PT  - JOURNAL ARTICLE
AU  - Mogil, J S
AU  - Ritchie, J
AU  - Smith, S B
AU  - Strasburg, K
AU  - Kaplan, L
AU  - Wallace, M R
AU  - Romberg, R R
AU  - Bijl, H
AU  - Sarton, E Y
AU  - Fillingim, R B
AU  - Dahan, A
TI  - Melanocortin-1 receptor gene variants affect pain and μ-opioid analgesia in mice and humans
AID  - 10.1136/jmg.2004.027698
DP  - 2005 Jul 01
TA  - Journal of Medical Genetics
PG  - 583--587
VI  - 42
IP  - 7
4099  - http://jmg.bmj.com/content/42/7/583.short
4100  - http://jmg.bmj.com/content/42/7/583.full
SO  - J Med Genet2005 Jul 01; 42
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.