不同性别，痛起来不一样？| Nature Podcast

来源：Nature自然科研

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Interviewer: Shamini Bundell

There’s a feature in this week’s Nature about how there could be different pain pathways in males and females, with various studies that have looked at certain types of pain in both humans and rodents. The journalist who wrote and researched the feature is Amber Dance, so I called her up and asked her whether people experience pain differently depending on their biological sex. 

Interviewee: Amber Dance

The thing is, pain is subjective. If I punch you in the arm and you punch me in the arm, we have no idea who hurts more. If we had to rate it on a scale of one to ten, and I said my pain is a two and you said yours is a three, well what does that mean? There does seem to be indications that women are more sensitive to pain, but the scientists I spoke with said that’s not really the interesting question. The interesting question is what is happening under the skin to create pain conditions, and that their finding is in some cases – not all but some cases – quite different between the sexes, and that’s what has real implications for treatment and clinical studies. 

Interviewer: Shamini Bundell

Okay, so let’s say I’m fighting with my younger brother, not that I’d ever do that. I hit him, he hits me, we both go ‘ow’, we could actually be having different physiological physical responses to that pain? 

Interviewee: Amber Dance

Right, right, now, I suspect being punched in the arm by a sibling is probably going to use the same pathways. A lot of the scientists that I talked to, what they’re working on is issues more of chronic pain or when you have pain caused by damage or problems with the nervous system that interprets pain. 

Interviewer: Shamini Bundell

And when researching basic mechanisms, a lot of the experiments are done with rodents rather than actual people, so how did researchers first start investigating whether chronic pain and things like that, there might be sex differences going on with that? 

Interviewee: Amber Dance

Very few researchers were for quite a while. There was just this assumption, well, in mice and rats it’s going to be the same and gosh, it’s so much easier to work with males because they don’t have an oestrous cycle and we don’t have to worry about any hormonal fluctuations, so let’s just look at males and assume it’s the same. That turns out to be a poor assumption because actually males have hormonal fluctuations in testosterone too. The big change has been that the grant funding agencies are starting to say – across biology and not just pain – that you have to consider sex as a biological variable. And so that has kind of pushed more scientists to go, alright, I’ll check in females and sometimes they go wait, it’s different. 

Interviewer: Shamini Bundell

And I guess if you’re talking about medicine and testing things that you want to use on humans, that can be a big problem, right? 

Interviewee: Amber Dance

So, the implication is, let’s say you go and do all your drug development in male rodents, and then you go and do a clinical trial in half men, half women. If the drug only works in the men and it doesn’t work in the women and you just go and average all your results, you’ll say well that drug’s not very good, let’s not continue with it. So, it’s entirely possible that there have been pain drugs that have been considered failed in clinical trials in the past that might have worked for a subset of the sexes in those trials. 

Interviewer: Shamini Bundell

But to come back to the main question, how can such a basic thing as pain be so different? Surely we all have the same nerves and receptors and brains to some extent? What is the difference going on between sexes there? 

Interviewee: Amber Dance

Pain is closely tied with the immune system, so a lot of the differences people are seeing between sexes happen when immune cells are involved in the pain pathways and what people tend to point to as a hypothetical explanation is females get pregnant, which means you’ve got essentially a foreign organism in your body for some length of time and you need to not treat that as an invader. 

Interviewer: Shamini Bundell

And what kind of mechanisms are we talking about? How are immune cells involved in pain pathways? 

Interviewee: Amber Dance

So, one of the biggest papers in this field came out of Jeff Mogil’s lab in Canada. They were looking at a pain system in these mice, and it’s known that it involves a cell type called microglia, which is sort of the immune cells of the nervous system, and if you block the microglia then it should block the pain. And so, they did this in males and everything worked fine as expected, and then they tried it in females and nothing. No matter what you do to the microglia, it doesn’t block the pain response in females. And what they think is going on is that females don’t use microglia for the pain response – they use T cells instead. So, you have completely different cell types of the immune system contributing to what looks on the outside like the same pain. 

Interviewer: Shamini Bundell

And that’s such a major difference – a completely different type of cell. And then of course, that’s really important if you’re trying to target the cell or another part of the pathway to treat pain to know which one it is. But is it that simple? Is it a sort of binary where men have one type of mechanism for pain and women have another? 

Interviewee: Amber Dance

So, we know that you can’t just say there’s male and female and that’s it. It’s clear that some people fall somewhere in between. Most of the studies in rodents or in people have just looked at male and female. I did find one study from about 12 years ago where they looked at people who are undergoing gender transition through hormonal treatment, and they asked them about their pain experiences before and after starting the hormone treatment, and they did find that in people who are going from male to female, some people reported more pain after, versus people going from female to male sometimes reported less pain after the transition, suggesting again that hormones make a difference. 

Interviewer: Shamini Bundell

And then of course, different people will have different hormone levels naturally, so this also leads into this idea of personalised medicines as something that’s perhaps targeted to an individual even? 

Interviewee: Amber Dance

Right, so the eventual hope is that pain medications could be personalised or applied precisely to the person in pain based on what kind of pain they have, what kind of mechanisms are happening under the skin, how they’re experiencing it, genetics, all kinds of factors. In a way, sex is rather a blunt way to divide people, but it could be a start towards that kind of really precision medicine where you get the drug that’s going to work on your pain the first time.

Interviewer: Shamini Bundell

That was freelance science journalist Amber Dance. Her feature includes a lot more details of work by various groups, so do go check it out at nature.com/news. ⓝ

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