The biological pathway that determines how mice feel pain differs between males and females and could translate to humans leading to gender specific painkillers.
"This is the first ever demonstration of sex difference involving different cells," says lead author Jeff Mogil of Mcgill University.
Mogil and his team, whose research was published in Nature Neuroscience, looked at the biological pathway responsible for pain in both male and female mice, something that surprisingly had never been done before. The pathways, they found, were quite different.
In males, immune cells called 'microglia' are involved in the development of chronic pain. Among females, however, a different immune cell, the T-lymphocyte, is key to triggering the pain state.
In the experiments, mice with chronic pain caused by nerve damage were subjected to a stimulus that would normally be perceived as a light stroking sensation. These animals register the stimulus as painful, as do humans with similar injuries. People with this condition are said to be suffering from mechanical allodynia, and it's very common.
"Everyone has had mechanical allodynia," says Mogil. "If you've ever had a sunburn on your back and I came by and slapped you on the back, under normal circumstances that wouldn't be painful, but if you had a sunburnt back you would go through the roof!"
Before receiving a nerve injury, the mice in the study would tolerate up to 1 gram of force being applied to one of their hind paws before they hopped away. But, after injury, the animals withdrew from stimuli ten times smaller - just 0.1 or 0.2 grams of force, showing that they were experiencing allodynia.
Next, the animals were given drugs to block the function of the microglia cells thought to be the cause of the chronic pain.
"In males, the mice would go back to the withdrawal threshold of 1 gram, whereas in females they would remain down at 0.1 grams," says Mogil.
Speculating that another system or cell type must be involved to account for the difference between the two sexes, the team found that, in females, arresting the actions of T cells was required to achieve the same pain-relieving effect.
This suggests that, if the same is found to be true in humans, many drugs under current development could fail, as Mogil explains. "There is a great need for new painkillers and many of the compounds under development are actually working on this biological circuit that we have now shown only applies to males. The drug will fail in the clinical trials, which are, by law, half men and half women, and not help the half of the population that it could have helped."
Now that this gender difference has been identified it could lead to gender specific, or 'his n' hers' painkillers, according to Mogil.
"The idea of blue pills and pink pills for pain, I really believe that one of these years, that's actually going to be a reality!"
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