Male and female mice process pain differently, study finds
June 30, 2015 12:10 PM Subscribe
New research into the pain processing of mice has found male and female mice process pain differently, and the discovery may also apply to other species, including humans. Scientists are now questioning what this means for the future of medical research, which until now, has had a strong bias towards experimenting on male mice.
Sex bias in the subject of medical research has been an issue for a long time. This disparity has had a variety of negative effects on women's outcomes in health care. Last year, the NIH rolled out a policy of requiring medical researchers to use both male and female subjects in animal studies.
Previously.
Sex bias in the subject of medical research has been an issue for a long time. This disparity has had a variety of negative effects on women's outcomes in health care. Last year, the NIH rolled out a policy of requiring medical researchers to use both male and female subjects in animal studies.
Previously.
The pain gap between genders has also been documented in humans -- A recent editorial on the issue in humans.
It's a complicated problem. Women are more likely to get many diseases that cause pain, are less likely to have their pain treated seriously when they seek medical attention, are less likely to be given pain medications, and don't respond as well to some pain medications.
posted by pie ninja at 12:38 PM on June 30, 2015 [5 favorites]
It's a complicated problem. Women are more likely to get many diseases that cause pain, are less likely to have their pain treated seriously when they seek medical attention, are less likely to be given pain medications, and don't respond as well to some pain medications.
posted by pie ninja at 12:38 PM on June 30, 2015 [5 favorites]
I am going to print up everyone of these in huge stacks and bring them and bring them to every doctor I see. Maybe leave them around waiting rooms.
posted by [insert clever name here] at 1:03 PM on June 30, 2015
posted by [insert clever name here] at 1:03 PM on June 30, 2015
Being a red-headed man means getting a tiny window into how much this shit sucks every time I step into the dentist's office.
There are five or six different - and potentially cumulative - mutations responsible for red-headedness. I have whichever one means needing twice as much novocaine not to shriek through a routine filling (despite an otherwise exceptionally high pain tolerance), plus a virtual guarantee that even a double dose will wear off in ~45 minutes.
Explaining this to every dentist, every goddamn visit, gets really fucking old really fucking fast. The general lack of empathy and recurring "oh that's right I forgot you have that weird genetic ...thing" are similarly grating.
I have an inkling how fucking pissed I'd be if that shit carried over outside the dentist's office, and my deepest sympathies go out to anybody living that, for whatever reason.
posted by Ryvar at 1:46 PM on June 30, 2015 [4 favorites]
There are five or six different - and potentially cumulative - mutations responsible for red-headedness. I have whichever one means needing twice as much novocaine not to shriek through a routine filling (despite an otherwise exceptionally high pain tolerance), plus a virtual guarantee that even a double dose will wear off in ~45 minutes.
Explaining this to every dentist, every goddamn visit, gets really fucking old really fucking fast. The general lack of empathy and recurring "oh that's right I forgot you have that weird genetic ...thing" are similarly grating.
I have an inkling how fucking pissed I'd be if that shit carried over outside the dentist's office, and my deepest sympathies go out to anybody living that, for whatever reason.
posted by Ryvar at 1:46 PM on June 30, 2015 [4 favorites]
I suppose this makes sense, biologically, since there is no way I, as a man, would be able to tolerate the pain of childbirth. On the other hand, I broke my hip in a mountain bike crash and only took NSAIDs for the bruise. That pain was tolerable, and I didn't know I'd broken the hip. People say you will know when you've broken something, but in multiple injuries, I've managed just fine.
I had a bit of skin cancer removed from my forehead years ago, and I told the doctor that I could feel what he was doing. He injected me with more pain killer, and told me that when I go to the dentist, I need to explain that the Novocaine wears off faster than normal. I am terrified of the dentist because, when I was younger, my dentist filled a tooth without any anesthetic because "It was not deep enough to justify Novocaine and I was too young." That was pain I never want to experience again, and even routine cleanings are hard for me.
