Cooling Analgesia Offers Chronic Pain Relief

A novel biologic mechanism has great potential for relieving the suffering of millions of chronic pain patients by applying cooling analgesia, according to a new study.

Researchers from the University of Edinburgh (Scotland, UK) found that certain cooling chemicals, either injected or simply applied in small doses to the skin, have a dramatic natural painkilling effect on chronic pain in rats. They first induced chronic pain in the animals by tying a thread around a thigh, and then either injected a very small dose of icilin into the spinal cord or had the rats stand in a shallow bath of the chemical. They then stroked the painful limb and checked the rats' response. Those treated with icilin could withstand three times as much pressure.

The analgesic effect occurs through activation of a recently identified protein called TRPM8 that is expressed in nerve cells in the skin and responds to both cool temperatures and cooling chemicals. Activating the cold-sensing receptors sends a signal to the nerve's terminus in the spinal cord, where it then prevents other nerves from transmitting information about pain. The study appeared in the August 2006 issue of the journal Current Biology.

"The terminals are actually touching pain-transmitting nerves and stopping them from being activated,” said lead author Prof. Susan Fleetwood-Walker, of the Center for Neuroscience Research at the University of Edinburgh. "If you just looked at the nerve itself you wouldn't know that it's having this gating control over all the other nerves. It's only by looking at the whole animal that you can see this.”

Approaches using cooling compounds that activate the TRPM8 protein could be used for chronic pain patients, making use of the body's own capacity to suppress pain. The discovery of a novel biologic mechanism by which cooling analgesia works therefore has great potential for relieving the suffering of millions of chronic pain patients.

TRPM8 belongs to an interesting class of proteins whose members mediate the sensation of diverse stimuli, including taste, temperature, and touch. In addition to icilin and cold, TRPM8 is also activated by menthol and eucalyptol.



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