Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.
BACKGROUND: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on kappa-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 mu-opioid receptor. OBJECTIVE: To characterise sensitivity to pain and mu-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. METHODS: Comparisons of spontaneous mutant C57BL/6-Mc1r(e/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-Mc1r(e/e) mutant mice and human redheads--both with non-functional MC1Rs--display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the mu-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.
Duke Scholars
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- Reference Values
- Receptors, Opioid, mu
- Receptor, Melanocortin, Type 1
- Pain Threshold
- Pain Measurement
- Pain
- Morphine Derivatives
- Morphine
- Mice, Mutant Strains
- Mice, Inbred C57BL
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Reference Values
- Receptors, Opioid, mu
- Receptor, Melanocortin, Type 1
- Pain Threshold
- Pain Measurement
- Pain
- Morphine Derivatives
- Morphine
- Mice, Mutant Strains
- Mice, Inbred C57BL