Login

Journal Image
CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)
ISSN (Print): 1871-5273
ISSN (Online): 1996-3181
VOLUME: 11
ISSUE: 3
DOI: 10.2174/187152712800672490      Price:  $58









Janus Molecule I: Dichotomous Effects of COMT in Neuropathic vs Nociceptive Pain Modalities

img
Author(s): S. K. Segall, W. Maixner, I. Belfer, T. Wiltshire, Z. Seltzer and L. Diatchenko
Pages 222-235 (14)
Abstract:
The enzyme catechol-O-methyltransferase (COMT) has been shown to play a critical role in pain perception by regulating levels of epinephrine (Epi) and norepinephrine (NE). Although the key contribution of catecholamines to the perception of pain has been recognized for a long time, there is a clear dichotomy of observations. More than a century of research has demonstrated that increasing adrenergic transmission in the spinal cord decreases pain sensitivity in animals. Equally abundant evidence demonstrates the opposite effect of adrenergic signaling in the peripheral nervous system, where adrenergic signaling increases pain sensitivity. Viewing pain processing within spinal and peripheral compartments and determining the directionality of adrenergic signaling helps clarify the seemingly contradictory findings of the pain modulatory properties of adrenergic receptor agonists and antagonists presented in other reviews. Available evidence suggests that adrenergic signaling contributes to pain phenotypes through α1/2 and β2/3 receptors. While stimulation of α2 adrenergic receptors seems to uniformly produce analgesia, stimulation of α1 or β receptors produces either analgesic or hyperalgesic effects. Establishing the directionality of adrenergic receptor modulation of pain processing, and related COMT activity in different pain models are needed to bring meaning to recent human molecular genetic findings. This will enable the translation of current findings into meaningful clinical applications such as diagnostic markers and novel therapeutic targets for complex human pain conditions.
Keywords:
Adrenergic receptor signaling, COMT, intrathecal, nociception, neuropathic, pain, spinal cord, Catechol O Methyl Transferase, Haplotype, rs4680, Noxious stimuli, Epinephrin, Tempromandibular joint disorders
Affiliation:
Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USA.