Abstract
Pain is an integral part of the defense mechanisms required for survival. Several
hereditary syndromes of complete or almost complete insensitivity to pain have been
identified and include channelopathy-associated pain insensitivity, of which the most
likely candidate gene is the α-subunit of the voltage-gated sodium channel known as Na(v)1.7. Five hereditary sensory and autonomic neuropathy syndromes have been described.
Variable pain sensitivity in the general population has been linked to common variants
of the μ-opioid receptor and of the catecholamine-O-methyltransferase genes potentially leading to increased opioid tonus. Variants of
the guanosine triphosphate cyclohydrolase 1/dopa-responsive dystonia gene appear to
regulate nociception. Other candidate genes are the transient receptor potential cation
channel, subfamily 5 member 1, gene and the melanocortin-1 receptor gene. Candidate
genes for predicting opioid efficacy are drug-metabolizing enzymes and transporters—including
cytochrome P450, uridine 5′-diphosphate-glucuronosyltransferases, and adenosine triphosphate–binding
cassette transporters—that are involved in opioid metabolism. Most current knowledge
on the genetic regulation of pain has been derived from animal models developed mainly
in mice. Genomics has the potential to contribute to therapeutic advances with the
promising approach of using small interfering RNA in the control of neuropathic pain.
Knowledge of the genetic factors that affect opioid efficacy, metabolism, and adverse
effects has the potential for personalizing both acute and chronic pain management,
and for designing more useful opiate pain medications with lower adverse event profiles.
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Article info
Footnotes
Publication of this article was supported by the Collège International de Recherche Servier (CIRS).
STATEMENT OF CONFLICT OF INTEREST: The authors have nothing to disclose.
Identification
Copyright
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
