Why a Man's Pain Is
Different Than a Woman's

NEW YORK (Reuters Health) - Men generally tolerate intense pain better than women, but painkillers tend to do a better job at masking pain in women than in men--and new research in mice offers an explanation why.

Two new studies demonstrate that a type of protein known as a GIRK may answer the question of why men have higher pain tolerances but lower sensitivity to painkillers than women. These results may one day help design painkillers that are tailored to the needs of each gender, according to the researchers.

In one report, the authors demonstrate that GIRK provides the only means by which male mice can wipe out pain via analgesics. While GIRK also appears to play an important role in how analgesics work in females, the research shows that females have additional means by which painkillers can mask their pain.

This finding may explain why analgesics, which can act on all of these painkilling pathways found only in women, can stomp out pain better in one sex than the other.

Another study demonstrates that GIRK2--a type of GIRK--may provide the means by which men increase their tolerance to pain relative to women.

Both of the reports appear in the online Early Edition of the Proceedings of the National Academy of Sciences.

In one of the studies, Dr. R. Adron Harris of the University of Texas at Austin and his colleagues performed experiments in mice that had been genetically modified so that they lacked GIRK2.

GIRK2 is a protein located on the surface of nerve cells. Pain results when potassium ions enter a cell via GIRK2; when a painkiller attaches to GIRK2, however, the entrance for potassium ions into the cell becomes closed off, thereby averting pain.

During the study, Harris and his team gave mice with or without GIRK2 a number of painkillers, such as alcohol and the active ingredient in marijuana. The mice were then placed on a hot plate that was warm, and the researchers measured whether the mice moved their paws because of the heat.

The investigators discovered that, in most cases, mice who received an analgesic but lacked GIRK2 appeared to feel pain more quickly than those with the protein, indicating that knocking out that protein blocked the effects of the painkillers.

However, female mice given a painkiller who lacked GIRK2 waited longer to react to the pain than male mice without GIRK2, suggesting that painkillers could quell some of the pain in females without GIRK2, perhaps by acting on other pain-quelling pathways besides those that use GIRK2.

"In males, (GIRK2) accounts for essentially all the pain relief," Harris told Reuters Health. "In females, it accounts for a fraction of the pain relief."

During the second study, Dr. Igor Mitrovic of the University of California at San Francisco and colleagues knocked out GIRK2 in male and female mice, and found that males had lower pain tolerances than males who carried GIRK2, while females with and without GIRK2 had similar responses to pain.

Deleting GIRK2 from the mice, consequently, deleted the differences in pain thresholds between males and females, suggesting that GIRK2 enables males to boost their thresholds for pain.

SOURCE: Proceedings of the National Academy of Sciences 2002;10.1073/pnas.0136823100, 0136822100.

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