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
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 🤷
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
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:
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.
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.
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.
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
Doh! You’re right. I had to dig deep into my old notes about this and here’s the papers:
Edit: Almost forgot the studies showing female (mammals) switch to the male pathway during pregnancy:
…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 🤷
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:
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
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.
I’d rather call it cherry-picking.
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.