RT Journal Article
SR Electronic
T1 Melanocortin-1 receptor gene variants affect pain and μ-opioid analgesia in mice and humans
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 583
OP 587
DO 10.1136/jmg.2004.027698
VO 42
IS 7
A1 J S Mogil
A1 J Ritchie
A1 S B Smith
A1 K Strasburg
A1 L Kaplan
A1 M R Wallace
A1 R R Romberg
A1 H Bijl
A1 E Y Sarton
A1 R B Fillingim
A1 A Dahan
YR 2005
UL http://jmg.bmj.com/content/42/7/583.abstract
AB Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant μ-opioid receptor. Objective: To characterise sensitivity to pain and μ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/e mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. Results: C57BL/6-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the μ-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. Conclusions: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics.