Research suggests that men and women use separate mechanisms in the brain to achieve pain relief.

More than 50 million Americans live with chronic pain, while millions more suffer bouts with acute pain due to injuries or surgery.

And while both men and women endure this affliction, pain is not always an equal opportunity burden: women are more apt than men to suffer from chronic pain and experience more severe and longer lasting pain.

Moreover, research shows that men and women also respond differently to pain medications and an increasing number of studies suggest that the fundamental biology of pain and pain relief differs between the sexes.

In fact, accumulating evidence implies that the days of sex-specific pain killers — perhaps pink and blue pills — may not be too far off.

The first hint that pain medication might work differently in men and women came as a surprise to researchers at the University of California at San Francisco (UCSF). They gave morphine-like painkillers called "kappa opioids" to patients who had undergone surgery to remove their wisdom teeth.

The drugs gave more powerful and long-lasting pain relief to women compared with men. In addition, at some doses, kappa-opioids were exceptionally good pain relievers in women and actually made the pain worse for men. Understanding the cause of this discrepancy will lead to better pain relief for both sexes.

Sex-specific pain relief is not just a phenomenon confined to opioids. Recent research shows that ibuprofen, the active ingredient in a number of over-the-counter medicines, may be much less effective in women than men.

Researchers at the University of New South Wales in Australia randomly gave a small group of men and women either ibuprofen or a sugar pill and then used electricity to cause experimental pain. They discovered that ibuprofen gave significant pain relief only in men.

New Research Implicates Genetics

New research by Jeffrey S. Mogil, professor of psychology at McGill University in Montreal, Canada, suggests that men and women use separate mechanisms in the brain to achieve pain relief.

By studying genetically modified mice, Mogil and colleagues have discovered that kappa-opioids, the same pain relievers UCSF researchers found were more effective in women, work through different pathways in female and male mice.

These scientists have identified the exact gene that controls for this sex difference in mice and are currently working on identifying the human gene equivalent.

Mogil's research suggests that men and women are wired differently for pain relief. Finding the genetic cause for this difference may lead to the development of a completely new class of pain relievers.

These hypothetical drugs would be the first example of a medication unrelated to reproduction that works in exclusively in one sex.

Why Do Pain Medications Work Differently in Men and Women?

While Mogil's research implicates differences in brain biochemistry, the question of why pain killers work differently in men and women is far from answered. Hormones, anatomy and sociocultural factors may also play a role.

Research suggests that a woman's sensitivity to pain changes throughout the menstrual cycle due to fluctuating levels of the hormones estrogen and progesterone. Other studies indicate that women's freedom with expressing pain may boost the perceived effectiveness of pain relievers.

What's more, women are more apt to be dependent on so-called "polytherapy" to alleviate pain. For example, women often combine prescription medications with relaxation techniques such as yoga and psychotherapy to help them manage pain.

Thus, biological differences may interact with social and cultural issues to produce the observed sex differences in pain relief. Only further research examining the underlying cause of these sex differences will sort out the relative impact of each one of these factors.

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