The pain of disparate impact or the disparate impact of pain?

From Why the sexes don’t feel pain the same way: After decades of assuming that pain processing is equivalent in all sexes, scientists are finding that different biological pathways can produce an ‘ouch!’. by Amber Dance. It is a pity that Amber Dance has to introduce a couple of social justice jibes into the article, particularly when the evidence submitted contradicts the jibes, but interesting none-the-less.

At McGill University in Montreal, Canada, Sorge was investigating how animals develop an extreme sensitivity to touch. To test for this response, Sorge poked the paws of mice using fine hairs, ones that wouldn’t ordinarily bother them. The males behaved as the scientific literature said they would: they yanked their paws back from even the finest of threads.

But females remained stoic to Sorge’s gentle pokes and prods. “It just didn’t work in the females,” recalls Sorge, now a behaviourist at the University of Alabama at Birmingham. “We couldn’t figure out why.” Sorge and his adviser at McGill University, pain researcher Jeffrey Mogil, would go on to determine that this kind of pain hypersensitivity results from remarkably different pathways in male and female mice, with distinct immune-cell types contributing to discomfort.

The science is never settled.

Chessel, at AstraZeneca, would be happy to develop a pain drug that works only in people of a certain sex. But the sex of study participants and animal subjects is driven by practicality, ethical concerns and government regulations, he says. AstraZeneca uses female rodents in most of its preclinical pain research because they’re less aggressive and easier to house and handle than males. In early clinical trials, safety is the focus, so companies often exclude people who could become pregnant. As a result, drugs are mostly trialled on men and on women who are past menopause.

Even if scientists develop drugs that are targeted to male- or female-specific pain pathways, these might not be enough. It might be best to customize drugs more closely, to take into account the spectrum of genetics, hormone levels and anatomical development.

A further factor is surely cost. It is, as a general principle, highly advantageous to assume biological universalism without obvious reason to do otherwise. It is cheaper to run a one hundred person study that is 50% male and 50% female under the assumption that the biological response is going to be identical than it is to run a 200 person study, 50% male and 50% female, because you assume a priori in advance that all human systems must differ because of sex.

The cost of running more and more discrete studies (sex, orientation, age, weight, etc.) goes higher and higher with less and less certainty about the potential for benefit.

It will be interesting to see where this leads.

Pain responses also seem to change throughout life, around the time hormone levels rise or fall. Studies looking only at biological sex have found that, at puberty, the rates of pain conditions rise more in girls than in boys. And as people age, and some hit menopause, hormonal levels change again, and sex differences in chronic pain rates begin to disappear. Pregnancy changes pain responses, too. Mogil’s group reported in 2017 that, early in pregnancy, mice switch from a typically female, microglia-independent mechanism of pain sensitization to a more male-associated one that involves microglia. By late pregnancy, the animals don’t seem to feel chronic pain at all.