Are there differences between the male and female brains? That's a rather loaded question, and one that has generally been asked in terms of behaviors and aptitudes—for example, there has been an extended debate about a math gap between the sexes that now appears to be a product of culture. But there does appear to be a distinct difference between the nervous systems of men and women. It just appears at a far more basic level: pain.

In the jargon-rich opening sentence of a paper that's being released by PNAS, "Sexually dimorphic nociception and opioid anti-nociception is very pervasive but poorly understood." Once you know that nociception is the sensing of noxious things like pain and that opioids are, well, opiates, however, it becomes much easier to follow: men and women differ in their sensing of pain and responses to drugs that block it. There are a significant number of papers that detail finding these differences in humans and other mammals, as well as the general finding that women are more likely to suffer from chronic pain ailments.

The one thing we haven't figured out yet is why, although the new paper goes some way in that direction. It looks into the expression of the proteins that act as receptors for opioids, both the ones that our own bodies produce and the synthetic ones we use as pain killers. There are several classes of these opioid receptors, but the researchers focus their attention on the mu and kappa (μ and κ) forms.

The genes for these receptors encode proteins of a very specific size and, if you look in the spinal cord of male rats, you'll find a protein with the predicted size. If you look in the spinal cord of female rats, however, you'll find that most of the proteins appear to be twice that size. What's going on? The authors take pains to show that this larger complex is a result of one copy each of the μ and κ receptors associating with each other, forming what's called a heterodimer.

In fact, there's about four times as much of this heterodimer around in females than they could detect in males. In addition, the levels of the complex change as the females go through their estrous cycle. The complex also appears to be essential for pain relief. Males can feel the effects of morphine if they only have active μ receptors around. Females, however, appear to require both μ and κ receptors to be active in order to experience the pain relief of morphine.

Overall, the paper isn't fantastic. There are some additional experiments and better controls that might have made for a more convincing case. The authors also spend part of their discussion engaged in some heavy speculation, pondering why men and women might end up with different pain management systems.

But the experiments that are there seem very solid, and not all the discussion is quite so speculative. The authors note that the changes in this complex appear to be under hormonal control, given that it changes with the estrous cycle. The intriguing question is how hormones can regulate this association. Given the relative size of the heterodimer and individual proteins, it doesn't appear that there's another molecule that holds the complex together in females, so the question of why they have a distinct response to pain is only partially solved by these findings.

PNAS, 2010. DOI: 10.1073/pnas.1009923107 (About DOIs).