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.

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

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.

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.

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 🤷

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!

Using a dollar store’s AI to help with coding homework would be hilarious! Just like rocks on pizza.

You seem to be placing me in the wrong bucket. I use AI professionally, yes, but it also pisses me off pretty regularly. I’m not some “AI Bro” or whatever TF you’re thinking. Just some guy who finds AI mistakes to be funny and I want to reproduce them.

You check the links/references it gives you.

Gemini does a pretty good job of this because it doesn’t seem to have much built-in knowledge. Instead, it just searches the Internet on your behalf and returns summarized results with links to where it got that specific information.

I use it to search for scientific research all the time and the summaries often aren’t detailed enough so I actually click on those links. I’ve yet to encounter a situation where it fucked that up (invented links that don’t exist) but I have heard about it happening.

So far, the summaries have seemed to be pretty spot-on when it comes to biology papers 🤷

Uh… I was just curious because sometimes it’s fun to see how the LLMs screw up. e.g. rocks on pizza.

It’s not the lack of evidence presented, it’s the person that asked the question that’s the problem.

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.

Give us an example of some of the prompts you’re using and what LLMs. I’m curious if it’s a use case difference or you’re using the dollar store’s customer service AI to try to help you with your coding homework.

He claims heaven isn’t a place, it’s a person, and that he entered that person.

Now he’s reminded of heaven everywhere he looks. The trees, the mountains, etc.

(Rubs hands together) “Time to download more RAM!”

Trump administration ruins yet another chairished tradition.

Compared to slavery‽ Yeah… No.

Hey, if the shoe fits…

Since the hazing was interrupted, these poor dudes are going to have to attend ketchup classes.

So their “solution” is for senior developers to keep giving work to junior developers… In order to prevent senior developer salaries from skyrocketing.

It’s almost as if… for-profit healthcare is fundamentally broken somehow. 🤔

Oh yes, I remember. I remember that Google started to become worse and worse starting around 2018. By 2020, SEO was too damned good and ruined so much of the results. By 2024, trying to find technical info became so difficult I’d end up searching with DDG which was sometimes better.

All this was before AI slop existed.

Don’t blame AI. Blame SEO by commercial interests. They’ve been generating slop since the early 2000s. AI just makes them faster at it.