Ugh, Mondays…

Well I assume women feel more pain in general considering they have periods which are accompanied by pain and other unpleasant sensations. It's probably one of the reasons women have on average higher pain tolerance than men.

Well, yeah: Women use T cells to communicate pain through the neuro-immune pathways while men use microglia-to-BDNF (Brain-Derived Neurotrophic Factor). The women's version of pain completely bypasses all of that, jumping straight to pro-inflammatory cytokines that increase sensitivity.

Unless the woman is pregnant. Then she'll use the same exact pain pathways as men. Presumably, to make the pain of childbirth not-as-bad.

Self-reported study

I'm stepping far outside my area of expertise here so please treat this as good faith, uneducated questions.

My understanding is that most of this research is about chronic pain rather than acute pain. I know AFAB people experience chronic pain at like 3x the rates of AMAB people, and that especially immune-moderated pain diseases are much harder to manage in AFAB. I also recognize this is an area of active research and much is yet to be confirmed, but I wonder if acute pain pathways are the same as chronic pain pathways? My limited understanding is that acute pain from tissue damage, etc. is still understood to be nervous system activation for both sexes.

Is it also accurate that these pathways and their activations are largely sex-hormone related? I wonder if that means we could survey trans folks on their experiences of pain before and after transition, both ways.

Thank you for your comment, this has spurred me to do some reading!

Also just as I read about this on pubmed because I find this to be very interesting, I find myself angry at how much of this incredibly valuable research has/will be defended by various right wing governments as "woke". One of these papers by the International Association for the Study of Pain discusses how various hormones may conditionally amplify or suppress pain depending on various factors, rather than a blanket "estrogen amplifies pain" and I just think that's really fascinating. The body is so complex.

This is an aggregate article I found from IASP that links to some of the studies I found: https://www.iasp-pain.org/resources/fact-sheets/biological-mechanisms-underlying-sex-differences-in-pain/

Really interesting stuff. I suffered from some chronic pain for what felt like forever this past year and so I had done some "basic" reading, but I didn't bother to go much further beyond what I needed/wanted at the time. This is cool.

We don't have sensors that can detect pain like we can detect heart rate or anything, so yeah it's going to be self-reported

Can you provide a source for this? I'm not a bio expert but this seems not right to me. I would love to be proven wrong and learn more though.

Right but isn't this susceptible to the "is my green your green" qualia problem? The proper conclusion should be that women experience more pain OR are more likely to report their pain as higher. I feel like the former is more likely but how could you tell?

Which means the only thing the study concludes is that women report feeling pain more often than men.

Which is fine, it just doesn't have anything to do with who feels more pain, but more studies on the culture around pain reporting between the genders around more objective markers could lead to very useful information

Anecdotal, but given how many trans women i know who have developed some form of chronic fuckery or another, i'd believe the hormone drivers. Fascinating things

Oh geeze, I'm not an expert in this stuff. I'm writing a novel about a PhD-level biologist (who becomes a shapeshifter) and ended up doing loads of research about biology... stuff in order to make the way he modifies people a bit more believable (so many stories are so full of hand waving these days it drives me nuts!).

One of the things I ended up researching was sexual dimorphism in various species including humans and wow what a rabbit hole that is! I have in my notes all sorts of things (differences) that most people have no clue about:

• Women have different livers. Specifically, estrogen/testosterone turns on/off epigenetic pathways that make their livers behave a bit differently. So if a woman receives a liver transplant from a man or vice versa, it'll be a while before it starts behaving "on brand" haha.
• Women's hearts are bigger/stronger/thicker but most people know that (necessary for pumping blood for more than one!)
• Women's internal organs can move around a lot more than men's. They're not fixed in place like with men. Along these lines, women's tailbones can move a little bit (men's might as well be hard stone). This was important research because my shapeshifter character gets requests to give people tails and I needed to know if that was even possible and, come to find out, much simpler to give women tails than men! Haha
• The tendency for women's brains to form more cross-hemisphere connections VS men's tendency to form front-to-back connections is actually a very funny part of the story (it's a comedy). Anyone that reads that part (and doesn't understand what it means yet) is going to be thinking, "holy shit that makes so much sense!" Hahaha
• Women can perceive textures men cannot. The reasons why aren't complicated: Thinner skin, smaller fingers means greater nerve density and sensitivity. This was the research that had me looking into nerve pathways and why women are just generally more sensitive than men. Besides what I already mentioned, women store fat completely differently than men. Essentially, men and women have completely different flesh. Men cross-link fat cells making them much more "solid" whereas women stack their fat cells on top of each other like little pillows... This is why they're softer than men.
• Now combine the flesh knowledge with the T-cell nervous response and the fact that stacked fat cells (and the vasculature that goes with that) together and you end up with this: Women bruise much easier than men. Bruising results in a cytokine (swelling) response... Which amplifies pain in the affected region. Having more lifelong exposure to cytokine in various joints that are constantly being used/bumped, it makes sense to me that women would be more susceptible to inflammation-related pain disorders such as rheumatoid arthritis. Which impacts women at two to three times the rate of men!

