Why do women and men feel pain differently? How do naturally fluctuating estrogen levels affect the experience of pain? How do they affect memory?
Jon-Kar Zubieta of the University of Michigan has used positron emission tomography (PET) imaging to investigate how men and women differ in the activation of an innate pain-relief circuit, the mu-opioid neurotransmitter system. His group has previously shown that during periods of low estrogen (such as shortly after menstruation), women were less able to activate this endogenous “anti-pain” system, and reported higher pain levels than men. Zubieta has now found that when estrogen levels are high (accomplished with an estrogen patch), women’s opioid system responses were equal to or exceeded those of men.
“Estrogen modulates the brain’s pain-suppression system, allowing it to become more active when necessary,” Zubieta says, which suggests that pain is “a more complex phenomenon in women.” Females may require this “flexibility” in pain control for situations such as pregnancy, recent birth, or menstrual fluctuations. For example, at the end of human pregnancy, estrogen levels may be 100 times normal; these levels may “tune up” the pain relief circuit to better counteract pain.
At the same time, there are suggestions from animal studies that high estrogen levels may also “tune down” certain kinds of memory. An overactive opioid system, for example, can decrease the ability to retrieve information from memory (“recall memory”). Studies in deer mice by Liisa Galea of the University of British Columbia have found that high estrogen levels impair working memory, while low estrogen levels facilitate it.
Whether this is nature’s way of ensuring that females don’t swear off childbirth, by revving up the brain to both suppress pain and “forget” it, is an open question. More practically, this research may lead to an understanding of why women are at greater risk for certain pain syndromes and how pain medications might need adjustment based on women’s menstrual cycles.