For years scientists have debated the relative importance of brain function, genes, and hormones in causing contrasting pain sensations among men and women. "There is a definite need to better understand all the neurophysiological and psychosocial factors in how we experience pain," says Fillingim. Scientists believe the brain circuitry that regulates pain response and relief differs in women and women.

Women are Wired Differently
Women's hypersensitivity is partly because their brains are wired differently, says Jeffrey Mogil, an assistant professor of psychology at the University of Illinois at Urbana-Champaign.

In research on mice and rats, Mogil and his colleagues implicated a sex-specific gene. The unidentified gene(s) in this region accounts for up to 25% of the trait difference seen in female mice but not males. They also pinpointed a region of a mouse chromosome that contains a gene affecting pain sensitivity only in males.

"More and more it looks like there's actually different systems in men and women...that the physiology must differ by a protein being involved in a neural circuit in one case and not in the other," Mogil says.

Women are more sensitive to the same sensations and less tolerant than males in part because brain chemistry ebbs and flows with the menstrual cycle. New evidence suggests that certain women patients who experience more severe premenstrual pain symptoms may be hypersensitive in other ways.

Fillingim was amazed by how many patients he treated for TMJ had experienced early, painful periods. "They were out of whack from puberty," Fillingim says.

Hormones Linked to Painful Disorders
Hormones have been linked to other painful disorders such as rheumatoid arthritis, irritable bowel syndrome, and fibromyalgia. With such conditions as migraines and TMJ, the prognosis doesn't necessarily improve with age.

A study published in the April 2001 issue of Pain suggests that hormone replacement therapy can actually aggravate TMJ even in healthy menopausal women who are subjected to provocation. "The women on HRT reported being more pain-sensitive than those who were not," says Fillingim, who headed the study.