I know several women who are in chronic pain, and they suffer...truly suffer. Nothing traditional works for them, so I'm hoping that this research yields a solution to their mostly ineffective pain management.
posted by Chuffy at 2:00 PM on June 30, 2015
I had a bit of skin cancer removed from my forehead years ago, and I told the doctor that I could feel what he was doing. He injected me with more pain killer, and told me that when I go to the dentist, I need to explain that the Novocaine wears off faster than normal. I am terrified of the dentist because, when I was younger, my dentist filled a tooth without any anesthetic because "It was not deep enough to justify Novocaine and I was too young." That was pain I never want to experience again, and even routine cleanings are hard for me.
I know several women who are in chronic pain, and they suffer...truly suffer. Nothing traditional works for them, so I'm hoping that this research yields a solution to their mostly ineffective pain management.
posted by Chuffy at 2:00 PM on June 30, 2015
Bizarre. So female but not male SCID sufferers should be more resistant mechanical pain hypersensitivity. And female patients, but not male patients, would likely experience less pain after organ transplant, since the immunosuppressive agents work particularly well on T cells. I cannot fathom why such a pathway would evolve with such sexual dimorphism.
Jonathan Fisher reports for Business Insider that in 2009, male bias in neuroscience "saw single-sex studies of male animals outnumbering those of females 5.5 to 1".
This is strange. We work predominantly with female mice (not in neuroscience) because they are much less likely to fight. Nothing screws up an experiment faster than a massive skin wound that arises because the mouse vendor has not included the dominant male in your cage and the mice have fought to re-establish dominance. The female mice are also less aggressive, so I would have thought pain researchers who are actively distressing their animals would want to minimise their risk of being bitten!
posted by kisch mokusch at 3:01 PM on June 30, 2015 [4 favorites]
Jonathan Fisher reports for Business Insider that in 2009, male bias in neuroscience "saw single-sex studies of male animals outnumbering those of females 5.5 to 1".
This is strange. We work predominantly with female mice (not in neuroscience) because they are much less likely to fight. Nothing screws up an experiment faster than a massive skin wound that arises because the mouse vendor has not included the dominant male in your cage and the mice have fought to re-establish dominance. The female mice are also less aggressive, so I would have thought pain researchers who are actively distressing their animals would want to minimise their risk of being bitten!
posted by kisch mokusch at 3:01 PM on June 30, 2015 [4 favorites]
Women get so much shit about their bodies - how we present ourselves, how we use our bodies, how our bodies "are distracting," what we do with our bodies, and the whole pantheon of how we're different biologically as a reason why we shouldn't do things. There's just so much interest in our bodies, all the time, including laws defining how we get to use them. We're constantly criticized and defined by our bodies and our actions with our bodies.
And yet, for all that interest, for all those pronouncements, there's been so little interest in learning how our bodies actually work. This shit is so fucking frustrating. You'd think with so much definition as a social construct you'd see corresponding work defining the actual mechanics, or how the sexes really are different. But either there really isn't genuine interest beyond our body as a "thing" or we're an afterthought because as long as a man's body works or reacts or whathaveyou to what they're researching then it doesn't matter.
It's so belittling. I feel objectified every day, but learning about shit like this is when I feel the most objectified.
posted by barchan at 3:08 PM on June 30, 2015 [22 favorites]
And yet, for all that interest, for all those pronouncements, there's been so little interest in learning how our bodies actually work. This shit is so fucking frustrating. You'd think with so much definition as a social construct you'd see corresponding work defining the actual mechanics, or how the sexes really are different. But either there really isn't genuine interest beyond our body as a "thing" or we're an afterthought because as long as a man's body works or reacts or whathaveyou to what they're researching then it doesn't matter.
