When it comes to pain, guys may be tougher than gals because they have more of a particular type of protein, new research suggests. Two studies published online this week by the Proceedings of the National Academy of Sciences implicate proteins known as GIRKs in sex-based differences in pain sensitivity in mice. The findings could help researchers develop new gender-specific treatments for discomfort.

Previous research had shown that males tend to have a higher threshold for pain than females do and that medications affect the sexes differently, although the precise mechanism remained unclear. In the new work, scientists tested analgesic drugs on mice unable to produce the GIRK2 protein. Allan I. Basbaum of Rockefeller University and his colleagues found that male mutants had lower pain thresholds than normal male mice. Female mutants exhibited a tolerance comparable to that of their normal counterparts, however, suggesting that GIRK2 is responsible for sex differences in pain sensitivity. Male mutants also did not respond as favorably to two pain medications, clonidine and morphine, as the normal animals did.

In the second study, R. Adron Harris of the University of Texas at Austin and his colleagues tested varying types of palliative drugs on the mutant mice and found that they all activate GIRK2. The drugs still had some effect on the mutant mice, however, so other pain-mediating mechanisms are most likely at work as well.