A gene associated with red hair and fair skin may also be responsible for how females respond to painkillers, according to a study conducted by lead researcher Jeffrey Mogil, a McGill University psychology professor, and collaborators in the United States. Results of their study are to be released today in Proceedings of the National Academy of Sciences of the USA (article #03-0053).
"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.
"The Melanocortin-1 Receptor Gene Mediates Female-Specific Mechanisms of Analgesia in Mice and Humans," by Jeffrey S. Mogil, Sonya G. Wilson, Elissa J. Chesler, Andrew L. Rankin, Kumar V. S. Nemmani, William R. Lariviere, M. Kristina Groce, Margaret R. Wallace, Lee Kaplan, Roland Staud, Timothy J. Ness, Toni L. Glover, Magda Stankova, Alexander Mayorov, Victor J. Hruby, Judith E. Grisel and Roger B. Fillingim.
Jeffrey Mogil, the E.P. Taylor Professor of Pain Studies at McGill, is a repatriated Canadian who was recruited from the University of Illinois at Urbana-Champaign, where he first identified sex-specific genetic circuitry that governs the way males and females respond to pain. More generally, Mogil has been examining the genetic and environmental influences that combine to govern reactions to pain. At a minimum, pinpointing relevant genes can help doctors tailor dosages of drugs to each patient's needs. At best, Mogil's work may lead to new drugs providing life-saving pain relief.