Lakhasly

Levine was just testing painkillers on people who'd had a wisdom tooth extract- ed, when he uncovered rather more than he'd bargained for.The women in his study group found that strong painkillers related to morphine, called kappa-opioids, were most effective at numbing pain.'In fact, the doses used in the clinical trial made pain worse for men,' says Levine, a clinical neuroscientist from the University of California in San Francisco.But the same drugs didn't work for the men at all.

Levine was just testing painkillers on people who'd had a wisdom tooth extract- ed, when he uncovered rather more than he'd bargained for. The women in his study group found that strong painkillers related to morphine, called kappa-opioids, were most effective at numbing pain. But the same drugs didn't work for the men at all.

'In fact, the doses used in the clinical trial made pain worse for men,' says Levine, a clinical neuroscientist from the University of California in San Francisco.

He was shocked, "The idea that a therapy that had been around for decades could affect men! and women in such dramatically different ways was anathema,' he says. 'It was such an incredible mindset in the field of pain, missing what had clearly gone on in front of their eyes for years!It is not an effect specific to opioids, either. Another recent study showed that ibuprofen, a widely used anti-inflammatory drug, can be much less effective for women than for men. Researchers at the University of New South Wales found that when they used mild electric shocks to induce pain in healthy young people, only the men got any relief with ibuprofen. It was only a small study, but still worrying, as the drug is often marketed with women in mind.

It's been five years now since Levine first spotted a sex difference, yet we still don't know why it exists. And when it comes to testing or prescribing painkillers, or studying pain, noth-. ing much has changed. Remarkably, even many of those involved in pain research are unaware of these findings. 'I myself have never been able to get relief from ibuprofen and now I under- stand why', says Marietta Anthony, a pharmacologist at Georgetown general clinical research center It's perhaps no surprise that the differences have eluded scientists for so long. Pain is mul- tidimensional and highly subjective, and there- fore very difficult to study. It varies with the time of day, age, diet, stress, genetic back- ground and so on... 2

But not only that. Only 10 years ago, phar- maceutical products were tested almost exclu sively on men. Women were left out of the tests in case their inconveniently fluctuating hor- mones messed up the analysis. Only in 1993 did the US make it a legal requirement for women to be included in clinical trials. According to a recent report, on average, 52 per cent of the subjects in large-scale trials are women. This looks like progress - but it's not. The figure includes women-only studies such as those investigating hormone therapies or drugs to treat breast cancer. And when testing. medications for diseases common to both sex- es, women's and men's results are often still lumped together, burying any differences in a statistical quagmire.

To Marietta Anthony, who was previously acting deputy director of the Office of Women's Heath at the FDA (Food and Drug Adminis- tration), change is imperative. If a drug works differently in men and women this information should be clearly displayed on the label. 'Side effects and efficacy really are different in men and women,' says Anthony. [and] there may be a very fundamental biological reason.'One of the more obvious biological reasons is that men and women tend to suffer from dif- ferent disorders, mostly the result of a complex bag of hormones, reproductive status and anatomy. So differences in how women and men report feeling pain have often been dis- missed as being solely down to the pain's dif- ferent origins. But origins aside, there's grow- ing evidence that even when the source is the same, the biochemical signals, nerve connec- tions and the way the brain handles pain are all quite different in the two sexes.

According to Knox Todd, a specialist in the assessment and treatment of pain at Emory University in Atlanta, Georgia, the differences even make their way into the clinic. 'What we see in the emergency department is that males make a public display of stoicism, ask for no pain medication, and keep up a good public front. But their stoicism evaporates as soon as men leave the hospital to go home, he says.

But who wins in the end? Is having a higher pain threshold good or bad? To women, pain is a wake-up call to sort out the problem before it gets too big. Men, who can put up with more, postpone asking for help until it's too late.. Women's prompt action could be at least part of the key to their longer life expectancy.