It's one of the more puzzling observations in medicine: the vast majority of chronic pain patients are women. Women suffer disproportionately from irritable bowel syndrome, fibromyalgia, headaches (especially migraines), pain caused by damage to the nervous system, osteoarthritis, jaw problems such as temporomandibular joint disorder (TMD) and much more. Women also report more acute pain than men after the same common surgeries.
In the lab, when researchers ask male and female volunteers to subject themselves to experimental pain - increasingly hot stimulation on the inner arm, immersion of the hand in very cold water, electrical jolts to the skin - women show lower pain thresholds (that is, they report pain at lower levels of stimulus intensity) and lower tolerance (they can't bear intense pain as long).
Women are also better able to detect small gradations in pain stimuli and respond differently to certain opioid - painkilling - drugs. (It's not clear if men and women differ in sensitivity to cancer pain.)
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But it's only recently that researchers have begun to study the exact genetic, physiological, hormonal and psycho-social factors that may underlie these sex differences. In part, that's because pain researchers have been hampered by one rather shocking fact: most basic pain research is still done in male mice and rats.
''This has been a catastrophe,'' McGill University pain geneticist Jeffrey Mogil says. He says the old rationale that menstrual cycles make females too difficult to study is bogus. Men and women, in fact, can be so different in the way their nervous systems process pain that one day there may be ''pink pills for women and blue pills for men,'' he says. The lopsided research exists solely because of ''inertia'', he adds.
Others agree, among them Dr Roger Fillingim, lead author of a 2009 review of sex and pain research published by the American Pain Society. In that paper, Fillingim, a pain researcher at the University of Florida, says that while the United States National Institutes of Health now require inclusion of both sexes in human studies, much animal research ''continues to eschew females''. As pain is mainly a female problem this means research ''that excludes females is incomplete at best and invalid at worst''.
Luckily, this shut-out is not total, some human research does specifically address sex differences, with complex and fascinating results. Take hormones. Growing up, boys and girls show comparable patterns of pain until puberty, says Dr Navil Sethna, a pediatric anaesthesiologist at the Children's Hospital Boston.
''After puberty, certain types of pain are more common in girls and, even if the incidence is the same, reported pain severity is more intense in girls than boys, especially for headaches and abdominal pain,'' says Sethna. This pattern persists through adulthood; the lifetime prevalence for migraines is 18 per cent for women and 6 per cent for men.
The same pattern holds for TMD, with no gender differences noted before puberty and significant differences afterwards.
Not all studies agree but many do show that, after puberty, women experience striking fluctuations in their response to pain at different points in the menstrual cycle. This has been noted in irritable bowel syndrome, TMD, headache and fibromyalgia. One explanation, some researchers say, is that oestrogen protects against pain at high levels and enhances it at low levels. (The male hormone testosterone seems to protect against pain.)
This theory fits with the observation that during pregnancy, when oestrogen levels are high, women often get fewer migraines and TMD pain. And it fits with the observation that, after childbirth, when oestrogen falls abruptly, the number of migraine attacks increases.
It may not be the absolute level of oestrogen that is key, says Dr Fernando Cervero, a pain researcher at McGill, but the fluctuations in hormonal levels during the menstrual cycle. (Oestrogen levels climb in the first half of the cycle, then decline in the second half.) ''It's the change that produces the change'' in perceptions of pain, he says.
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