11 March 2004

The sex hormones, gender and pain

More interesting stuff. (the mu-opioid system is the main anti-nociceptive system for modulating pain. Its the system that opiate drugs (morphine, heroin, etc) affect.

In July, 2001, the U-M team published a paper in the journal Science that contained the first glimpse of the brain's mu-opioid system in action, and confirmed the system's important role. Using a radioactive tracer attached to a molecule that only binds to mu-opioid receptors, they showed on PET scans that the endorphin systems became activated in the brains of 20 volunteers who were subjected to moderate levels of pain in their jaw muscle over 20 minutes.

That activation of endorphin release also corresponded with a drop in the volunteers' perceived pain and pain-related emotions - thereby linking the physical response with the emotional one.

Armed with the ability to see the brain's response to pain, Zubieta's team began looking at how that system handled pain in people of different genders, hormone levels and genetic makeup.

Study participants were scanned as they received a pain-causing but harmless injection of salt water in their jaw muscle.
They used the same double-blind, placebo-controlled jaw pain model, induced by a harmless injection of salt water into the masseter muscle, for all the studies. The injection is meant to simulate a condition called temporomandibular joint pain disorder, but is also a useful human model of sustained pain, and physical and psychological stress. Subjects rate their pain often during the PET scan, and the injection is controlled to keep the pain level the same at all times, so that unnecessary suffering is avoided. Subjects fill out standardized questionnaires after the scan, about how the pain made them feel.

In June 2002, the team reported in the Journal of Neuroscience the first findings that some of the differences between individuals in response to pain are governed by the mu-opioid system. In the study, 14 men scanned before and during jaw pain showed increases in endorphin release in certain brain areas during the painful state, as shown in the previous study. But most of the 14 women studied actually showed a reduction in endorphin release. The women also reported feeling more intense pain, and more pain-related negative emotions, than the men.

Zubieta notes that all the women were studied at a time in their menstrual cycle when levels of estrogen and progesterone were lowest.


For their latest pilot study, the team scanned healthy women once during their early follicular phase, and again during that same phase in another month - after they had been wearing an estrogen-releasing skin patch for a week. The patch made their levels of estrogen rise to levels normally seen during later parts of the menstrual cycle. This allowed the team to study estrogen's effect without the effects of other hormones, such as progesterone, that normally increase along with it.

...Scans made without the painful jaw stimulus showed that under high estrogen conditions, the number of available mu-opioid receptors, where endorphins would dock in case of pain, increased in several pain- and stress-controlling areas of the brain.

When the painful jaw injection was given, the effect of the estrogen on the capacity to activate this painkiller system was also striking. Instead of the low or absent activation of the mu-opioid system seen in women during low-estrogen conditions, the same women under high-estrogen conditions showed a marked increases in their ability to release endorphins and activate the receptors.

In other words, they had a response to pain that was more like the men in the previous study. And the effect was seen in multiple brain areas involved with the perception and regulation of pain, and of other stressful and emotionally significant stimuli

This isn't in the story, but its worth mentioning: there are actually thought to be three independent systems for pain modulation. I couldn't even begin to explain how the second one works, but the third is thought to only exist in women and, from what I've read, it is thought to be regulated by estrogen. Thus I'm not sure how the results of this study bear on the alleged third system. It might be that these results show the third system to be part of the main mu-opioid system, or that men and women lack a common mu-opioid system.
Categories: ,