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

Edita Navratilova, Jennifer Y. Xie, Alec Okun, Chaoling Qu, Nathan Eyde, Shuang Ci, Michael H. Ossipov, Tamara King, Howard L. Fields, Frank Porreca

Research output: Contribution to journalArticle

149 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)20709-20713
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 11 2012



  • Immunohistochemistry
  • In vivo microdialysis
  • Incision
  • Motivated behavior
  • Ventral tegmental area

ASJC Scopus subject areas

  • General

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