Hopefully that explains what I think I understand about the differences that lead up to women experiencing pain differently/more intensely.

...and that's just scratching the surface of all the differences! People think men and women "are basically the same, just with a few physical differences" but it's more like this: Men and women experience the world completely differently from each other.

Women physically see things differently than men (they see colors in greater resolution), they feel the world differently from men, and they have 50% more olfactory bulb neurons than men which means they have much more sensitive noses (especially to certain compounds like sulfur and scents like lavender have a vastly enhanced effect!).

Women live in a different world than men. We need to stop pretending we're the same and start accounting for it in medical studies!

Yeah and headlines like this come out, then suddenly when I (as a man) mention having chronic pain, people will hit me with the "but studies say that women feel more pain than men!"

Yeah, well that doesn't make my pain go away. But I suppose that's just a non-falsifiable anecdote, so the proper academic perspective is that my subjective experience of pain is empirically unsound.

How that differs in any way from the study participants' experience of pain is anybody's guess, but I suppose it's easier to get research funding if you make your study sound feminist so...

This is fascinating and the way you plan to weave science-fact into science-fiction reminds me a lot of Crichton.

While this comment is very well written, I believe the reason you're not getting a lot of upvotes compared to the other guy is because you didn't cite a paper, which was the original request.

This sent me on an hour-long scour of a variety of papers, and it ended with me finding one titled "Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain" by Dedek et al.

In this paper, they take spinal samples from deceased humans and mice and compared sex differences after they doused them in BDNF. They found that the pathway responsible for uptaking BDNF was only active in male samples.

I think you're extrapolating a little if you're saying, based on this, that men solely use this pathway for pain and women don't, but then again, I can't tell what paper you're looking at because you never posted it.

TL;DR: what you're saying about BDNF might be true, but please post sources when making specific claims like that, especially when asked :3

PS your book sounds really interesting

Women have lower pain tolerances though, with the exception of when they are in labor (due to very elevated hormone levels)

Recent experiences would make me believe the pain tolerance is not higher in labor.

When's the book coming out?

One, source? Two, wouldn’t a lower pain tolerance only illustrate the point women experience more pain? If women’s pain tolerance is lower that means the pain we experience is worse/more… so either way really… women experience more pain in general.

And sometimes "the best possible" still isn't enough to support any kind of conclusion.

it's bullshit. that's why I downvoted it. agreed, it's well-written, but it's bullshit none the less, and they are basically fictionalizing the results of the study for their own ends and passing it alone as if it's factual reality, when it isn't. most of it is fictionalized re-enforcement of sexist stereotypes.

it's false information presented as authoritative truth, that has no basis in medical reality, and articulates a lot of magical thinking nonsense. they are pushing a magical thesis and found some study that vaguely supports their magical thinking and are presenting it as some profound truth.

a lot of science writing and reporting suffers from the author getting high on their own supply of verbiage, and often straight up contradicts the study they are reporting on to make it sound more dramatic and profound and meaningful for a lay audience.

and the lay audiences eat it up. CERN is going to cause a blackhole and destroy the planet!, etc.

but people like hearing nice sounding magical nonsense rather than they like bearing boring facts of biology where the differences between men and women he's citing are entirely trivial.

further there are way bigger factors at play in pain perception than sex, like your genetics, but talking about the COMT (Catechol-O-methyltransferase) gene differences in people influences how they perceive pain isn't as 'sexy' as claiming being born with a vagina gives you magical pain perception powers.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3690315/ - postoperative for the same procedures, women rate their pain as higher. I would interpret that to mean they have lower pain tolerance, although as the article acknowledges, its tricky to measure.

Well, sure, I agree, it is probably why women experience more pain, as opposed to they have more painful diseases/injuries.

https://sarahbuckley.com/pain-in-labour-your-hormones-are-your-helpers-2/

Certainly not trying to say labor isnt painful though!

Look, I’m a male doctor and female pain isn’t real. They just complain too much.

