
Indexed as
AffectAnimalsDynorphinsInflammationMiceMood DisordersNeural InhibitionNeuronal PlasticityNeuronsNucleus AccumbensPainRatsReceptors, Opioid, kappaDynorphinsReceptors, Opioid, kappa
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