title: Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry.
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.
authors.affiliation: Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Edita
authors.initials: E
authors.lastname: Navratilova
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Xie
authors.forename: Alec
authors.initials: A
authors.lastname: Okun
authors.forename: Chaoling
authors.initials: C
authors.lastname: Qu
authors.forename: Nathan
authors.initials: N
authors.lastname: Eyde
authors.forename: Shuang
authors.initials: S
authors.lastname: Ci
authors.forename: Michael H
authors.initials: MH
authors.lastname: Ossipov
authors.forename: Tamara
authors.initials: T
authors.lastname: King
authors.forename: Howard L
authors.initials: HL
authors.lastname: Fields
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008959:Models, Neurological; D009407:Nerve Block; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D010149:Postoperative Pain / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000779:Anesthetics, Local; D018492:Dopamine Antagonists