Men in the other hand need real support and medication get through their obvious extreme pain.

/s

Doh! You're right. I had to dig deep into my old notes about this and here's the papers:

• https://doi.org/10.1038/nn.4053 (the most cited one, foundational for the sex differences in pain pathways)
• https://doi.org/10.7554/elife.69056 (follow up study that looked at how T cells modulate the dimorphism)
• https://doi.org/10.1097/j.pain.0000000000002215 (most recent study I could find)
• https://doi.org/10.3390/ijms19010281 (more of an "also relevant" paper)

Edit: Almost forgot the studies showing female (mammals) switch to the male pathway during pregnancy:

• https://pubmed.ncbi.nlm.nih.gov/28877966/

...and this study indicates that humans have the same genes associated with this sexual dimorphism:

https://pmc.ncbi.nlm.nih.gov/articles/PMC10169414/?hl=en-US

Since it's highly unethical to test pain pathways in humans, we have to rely on the mouse studies and extrapolate from there. The RNA testing shows we have the exact same genes as mice for pain expression, so the evidence lines up that men and women are using these different pathways for pain.

I didn't just use "magical thinking" like I've of the other commenters suggested 🤷

It'll be a while. I'm going to use it as the poster child for a new web novel publishing site I'm building.

I've already got much of the code written for the site, but I had to stop because I was thinking, "I should really write a story using all these features first so I know what works and what doesn't."

...and that's the phase I'm currently at.

I have a draft written for the first two acts, so it won't be forever but probably at least six months out.

Is there a functional difference between 'lower pain tolerance' and 'experiences more pain'?

Your comment makes me feel like I've missed something here

For my sources, see this comment: https://programming.dev/post/57533861/26373477

If your genetics plays an important factor in pain, consider that your sex is "your genetics", TubularTittyFrog.

you can't.

unless there is like some standard phenomena you could measure, like electrical activity in the brain corresponding to pain. but that doesn't necessary translate to people's perception of pain, it would just be a measurement of activity in their brain during pain stimulus.

further, pain comes in so many types, varieties, and time frames. it's very diverse. sometimes a lower amount of pain is worse, if it's more universally distributed or like throbbing, than a singular acute sharp sensations, etc.

but all i can say is I've been hospitalized multiple time and the medical staff have been repeatedly shocked I'm not reporting anything other than mild discomfort and have accused me of underreporting pain.

Almost forgot: I posted my sources in this comment: https://programming.dev/post/57533861/26373477

it’s false information presented as authoritative truth

I'd rather call it cherry-picking.

I would argue that, no, there isn't, hence why I was confused by the person i was originally replying to who said that women have a higher pain tolerance on an article that said women experience more pain.

Remind me when its out

Maybe they just whine more?
::: spoiler ...
This is totally a joke

Okay, let's go through these:

https://doi.org/10.1038/nn.4053
Yep, it shows that male mice are able to recover from induced mechanical hypersensitivity, while female mice were not. They hypothesised that this is due to the female mice getting around this by using adaptive immune cells, meaning this pathway still had the mechanical hypersensitivity, despite the original incision being healed. It is to be noted that, in the absence of adaptive immune cells, female mice did seem to use the standard glial-dependent pain pathway.
While this does show that female mice may recover from neuronal injury poorly, it doesn't show that female mice experience more pain than male mice at a baseline. Similarly, this wasn't done in humans and thus comparison becomes very hearsay, although it is to be noted that these mice have very similar neural structures to humans and that human research in this area is usually very sparse.

https://doi.org/10.7554/elife.69056
Very interesting study. Weirdly, by showing female mice inhibiting microglia-induced pain hypersensitivity with T-cells, it would imply that female mice have the capacity to reduce pain more so than male mice.

I unfortunately don't have time to go over the others, but from those two it wouldn't be without reason you could say that women likely use different pathways to signal pain compared to men, althoughyou can't say that with anywhere close to certainty, as this wasn't done in humans, nor was that the point of the papers.
In a sci-fi context it'd make perfect sense to present these findings as absolute in a JoJo sort of way, but I'd warn not to present these as factual as you did in the original comment. In a book, a disclaimer at the start would honestly let you run loose in what you say on these topics, and open the gates as to what you could get away with.

TL;DR the people handwaving these findings are wrong, but you shouldn't take these studies as absolute in a human context

Sure!

