Neuroscience 2005 Abstract
| Presentation Number: | 393.14 |
|---|---|
| Abstract Title: | Catechol-<i>O</i>-methyltransferase modulates pain behavior and cytokine production via β2/3-adrenergic receptor mechanisms. |
| Authors: |
Nackley, A. G.*1
; Faison, J. F.1
; Lambeth, B. L.1
; Fecho, K.1
; Diatchenko, L. B.1
; Maixner, W.1
1Center for Neurosensory Disorders, Univ. of North Carolina, Chapel Hill, NC |
| Primary Theme and Topics |
Sensory and Motor Systems - Pain -- Pain transduction molecules and channels |
| Session: |
393. Pain Transduction Molecules and Channels I Poster |
| Presentation Time: | Monday, November 14, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # U10 |
| Keywords: | norepinephrine, epinephrine, hyperalgesia, allodynia |
Catechol-O-methyltransferase (COMT) has recently been implicated in the modulation of persistent pain. We demonstrated that common human haplotypes of the COMT gene are associated with pain sensitivity and the risk for temporomandibular disorder (TMD), a chronic musculoskeletal pain condition (Diatchenko et al, Hum Mol Gen 2005). Haplotypes coding for low COMT activity are associated with high pain sensitivity and increased TMD incidence. Furthermore, reductions in COMT activity result in heightened pain sensitivity in animal models via actions at β-adrenergic receptors (Nackley et al, SfN 2004). The present study was conducted to elucidate the specific receptor mechanism/s whereby COMT modulates pain sensitivity. Separate groups of rats received intraperitoneal (i.p.) injections of the β1 antagonist betaxolol, the β2 antagonist ICI118,551, the β3 antagonist SR59230A, or vehicle 10 min prior to i.p. administration of the COMT inhibitor OR486 or vehicle. Administration of OR486 significantly increased the production of proinflammatory cytokines (TNFα, IL-1β, and IL-6) as well as pain behavior evoked by mechanical and thermal stimuli. Administration of β2 or β3 antagonists reduced the development of COMT-dependent pain sensitivity and cytokine synthesis; however, only a partial blockade was achieved. In a subsequent study, ICI118,551 and SR59230A were coadministered prior to the administration of OR486. Coadministration of β2 and β3 antagonists completely normalized behavioral responses to mechanical and thermal stimuli. Administration of the β1 antagonist failed to alter OR486-induced pain sensitivity. These data provide the first direct evidence that reduced levels of COMT lead to increased pain sensitivity and proinflammatory cytokine production via β2/3-adrenergic mechanisms. Furthermore, the combined activation of both β2 and β3 may be necessary to produce the maximum degree of COMT-dependent pain sensitivity.
Supported by DE007333 to AN, DE016558 to LD, and NS045685 to WM
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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