Cold Comfort: Cool Receptors May Ease Chronic Pain

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Many injuries respond to cold. Sprains and inflammation can be eased by the timely application of some ice or a cold compress. And healers have known that cooling the skin can also block pain at least since the time of Hippocrates, the Greek father of Western medicine, who prescribed "a copious affusion of cold water" to reduce swelling and discomfort, "for a moderate degree of numbness removes pain." A few millennia later, modern researchers have identified the mechanism in the nervous system that gives rise to this effect and proved its efficacy for blocking pain in rats.

Recent research has shown that protein receptors on the outside of nerve cells variously signal hot or cold as well as other physical sensations such as taste and touch. One such receptor--TRPM8--is activated in a small number of nerve cells when the skin is cooled or cooling compounds, such as menthol or mint oil, are applied. Neuroscientist Susan Fleetwood-Walker and her colleagues at the University of Edinburgh chose to investigate this particular pathway as a potential pain reliever based on centuries worth of anecdotal evidence.

Rats with injured paws were either treated with topical solutions of icilin or menthol, or placed in a thin layer of water cooled to between 16 degrees and 20 degrees Celsius (61 to 68 degrees Fahrenheit) for five minutes. Both these treatments activated TRPM8, after which the rat¿s pain nerves fired less frequently. Also, blocking their TRPM8 receptors stopped the analgesic effect.


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The discovery of the cooling pathway--and its pain-blocking potential--opens up a new avenue of research for those suffering from chronic pain due to nerve injury, the researchers say in the paper presenting the finding in today's issue of Current Biology. "Our discovery means that patients can be given low doses of a powerful pain killer, delivered through the skin, without side effects," Fleetwood-Walker notes. Or they can try a little cold water, as Hippocrates advised.

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