It's so belittling. I feel objectified every day, but learning about shit like this is when I feel the most objectified.
posted by barchan at 3:08 PM on June 30, 2015 [22 favorites]
Kisch mokusch, the article brings up the theory they don't use female mice because they don't want hormonal changes to affect the results. Which I don't understand myself since female humans have hormonal changes that could affect reactions, wouldn't that be worth knowing? But maybe hormone changes are different enough in mice and people, I have no idea.
posted by barchan at 3:16 PM on June 30, 2015 [1 favorite]
posted by barchan at 3:16 PM on June 30, 2015 [1 favorite]
don't respond as well to some pain medications
I think it's important to understand variance in both sexes and in individuals (pretty obvious of course). I'm not surprised that bias has existed and still exists. I've seen it myself many times with how doctors treat my girlfriends. Men and women should be regarded equally in terms of human rights, mental ability, etc., but their are some pretty significant differences biologically, despite the many similarities. I've always respected the changes in mood (broadly speaking) that the moon cycle can bring on (and of course that varies between individuals as well) but came to actually really appreciate it when my synthroid medication made me incredibly anxious over the smallest things until that side effect finally reduced itself in time (pretty mild and manageable now). It led to an interesting conversation with my sisters about how they'll ask themselves why they feel so low and depressed before recalling oh yeah, moon cycle (our family calls it that for some reason I can't recall).
That said, pain medication seldom works for me at the recommended doses. The last time I had surgery (with a local) I was screaming in pain but they refused to give me more anesthetic. Even morphine at regular doses was pretty much useless. I've read about the red head thing and brought it up (not really knowing if it's true or not since debate in the medical community seems to be all over the place on the issue) but only once was I listened to and surprise surprise, it worked.
I think we've all seen different people react to medication differently then we do ourselves. I've had people amazed how certain drugs don't knock me out like it does them. Some stuff works just fine, thankfully and most important for me personally, the dentist is not a nightmare for me. I do know people who have taken SSRIs without it making them feel like sleeping constantly, which they did to me.
I understand that, particularly with opiates, there is a dependency risk but I wonder if "illegal" solutions are being researched, i.e. "medical" pot, hallucinogenics for addiction and depression, etc. I saw something on cluster headaches where a guy grew his own magic mushrooms and consumed them once a month, which stopped the cluster headaches entirely. He and his family (being in the States) were scared shitless they'd be caught by the authorities and thrown in jail for years because of it (I do not know if this was actually a possibility). Perhaps they were more scared at the idea of a SWAT team smashing into their home, shooting their dog dead, and screaming at them like they were a massive danger to society at large.
I know a woman who was prescribed benzos, fully legally of course, when she was a teenager and now not a single doctor will treat her to help her get off them, and none of them will believe what she says or even listen to what she says, much less read anything I've printed out for them about others with same experience. It's sad when people have to go to the street to get what they need because going to street opens you up to a whole other level of unpleasant bullshit but dependency and pain can be so overwhelming it often becomes the only option.
There can be a lot of consequences that are not particularly thought out when research has bias or is not thorough. Marry that with policy that is seemingly absolute and it can lead to disaster.
From the article:
Previous studies led by pain expert, Jeffrey Mogil from McGill University in the US,
There's a McGill University in the States?
posted by juiceCake at 3:26 PM on June 30, 2015 [1 favorite]
I think it's important to understand variance in both sexes and in individuals (pretty obvious of course). I'm not surprised that bias has existed and still exists. I've seen it myself many times with how doctors treat my girlfriends. Men and women should be regarded equally in terms of human rights, mental ability, etc., but their are some pretty significant differences biologically, despite the many similarities. I've always respected the changes in mood (broadly speaking) that the moon cycle can bring on (and of course that varies between individuals as well) but came to actually really appreciate it when my synthroid medication made me incredibly anxious over the smallest things until that side effect finally reduced itself in time (pretty mild and manageable now). It led to an interesting conversation with my sisters about how they'll ask themselves why they feel so low and depressed before recalling oh yeah, moon cycle (our family calls it that for some reason I can't recall).
That said, pain medication seldom works for me at the recommended doses. The last time I had surgery (with a local) I was screaming in pain but they refused to give me more anesthetic. Even morphine at regular doses was pretty much useless. I've read about the red head thing and brought it up (not really knowing if it's true or not since debate in the medical community seems to be all over the place on the issue) but only once was I listened to and surprise surprise, it worked.
I think we've all seen different people react to medication differently then we do ourselves. I've had people amazed how certain drugs don't knock me out like it does them. Some stuff works just fine, thankfully and most important for me personally, the dentist is not a nightmare for me. I do know people who have taken SSRIs without it making them feel like sleeping constantly, which they did to me.
