Researchers identify possible new targets for treating pain in women

August 18, 2011, SUNY Downstate Medical Center

Women and men experience pain, particularly chronic pain, very differently. The ability of some opioids to relieve pain also differs between women and men. While it has been recognized since the mid-nineties that some narcotic analgesics are more effective in women than men, the reason for this difference was largely unknown.

Narcotic analgesics decrease pain by activating opioid receptors, which are located on nerves that transmit painful sensations. Since levels of mu, delta, and kappa opiate receptors—the three main types of opioid receptor in the brain and spinal cord—are not thought to differ dramatically in men and women, it was difficult to understand why the effectiveness of some painkillers is dependent on sex.

Now, research supported by the National Institute of Drug Abuse (NIDA) has revealed that the same major types of opioid receptor interact differently, depending on sex. The spinal cord of female laboratory animals was found to contain almost five times more kappa-mu heterodimer—a complex of mu-opioid and kappa-opioid receptor—than the spinal cord of male animals. Furthermore, the amount of mu-kappa heterodimer in the spinal cord of the females was about four times higher when their levels of estrogen and progesterone were at their peak. Subsequently, researchers found that both estrogen and progesterone are critical for the formation of mu-kappa opioid receptor heterodimers.

This research was conducted by Alan Gintzler, PhD, professor of biochemistry, Department of Obstetrics and Gynecology, and his senior collaborators Sumita Chakrabarti, PhD, and Nai-Jiang Liu, PhD, at the State University of New York (SUNY) Downstate Medical Center

The discovery of a mu-kappa opioid receptor complex that is more prevalent in the of females than males and that is synchronized with the ebb and flow of ovarian hormones could explain why drugs used to treat pain, such as pentazocine, nalbuphine, and butorphanol—which primarily act on mu-opioid and kappa-opioid receptors—are more effective in women than men. 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 research by Drs. Gintzler, Liu, and Chakrabarti, which was recently published in the Proceedings of the National Academy of Sciences and the Journal of Neuroscience, 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. Kappa-mu heterodimers could serve as a novel molecular target for pain management in women.

Dr. Gintzler's research suggests that physicians should take the stage of the menstrual cycle into account before deciding which drugs to prescribe to treat pain in women. While some drugs might be very effective in treating pain at times when estrogen and progesterone levels are high, they could heighten pain when levels are low. "This consideration could become even more critical in managing in postmenopausal and elderly women," said Dr. Gintzler. "Further research is needed to flesh out these possibilities."

The Journal of Neuroscience paper appeared in the August 17, 2011 edition.

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not rated yet Aug 18, 2011
not rated yet Aug 19, 2011
This issue has been a nightmare for me personally. I'm one of the very unusual people (and a woman) who doesn't respond AT ALL to the typical pain relievers - morphine, fentenyl, oxycodine, oxycontin, percocet, etc. I get no side effects, no euphoria, just nothing - including zero pain relief, from them no matter the dose. It's not a built up tolerance either - it's been that way since day one. This is NOT pleasant when one has to have surgery, and I never could understand why things were so painful after compared to what seeemed to be expected. I assumed that's just the way it was for everyone. It's not. I only discovered this when I had a severe eye infection and a very bad reaction to the hydrocodone that was proscribed, so they switched me to demerol. I also get no side effects from it, and while it is a weak pain reliever relateive to the others, it is far far better than nothing. It's the only opioid that works on me. (continued next post)
not rated yet Aug 19, 2011
Doctors, however, in the last several years have decided that the other opioids are preferable, & for many 'demerol' is a dirty word. YOU try waking from major surgery and going several hours after with zero pain meds. It's like the f'ing dark ages. In the last few years I've had multiple spine surgeries, and this has been a big problem. Some docs know there are a few people like me - others don't. I've wound up turning down follow up scripts (why bother when they've zero effect?). I've even put down that I was allergic to the others but really don't like being forced to do that. It is insane in this day & age to have to go thru this sort of thing. I know of FOUR other women who are very similar & no men - so for a number of years now I have strongly suspected there was a serious gender difference that had to be tied into the kappa receptor (or a lack of mu receptor response). I hope to heck they'll get something figured out, because I for one am sick of being treated like this
not rated yet Aug 19, 2011
I'd probably be a great research subject for whatever doctors are studying this sort of thing. Wish to heck that weren't the case. I'd give just about anything to respond like the vast majority of people. And I'm still pre-menopausal... I KNOW I'll have to have more surgeries and dread the very idea anymore. If I ever get cancer, considering the pain problems so common as it advances... well, I'd be in an even far more horrible situation should that occur. I really do strongly suspect there are far more of us in this situation than the medical community & researchers even begins to realize. Up until the 90's IIRC virtually all of the research was conducted on men only, to avoid the hormonal fluctuations... After which the assumption was that pain meds worked pretty much the same on women - that one sure is turning out to be wrong! Far too many docs don't realize that even in men there can be a large difference in the dose necessary for effectiveness based on biochemistry alone.

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