While we believe pain is the same in all women of all hair colours, explained Mogil, our study shows women with red hair respond better to the pain-killing drug we tested than anyone else -- including men.
Previous research suggested the existence of a female-specific pain pathway in the brain. Analgesics that target receptors in this pathway, called kappa-opioid receptors, have been reported to work only in women. Using a technique called quantitative trait locus mapping, Mogil and his colleagues identified a candidate gene that may be responsible for this sex difference. Interestingly, the gene, called Mc1r, was first associated, not with neurological function, but with pigmentation. Variants of the gene cause red hair and fair skin in humans.
Redheads and painkillers
The scientists tested the effects of the kappa -specific analgesic on mutant mice with an inactive variation of Mc1r analogous to the "redhead" variation in humans. Although typical sex differences in analgesic effects were seen in normal mice, these differences disappeared in the mutants. The researchers then tested a clinically used kappa analgesic, pentazocine, on male and female humans with several Mc1r variations causing different hair colors and skin types. The Mc1r variations did not affect analgesic response to pentazocine in men, but caused a heightened response in redheaded, fair-skinned women. These results suggest that Mc1r modulates a kappa-specific pain pathway only in females.