I understand that, particularly with opiates, there is a dependency risk but I wonder if "illegal" solutions are being researched, i.e. "medical" pot, hallucinogenics for addiction and depression, etc. I saw something on cluster headaches where a guy grew his own magic mushrooms and consumed them once a month, which stopped the cluster headaches entirely. He and his family (being in the States) were scared shitless they'd be caught by the authorities and thrown in jail for years because of it (I do not know if this was actually a possibility). Perhaps they were more scared at the idea of a SWAT team smashing into their home, shooting their dog dead, and screaming at them like they were a massive danger to society at large.
I know a woman who was prescribed benzos, fully legally of course, when she was a teenager and now not a single doctor will treat her to help her get off them, and none of them will believe what she says or even listen to what she says, much less read anything I've printed out for them about others with same experience. It's sad when people have to go to the street to get what they need because going to street opens you up to a whole other level of unpleasant bullshit but dependency and pain can be so overwhelming it often becomes the only option.
There can be a lot of consequences that are not particularly thought out when research has bias or is not thorough. Marry that with policy that is seemingly absolute and it can lead to disaster.
From the article:
Previous studies led by pain expert, Jeffrey Mogil from McGill University in the US,
There's a McGill University in the States?
posted by juiceCake at 3:26 PM on June 30, 2015 [1 favorite]
... the article brings up the theory they don't use female mice because they don't want hormonal changes to affect the results. Which I don't understand myself since female humans have hormonal changes that could affect reactions, wouldn't that be worth knowing?
Yes, but that's exactly the reason researchers used to give for not using human women in drug trials, that controlling for menstrual cycle hormonal variables was too complicated.
posted by jaguar at 3:37 PM on June 30, 2015 [2 favorites]
Yes, but that's exactly the reason researchers used to give for not using human women in drug trials, that controlling for menstrual cycle hormonal variables was too complicated.
posted by jaguar at 3:37 PM on June 30, 2015 [2 favorites]
MS research has been using female mice almost exclusively since they are more likely to get worse symptoms than male mice when a MS-type disease is induced. But during a recent study, a new lymphoid cell of interest was identified when, whoops:
"...the research team found that a graduate student had used male mice for each group instead of female mice. ... The researchers found that the genetic mutation triggered a different reaction in male and female mice."
Good news for further MS research. Bad news if you are a male lab mouse.
posted by mephisjo at 4:32 PM on June 30, 2015 [3 favorites]
"...the research team found that a graduate student had used male mice for each group instead of female mice. ... The researchers found that the genetic mutation triggered a different reaction in male and female mice."
Good news for further MS research. Bad news if you are a male lab mouse.
posted by mephisjo at 4:32 PM on June 30, 2015 [3 favorites]
Bizarre. So female but not male SCID sufferers should be more resistant mechanical pain hypersensitivity. And female patients, but not male patients, would likely experience less pain after organ transplant, since the immunosuppressive agents work particularly well on T cells. I cannot fathom why such a pathway would evolve with such sexual dimorphism.
I wish the articles had gone into more detail about this, but as I read them, the researchers used male and female mice that were hypersensitive to pain, and by blocking a certain aspect of microglial function in males and removing T cells in females, were able to reduce that hypersensitivity to "normal."
But an article in The Verge (not linked in the FPP, but linked in the ScienceAlert link) said that, without their T cells the female mice fell back on the microglial system used by the males
And it's interesting you would bring up organ transplants, because I've been wondering whether, in adult female recipients, you could induce host tolerance by causing the host to react immunologically to the organ graft as if it were a fetus, instead of suppressing the immune response altogether, because women's immune systems are set up to accept rather than reject a fetus -- and given how painful pregnancy and delivery can be, it doesn't seem beyond the range of possibility to me that the specific T cell populations which play a part in inducing tolerance of the fetus would also be involved in mediating pain in females.
posted by jamjam at 5:00 PM on June 30, 2015 [1 favorite]
I wish the articles had gone into more detail about this, but as I read them, the researchers used male and female mice that were hypersensitive to pain, and by blocking a certain aspect of microglial function in males and removing T cells in females, were able to reduce that hypersensitivity to "normal."
