title: Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.
abstract: Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10-45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of βARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites.
authors: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors: R H
authors: RH
authors: Kline
authors: Orofacial Pain Center, College of Dentistry, University of Kentucky, Lexington, KY 40563, USA.
authors: F G
authors: FG
authors: Exposto
authors: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: S C
authors: SC
authors: O'Buckley
authors: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors: K N
authors: KN
authors: Westlund
authors: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: andrea_nackley@dentistry.unc.edu.
authors: A G
authors: AG
authors: Nackley
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000633:toxicity*; D002396:Catechols / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D006358:Hot Temperature; D008297:Male; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D010775:Photic Stimulation / Q000009:adverse effects; D011433:Propranolol / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors; D014110:Touch
chemical_list: D018663:Adrenergic Agents; D000700:Analgesics; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D002491:Central Nervous System Agents; D011619:Psychotropic Drugs; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D002394:Catechol O-Methyltransferase; C057726:OR486
keywords: allodynia; anxiety; catecholamines; hyperalgesia; operant; thermal place preference