title: Expression and pharmacological modulation of visceral pain-induced conditioned place aversion in mice.
abstract: Pain encompasses both a sensory as well as an affective dimension and these are differentially processed in the brain and periphery. It is therefore important to develop animal models to reflect the non-reflexive assays in pain. In this study, we compared effects of the mu opioid receptor agonist morphine, the nonsteroidal anti-inflammatory drug ketoprofen and the kappa receptor opioid agonist U50,488H and antagonist JDTic on acetic acid-induced stretching and acetic acid-induced aversion in the condition place aversion (CPA) test in male ICR mice. Intraperitoneal administration of acetic acid (0.32-1%) was equipotent in stimulating stretching and CPA. Ketoprofen, morphine and U50,488H all inhibited the acid-induced stretching. Ketoprofen and morphine also blocked the acid-induced CPA but U50,488H failed to do so. The reversal ability of ketoprofen and morphine on acid-induced CPA is unique to pain-stimulated place aversion since these drugs failed to reduce non-noxious LiCl-induced CPA. Overall, this study characterized and validated a preclinical mouse model of pain-related aversive behavior that can be used to assess genetic and biological mechanisms of pain as well as improving the predictive validity of preclinical studies on candidate analgesics.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA; Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa 16059, Turkey. Electronic address: dbagdas@vcu.edu.
authors.forename: Deniz
authors.initials: D
authors.lastname: Bagdas
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
authors.forename: Pretal P
authors.initials: PP
authors.lastname: Muldoon
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Shakir
authors.initials: S
authors.lastname: AlSharari
authors.affiliation: Center for Drug Discovery, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, USA.
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
authors.forename: M Imad
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D007660:Ketoprofen / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D059265:Visceral Pain / Q000503:physiopathology*
chemical_list: C433814:7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010880:Piperidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D044005:Tetrahydroisoquinolines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D007660:Ketoprofen
keywords: Acetic acid; Analgesics; Conditioned place aversion; Mice; Pain