But an article in The Verge (not linked in the FPP, but linked in the ScienceAlert link) said that, without their T cells the female mice fell back on the microglial system used by the males
So what exactly do female mice use instead of microglia? Mogil and his team suspect that a different kind of immune cell, called a T cell, may be involved instead. To test this idea, the researchers removed T cells from female mice. They found that under those conditions, female mice adapt and use the male microglial pain system. But when the researchers gave them their T cells back, the female mice stopped using the microglia. Still, exactly how T cells are involved in the pain experienced by female mice is anybody's guess.I bet you're right though, to imply that both the microglial system and the T cell system also have a function of suppressing pain in some circumstances.
And it's interesting you would bring up organ transplants, because I've been wondering whether, in adult female recipients, you could induce host tolerance by causing the host to react immunologically to the organ graft as if it were a fetus, instead of suppressing the immune response altogether, because women's immune systems are set up to accept rather than reject a fetus -- and given how painful pregnancy and delivery can be, it doesn't seem beyond the range of possibility to me that the specific T cell populations which play a part in inducing tolerance of the fetus would also be involved in mediating pain in females.
posted by jamjam at 5:00 PM on June 30, 2015 [1 favorite]
Hmm, rereading your comment, I see that you did not imply a pain suppressing function.
posted by jamjam at 5:07 PM on June 30, 2015
posted by jamjam at 5:07 PM on June 30, 2015
Being a red-headed man means getting a tiny window into how much this shit sucks
Get your head scanned. It may be that your nerves are not where they are on most people. It took a long time for someone I know to get that figured out.
posted by Mr. Yuck at 5:20 PM on June 30, 2015
Get your head scanned. It may be that your nerves are not where they are on most people. It took a long time for someone I know to get that figured out.
posted by Mr. Yuck at 5:20 PM on June 30, 2015
So it looks like last year, the NIH moved to require gender parity in drug studies using animals and animal tissue in NIH funded research. The worst part about googling this was finding people that disagreed because it would be hard. Thanks, male scientist!
As a chronic pain sufferer who's not adequately treat, and has talked to far too many women who've been down the same, shitty path that I have, the idea that both no one really considered (or cared) about the differences women experience and that there are people still fighting it is beyond rage inducing.
posted by [insert clever name here] at 6:34 PM on June 30, 2015 [2 favorites]
As a chronic pain sufferer who's not adequately treat, and has talked to far too many women who've been down the same, shitty path that I have, the idea that both no one really considered (or cared) about the differences women experience and that there are people still fighting it is beyond rage inducing.
posted by [insert clever name here] at 6:34 PM on June 30, 2015 [2 favorites]
Get your head scanned. It may be that your nerves are not where they are on most people. It took a long time for someone I know to get that figured out.
I am not redheaded, but whenever I am at the dentist and they want to do a nerve block, it turns into a farce of repeated injections because my nerves are evidently not in the correct places.
posted by Dip Flash at 7:29 PM on June 30, 2015
I am not redheaded, but whenever I am at the dentist and they want to do a nerve block, it turns into a farce of repeated injections because my nerves are evidently not in the correct places.
posted by Dip Flash at 7:29 PM on June 30, 2015
"but how can the SCIENTIFIC METHOD be sexist"
yeah, the scientific method I learned and learned to have faith in should control for things like
Nothing screws up an experiment faster than a massive skin wound that arises because the mouse vendor has not included the dominant male in your cage and the mice have fought to re-establish dominance.
wait, holy fuck, that scientific method as actually employed is at the mercy of mouse vendors?!??
posted by 7segment at 1:43 AM on July 1, 2015 [1 favorite]
yeah, the scientific method I learned and learned to have faith in should control for things like
Nothing screws up an experiment faster than a massive skin wound that arises because the mouse vendor has not included the dominant male in your cage and the mice have fought to re-establish dominance.
wait, holy fuck, that scientific method as actually employed is at the mercy of mouse vendors?!??
posted by 7segment at 1:43 AM on July 1, 2015 [1 favorite]
Kisch mokusch, the article brings up the theory they don't use female mice because they don't want hormonal changes to affect the results.
