A Canadian researcher may have found a biological explanation for why females are more sensitive to pain than males, a discovery that could lead to painkillers tailored for each sex.

It is a common assumption that women can tolerate pain better than men because they cope with menstrual cramps and childbirth, but scientists established years ago that women are actually more sensitive to pain than men. They've also found that painkillers can affect men and women differently.

Now, two teams of researchers have made intriguing findings about why this may be. Working with mice, they found that males appear to have a natural pain-control system that females don't have. The key to that system is a protein called GIRK2, which plays a role in communication between brain cells.

Researchers at the University of California in San Francisco, led by Canadian neuroscientist Allan Basbaum, studied a mutant strain of mice that doesn't produce GIRK2. Without the protein, male mutants became much more sensitive to pain, as sensitive in fact as the females, whose pain threshold was unaffected by the mutation. Morphine no longer worked as a painkiller for the male mice but still worked for the females.

"The study suggests that males have a natural pain-control system that uses GIRK2 that isn't operating in females," Dr. Basbaum said in an interview.

A second team in Texas looked at the painkilling effects of alcohol, nicotine and marijuana in the mutant mice and documented the same effect. The males that didn't produce GIRK2 didn't get any pain relief from the drugs. The mutant females did.

Dr. Basbaum said that the pain pathways in mice and humans are similar, and that eventually the discovery could lead to different painkillers for men and women.

His next step is to figure out more about how GIRK2 works in mice. The researchers don't know whether males produce more GIRK2 than females or whether the protein is affected by female hormones.

His team and the one led by University of Texas neurobiologist Adrion Harris didn't set out to investigate differences in the way males and females feel pain. They made both discoveries inadvertently, trying to learn more about GIRK2 and the role it plays in the brain and spinal cord.

Jeffrey Mogil, a McGill University geneticist and pain researcher, says their work is exciting. Ten years ago, he found evidence that the system for modulating pain is different in male and female mice.

He recently made a discovery about the female pain pathway in mice, but can't discuss it until he publishes his findings in a scientific journal. Dr. Basbaum and Dr. Harris published their papers yesterday in the Proceedings of the National Academy of Sciences.

Dr. Mogil says he is convinced work on the sex differences underlying pain in males and females, including the developments made public yesterday, will lead to different painkillers for men and women.

"We are going to have blue pills and pink pills for pain," he said.

Dr. Mogil said that some studies in both animals and humans have shown a difference between males and females in sensitivity and tolerance to pain.

That is not always the case, he said, but when there is a difference it is the females who are more sensitive.