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Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.

Publication ,  Journal Article
Kline, RH; Exposto, FG; O'Buckley, SC; Westlund, KN; Nackley, AG
Published in: Neuroscience
April 2, 2015

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.

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Published In

Neuroscience

DOI

EISSN

1873-7544

Publication Date

April 2, 2015

Volume

290

Start / End Page

561 / 569

Location

United States

Related Subject Headings

  • Touch
  • Time Factors
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Psychotropic Drugs
  • Propranolol
  • Photic Stimulation
  • Pain
  • Neurology & Neurosurgery
  • Male
 

Citation

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Kline, R. H., Exposto, F. G., O’Buckley, S. C., Westlund, K. N., & Nackley, A. G. (2015). Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat. Neuroscience, 290, 561–569. https://doi.org/10.1016/j.neuroscience.2015.01.064
Kline, R. H., F. G. Exposto, S. C. O’Buckley, K. N. Westlund, and A. G. Nackley. “Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.Neuroscience 290 (April 2, 2015): 561–69. https://doi.org/10.1016/j.neuroscience.2015.01.064.
Kline RH, Exposto FG, O’Buckley SC, Westlund KN, Nackley AG. Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat. Neuroscience. 2015 Apr 2;290:561–9.
Kline, R. H., et al. “Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.Neuroscience, vol. 290, Apr. 2015, pp. 561–69. Pubmed, doi:10.1016/j.neuroscience.2015.01.064.
Kline RH, Exposto FG, O’Buckley SC, Westlund KN, Nackley AG. Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat. Neuroscience. 2015 Apr 2;290:561–569.
Journal cover image

Published In

Neuroscience

DOI

EISSN

1873-7544

Publication Date

April 2, 2015

Volume

290

Start / End Page

561 / 569

Location

United States

Related Subject Headings

  • Touch
  • Time Factors
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Psychotropic Drugs
  • Propranolol
  • Photic Stimulation
  • Pain
  • Neurology & Neurosurgery
  • Male