Thank barchan, I read it quite quickly and evidently missed that part. Sounds like of those things that are done for 'historical reasons', which is usually ground in some not-unreasonable-for-the-time-but-nevertheless-not-properly-tested theory that dates back over 20-30 years. You actually see a lot of that in research, and its quite simplistic/myopic. If you're not thinking about all the other factors, it's easy to develop a mindset that one approach is less variable than another. I mean, one could easily argue that the behavioural variance of mice based on their pecking order is more pronounced in boys than girls, and therefore one should be preferentially using female mice.
The reality is that there are lots of variables that play a potentially important role that we have very little idea about, or are not looking for.
Hmm, rereading your comment, I see that you did not imply a pain suppressing function.
No, I didn't, but I get where you're coming from. Regulatory T cells (Treg) can be expected to suppress conventional T cells, which means that Treg may suppress pain pathways. We know that Treg are elevated in pregnancy, where they seem to play an important role in reducing the risk of pre-eclampsia. So it's entirely possible that this pathway evolved so that it could be suppressed by Treg during pregnancy. There might be a potential grant application in that idea!
wait, holy fuck, that scientific method as actually employed is at the mercy of mouse vendors?!??
Oh you have no idea. You make the order and then a little black rodent arrives in a box and you trust that that mouse is what you've asked for. There are plenty of very different mice (genetic knockouts etc.) that will look indistinguishable from that little C57BL/6 you ordered. And it's not like they don't make mistakes. I remember a while back a lab next door to ours was getting all of these rejection issues with their mice because the vendor had managed to mix up the genetics.
And don't even get me started on genetic drift!
posted by kisch mokusch at 4:44 AM on July 1, 2015 [2 favorites]
Thank barchan, I read it quite quickly and evidently missed that part. Sounds like of those things that are done for 'historical reasons', which is usually ground in some not-unreasonable-for-the-time-but-nevertheless-not-properly-tested theory that dates back over 20-30 years. You actually see a lot of that in research, and its quite simplistic/myopic. If you're not thinking about all the other factors, it's easy to develop a mindset that one approach is less variable than another. I mean, one could easily argue that the behavioural variance of mice based on their pecking order is more pronounced in boys than girls, and therefore one should be preferentially using female mice.
The reality is that there are lots of variables that play a potentially important role that we have very little idea about, or are not looking for.
Hmm, rereading your comment, I see that you did not imply a pain suppressing function.
No, I didn't, but I get where you're coming from. Regulatory T cells (Treg) can be expected to suppress conventional T cells, which means that Treg may suppress pain pathways. We know that Treg are elevated in pregnancy, where they seem to play an important role in reducing the risk of pre-eclampsia. So it's entirely possible that this pathway evolved so that it could be suppressed by Treg during pregnancy. There might be a potential grant application in that idea!
wait, holy fuck, that scientific method as actually employed is at the mercy of mouse vendors?!??
Oh you have no idea. You make the order and then a little black rodent arrives in a box and you trust that that mouse is what you've asked for. There are plenty of very different mice (genetic knockouts etc.) that will look indistinguishable from that little C57BL/6 you ordered. And it's not like they don't make mistakes. I remember a while back a lab next door to ours was getting all of these rejection issues with their mice because the vendor had managed to mix up the genetics.
And don't even get me started on genetic drift!
posted by kisch mokusch at 4:44 AM on July 1, 2015 [2 favorites]
When you think about it, an entirely different chromosome should have a marked affect on much more than reproductive systems. And then there's the recombinant X or Y chromosomes to consider too, which ties into what DrMew talked about in another thread; hopefully there's more research into that.
But ugh, banning women from drug safety tests until the 90's, and all this ignoring of gender, sounds really frustrating.
posted by halifix at 2:20 PM on July 1, 2015
But ugh, banning women from drug safety tests until the 90's, and all this ignoring of gender, sounds really frustrating.
posted by halifix at 2:20 PM on July 1, 2015
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