Disclaimer: This LitRPG comedy about a shapeshifter is a work of fiction. 😇👍

Possibly interesting: The following placebo-controlled clinical trials were for drugs that inhibited the microglial pathways (via p38 MAPK inhibitors and minocycline). They all failed:

• https://pubmed.ncbi.nlm.nih.gov/21576029/
• https://pubmed.ncbi.nlm.nih.gov/23239139/
• https://pubmed.ncbi.nlm.nih.gov/25751578/
• https://pubmed.ncbi.nlm.nih.gov/25569640/

There's a problem with all of them: They failed to disaggregate results based on sex, which is exactly the problem I was talking about when I said "(we) need to account for (sex in medical studies)" earlier. This leads me to believe that these pain medications could have been useful for men, but probably not for women if the mouse studies indicating different pain pathways for each sex apply to humans.

There's a whole article about this: https://doi.org/10.3389/fneur.2025.1730291

Historically, research has assumed a largely “sex-neutral” model of pain. Yet mounting evidence demonstrates that men and women differ substantially in pain perception, processing, and response to treatment (7–9). These differences span the entire biopsychosocial spectrum, including neural circuitry, immune function, hormonal regulation, genetics, and social context (10). Understanding these distinctions is critical, as failure to account for sex as a biological variable risks overlooking mechanisms unique to half of the population and may lead to suboptimal or even harmful therapeutic approaches.

I also find it interesting that in ultra endurance events, the gap between male/female performance disappears, and seems to favour women. I wondered if pain tolerance comes into it or use just physiological.

My wife and i got matching tattoos. I almost ripped the hand grips of the table and we had to wipe the drool up from where she feel asleep.

We aren't built the same lol

Ages ago I'd read something like "women have a lower threshold before they start feeling pain, but a higher overall pain tolerance as compared to men". I.e. they feel pain earlier than a man might under similar conditions, but are able to cope with higher pain levels better. At that same time there seemed to be wide agreement that pain was poorly understood. Surely a lot of good work on the study of pain has been done that I am not aware of in the intervening time.

it's because what matters is vo2max.

men have higher vo2max, but also higher mass, so in the end the supply of oxygen is the same.

it has nothing to do with pain. it's about your bodies ability to power itself, and that overwhelmingly comes from oxygen uptake.

that and how many carb you can uptake, which is proportional to your mass.

lol women literally deal with an entire week of pain every week for decades. So, yea. Women do feel more pain and so we have a higher pain tolerance from being told to suck it up and work at a higher level than men.

You think vo2 max is important for ultra endurance? I would say mitochondrial efficiency is more important in anything above say 12 hours.

Well the mitochondria are the powerhouse of the cell.

The actual title of the study is Global and regional reference curves for pain across the lifespan in 6.1 million individuals in 118 countries.

Which makes sense, given its contents. The study is fine. The Guardian's article's title is unscientific sensationalist trash, imho.

There's also a masculinity component, will men even log minor pain or is it so ingrained that pain needs to reach a certain threshold to count?

It's tough to say, I'd be interesting to see this done across cultures to see if when properly controlled some cultures have more pain in men. More study needed.

Exactly, those kinds of things are much more intersting

I just read this and the other comment you left! Thanks for sharing, it was super interesting! Biology is so cool. I love learning more and appreciate the info and sources ❤️

you need oxygen to create energy.

there is no such thing as anaerobic endurance. it's aerobic.

VO2 max is a measure of how much oxygen you can use at max effort. Ultra endurance has little to do with this metric.

(Dw I never read your sports studies grade 1 response to this)

VO2 max is the maximum volume of oxygen your body can consume, transport, and use per kilogram of body weight during intense, maximal exercise, expressed in mL/kg/min. It serves as a primary marker of cardiorespiratory fitness, endurance capacity, and long-term health.

But please tell me more how it's not related to endurance at all or something. Or is the Mayo Clinic wrong too? It is measured at max effort, but it's a measurement of how much oxygen your body can use generally.

ultra endurance athletes typically have VO2Maxes in the 60 or above range. they don't have ones in the 30-40 range.

the higher your vo2max, the better endurance you have for any aerobic activity, because as you increase you vo2max, you increase your ability to process oxygen generally. it's also an adaptive metric, it's not innate. You get a higher vo2max by training and you get better endurance by doing maximal efforts that enhance your cardio fitness.

Where Vo2Max doesn't matter is for anaerobic activity, where your body isn't processing oxygen for fuel. Like power lifting.

It's also why blood doping works, because enhance your red cell count and therefore your vo2max. it doesn't enhance your mitochondrial efficiency at all.

you need both, hence why endurance athletes need maximal effort training and they can't just run at zone 2 forever and expect to get better.