When a man is feeling no pain, blame GIRK2

[antiquity]

------------------------------------------------------------------------
POSTED AT 3:25 AMÂ*ESTÂ*Â*Â*Â*Tuesday, December 17


When a man is feeling no pain, blame GIRK2


Â*Â*
Â*Â*


By ANNE McILROY
From Tuesday's Globe and Mail

A Canadian researcher may have found a biological explanation 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 mutant male mice but still worked for the mutant 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 (correct spelling) 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.

The study also raises the possibility that males and females get a different kind of buzz from marijuana, alcohol and nicotine. Dr. Harris is planning a new set of experiments with mice to investigate.


http://www.globeandmail.com/servlet/ArticleNews/front/RTGAM/20021217/wxpain1217/Front/homeBN/breakingnews

[Max]

Why a Man's 'Ouch' Is Different Than a Woman's
Fri Dec 20, 1:47 PM ET Add Health - Reuters to My Yahoo!


By Alison McCook

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 (news - web sites).


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.