Cited by 313Neurotransmitter Receptor Influence on BehaviorPain Mechanisms and TreatmentsPain Management and Placebo Effect

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Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry

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Navratilova, Edita, Xie, Jennifer Y., Okun, Alec, Qu, Chaoling, Eyde, Nathan, Ci, Shuang, Ossipov, Michael H., King, Tamara, Fields, Howard L., Porreca, Frank·2012·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1214605109PMC PMC3528534

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Abstract

Relief of pain is rewarding. Using a model of experimental postsurgical pain we show that blockade of afferent input from the injury with local anesthetic elicits conditioned place preference, activates ventral tegmental dopaminergic cells, and increases dopamine release in the nucleus accumbens. Importantly, place preference is associated with increased activity in midbrain dopaminergic neurons and blocked by dopamine antagonists injected into the nucleus accumbens. The data directly support the hypothesis that relief of pain produces negative reinforcement through activation of the mesolimbic reward–valuation circuitry.

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Authors: Navratilova, E., Xie, J. Y., Okun, A., Qu, C., Eyde, N., Ci, S., Ossipov, M. H., King, T., Fields, H. L., & Porreca, F.
Affiliations: University of Arizona (US)
University of New England (US)
University of California, San Francisco (US)
ORCID: Navratilova, Edita
Xie, Jennifer Y.
Ossipov, Michael H.
King, Tamara
Fields, Howard L.
Porreca, Frank
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2012-11-26
Volume: 109
Issue: 50
Pages: 20709-20713
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1214605109
PMC: PMC3528534
OpenAlex: W2052380247
Cited by: 313
References: 48
Citations by year: 2026: 17 · 2025: 17 · 2024: 19 · 2023: 23 · 2022: 22 · 2021: 28 · 2020: 28 · 2019: 23 · 2018: 29 · 2017: 32 · 2016: 17 · 2015: 21 · 2014: 19 · 2013: 17
FWCI: 7.51
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute on Drug Abuse (R01DA034975)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Keywords: analgesia, negative reinforcement, mesolimbic reward circuitry, postoperative pain, conditioned place preference, ventral tegmental area, dopaminergic neurons, nucleus accumbens, dopamine release, local anesthetics, dopamine antagonists
MeSH terms: Afferent Pathways, Anesthetics, Local, Animals, Disease Models, Animal, Limbic System, Male, Models, Neurological, Nerve Block, Nucleus Accumbens, Pain, Pain, Postoperative, Postoperative Pain, Reinforcement, Psychology, Reward, Rats, Sprague-Dawley, Ventral Tegmental Area, Dopamine Antagonists, Rats

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Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry

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