Pain on the Brain


Men and women experience pain in different ways, a new study shows.

"Aaaagh, my KORs are killing me!"

The behavior of opioids – chemicals that suppress pain – differs between men’s and women’s bodies. This is because the three main types of opioid receptors in the brain and spinal cord interact very differently, depending on whether their owner is a man or a woman.

See, scientists have known for years that certain kinds of narcotic analgesics – a certain class of pain relieving drugs – are much more effective on women then on men. It was hard to understand why, though, because both men and women have mu (MOR), delta (DOR), and kappa (KOR) opiate receptors – the three main kinds – and these receptors work in essentially the same way in either gender.

But now, scientists have found that the spinal cords of female animals have almost five times as many kappa-mu heterodimers – complex molecules formed by combining KORs and MORs (commonly called KOR/MOR heterodimers) – as those of males. And not only that – the number of KOR/MOR heterodimers climbs four times higher when a woman’s body is pumping with estrogen and progesterone – two hormones crucial for regulating female body chemistry:

Spinal synthesis of estrogen is critical to the processes [of forming and using KOR/MOR heterodimers], and blockade of either estrogen receptor (ER) α-, β-, or G-protein-coupled ER1 or progesterone receptor (PR) substantially reduces KOR/MOR and eliminates mediation by KOR of spinal morphine antinociception.

In other words, a squirt of estrogen causes a sharp increase in the number of KOR and MOR receptors that get formed. This is a Big Deal, because some previous research suggests that in men, KORs and the chemicals that activate them may actually promote pain – and that their attachment to a MOR converts them to part of a pain-relieving system:

The research suggests that kappa-mu opioid receptor heterodimers could function as a molecular switch that shifts the action of kappa-opioid receptors and endogenous chemicals that act on them from pain-promoting to pain-alleviating.

To figure out what was going on with all these receptors, a team led by Alan Gintzler, a SUNY biochemist, first did some research to show that KOR and MOR opioid receptors join to form KOR/MOR heterodimers, the Journal of Neuroscience reports. This research was the first step toward understanding how these receptors interacted in the body’s pain system.

For this new study, though, the scientists injected estrogen and progesterone into the spinal cords of test animals, and determined that both chemicals were critical for the formation or KOR/MOR heterodimers, and these heterodimers’ activity in suppressing pain, as opposed to spreading it.

This discovery could go a long way toward explaining why certain pain-suppressant drugs that target MORs and KORs – such as pentazocine and nalbuphine – work well on women, but poorly on men: in spinal cords that lack the KOR/MOR heterodimer, the drugs might be activating the lonely little KORs, which – without their MOR friends, would help promote pain instead of relieving it. How rude of them.

Anyway, this new data looks like it’ll provide some encouraging ideas for future pain relief research:

The activation of the kappa-opioid receptor within the kappa-mu-opioid receptor complex could provide a mechanism for recruiting the pain-relieving functions of spinal kappa-opioid receptors without also activating their pain-promoting functions.

The researchers also point out that doctors should talk with women about where they are in their menstrual cycle before prescribing them medications like these – when estrogen and progesterone levels drop, pain relievers might turn into pain promoters.

So the moral of the story is, if you’re a guy (or a women who’s low on estrogen), some things really are gonna hurt me more than they hurt you.

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