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Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors.

Publication ,  Journal Article
Ciszek, BP; O'Buckley, SC; Nackley, AG
Published in: Anesthesiology
May 2016

BACKGROUND: Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via β-adrenergic receptor (βAR) activation. The contribution of distinct βAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation. METHODS: Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal βARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained βAR antagonists peripherally, spinally, or supraspinally alongside OR486. RESULTS: The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective βAR antagonist propranolol, the β2AR antagonist ICI-118,511, or the β3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity. CONCLUSIONS: Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting βAR antagonists may benefit chronic pain patients.

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Published In

Anesthesiology

DOI

EISSN

1528-1175

Publication Date

May 2016

Volume

124

Issue

5

Start / End Page

1122 / 1135

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Propanolamines
  • Physical Stimulation
  • Peripheral Nervous System
  • Pain Measurement
  • Pain
  • Male
  • Injections, Spinal
 

Citation

APA
Chicago
ICMJE
MLA
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Ciszek, B. P., O’Buckley, S. C., & Nackley, A. G. (2016). Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors. Anesthesiology, 124(5), 1122–1135. https://doi.org/10.1097/ALN.0000000000001070
Ciszek, Brittney P., Sandra C. O’Buckley, and Andrea G. Nackley. “Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors.Anesthesiology 124, no. 5 (May 2016): 1122–35. https://doi.org/10.1097/ALN.0000000000001070.
Ciszek BP, O’Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122–35.
Ciszek, Brittney P., et al. “Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors.Anesthesiology, vol. 124, no. 5, May 2016, pp. 1122–35. Pubmed, doi:10.1097/ALN.0000000000001070.
Ciszek BP, O’Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122–1135.

Published In

Anesthesiology

DOI

EISSN

1528-1175

Publication Date

May 2016

Volume

124

Issue

5

Start / End Page

1122 / 1135

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Propanolamines
  • Physical Stimulation
  • Peripheral Nervous System
  • Pain Measurement
  • Pain
  • Male
  • Injections, Spinal