The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry
Open accessAbstract
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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“mesolimbic dopamine projections from the ventral tegmental area (VTA) to the NAc are important in the analgesic effects induced by placebo and stress [55],[82], pain relief [58],[83], and the changes in motivated behavior caused by chronic pain [84].”
From Distinct Brain Systems Mediate the Effects of Nociceptive Input and Self-Regulation on Pain (2015) · cites this paper as [58]
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Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking
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Neurons for hunger and thirst transmit a negative-valence teaching signal
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Reward and motivation in pain and pain relief
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Metadata
- 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
- 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
- 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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