Researchers find more evidence of estrogen's role in female pain
February 25, 2013
By C.J. Janovy
Scientists at the University of Kansas Medical Center continue to further our understanding of how estrogen — the hormone that most defines femininity — paradoxically contributes to female pain syndromes.
Researchers in the Women's Pain Division of KU's Institute for Neurological Discoveries have done pioneering work on how estrogen contributes to migraines. Now a group of researchers has published a paper in January's Journal of Neuroscience that establishes a link between estrogen and pelvic pain.
"We've known for some time that estrogen can modulate pain," says Peter Smith, Ph.D., professor in the Department of Molecular and Integrative Physiology and director of KU Medical Center's Institute for Neurological Discoveries. "Some types of pain are associated with a drop in estrogen, as occurs on menopause, or an inability to respond to estrogen, which can happen to women in their teens and twenties."
Smith says the study explores a new function for a protein called BMP4 is shedding new light on exactly how that happens.
"This particular molecule appears to be important in making sure you have the right number of pain-sensing nerves," Smith says. Working with rodents, the researchers were able to show that when estrogen levels rise, BMP4 levels go down, resulting in fewer pain-sensing nerves. The fact that estrogen suppresses the ability to produce BMP4 wasn't appreciated before, Smith says.
"We now have a mechanism that explains how, under normal conditions, peripheral sensory nerves - the pain-sensing terminals - go into a phase of rapid growth in female pelvic pain syndromes," says Aritra Bhattacherjee, a doctoral student in Smith's lab who is the paper's lead author. "Sensory nerve growth can have significant implications in different pain syndromes — knee pain, joint pain, other inflammatory conditions, tendonitis, vulvar pain," Bhattacherjee says. "Such inflammatory pain syndromes are highly prevalent with no effective cure."
"We're realizing now that there are a number of female pain syndromes out there, and certain types are quite prevalent," Smith says. "One of those is pelvic pain, so understanding what determines these pelvic pain syndromes is important."
A decade ago, in a study of nearly 5,000 ethnically diverse women in Boston, Harvard researchers determined that 16 percent had histories of "chronic burning, knife-like pain, or pain on contact" that lasted at least three months. "Nearly 40 percent of women chose not to seek treatment, and of those who did, 60 percent saw three or more doctors, many of whom could not provide a diagnosis," the researchers wrote. Their conclusion: "Chronic unexplained vulvar pain is a highly prevalent disorder that is often misdiagnosed."
For women, estrogen levels rise and fall during the reproductive cycle, resulting in rising and falling numbers of nerves in the pelvic region — perhaps out of necessity. "When a pregnant woman is close to term," Bhattacherjee points out, "estrogen levels shoot up, lowering the numbers of pain-sensing terminals in the reproductive tract, which may help in the delivery."
What's particularly exciting about this study, Bhattacherjee says, is that most studies of BMP4 in the adult nervous system come from injury-related models. But for the first time, KU Medical Center researchers studied a model that did not involve an induced injury. "Nerve injury may lead to activation of BMP-signaling," he says. "What's novel is that we, for the first time, show a role for BMP4 in causing nerves to grow under normal conditions not induced by injury."
Bhattacherjee, a Ph.D. student who is scheduled to defend his dissertation later this month, says he's excited about the results of the research.
"It's important to be able to contribute to this area," he says. "In the bigger picture, this is really a gateway for us to understand nerve regeneration and nerve growth. It has broader implications for spinal cord injury, intellectual and developmental disabilities, and other developmental neurological disorders, because the BMP4 signaling pathway is involved in many other nervous system functions."
Hinrich Staecker, M.D., Ph.D., a professor in the KU Medical Center's Department of Otolaryngology, and M. A. Karim Rumi, M.B.B.S., Ph.D., a research assistant professor in the Department of Pathology and Laboratory Medicine, also contributed to the study.
This study was supported by the Eunice Kennedy Shriver National Institute Child Health and Human Development of the National Institutes of Health under award numbers HD049615 and HD002528.