title: Placebo-induced analgesia in an operant pain model in rats.
abstract: Analgesia is particularly susceptible to placebo responses. Recent studies in humans have provided important insights into the neurobiology underlying placebo-induced analgesia. However, human studies provide incomplete mechanistic explanations of placebo analgesia because of limited capacity to use cellular, molecular, and genetic manipulations. To address this shortcoming, this article describes the development of a rat model of conditioned analgesia in an operant pain assay. Specifically, rats were conditioned to associate a placebo manipulation with the analgesic effect of 1mg/kg morphine (subcutaneously) on facial thermal pain. We found that conditioned (placebo) responding bore 3 of the hallmarks of placebo-induced analgesia: (1) strong interanimal variability in the response, (2) suppression by the opiate antagonist naloxone (5mg/kg subcutaneously), and (3) a positive predictive relationship between the unconditioned analgesic effect and the conditioned (placebo) effect. Because of the operant nature of the assay and the use of only a mild noxious thermal stimulus, we suggest that these results provide evidence of placebo-induced analgesia in a preclinical model that utilizes an affective behavioral end point. This finding may provide opportunities for invasive preclinical studies allowing greater understanding of placebo-induced analgesia, thus paving the way for avenues to harness its benefits.
authors.affiliation: College of Dentistry, Department of Orthodontics, University of Florida, Gainesville, FL, USA Department of Oral Surgery, University of Florida, Gainesville, FL, USA Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Nolan
authors.forename: Donald D
authors.initials: DD
authors.lastname: Price
authors.forename: Robert M
authors.initials: RM
authors.lastname: Caudle
authors.forename: Niall P
authors.initials: NP
authors.lastname: Murphy
authors.forename: John K
authors.initials: JK
authors.lastname: Neubert
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D010146:Pain / Q000175:diagnosis* / Q000188:drug therapy*; D015990:Placebo Effect; D051381:Rats; D054772:Rats, Hairless; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine