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Detecting cold, feeling pain: Study reveals why menthol feels fresh

Scientists have identified the receptor in cells of the peripheral nervous system that is most responsible for the body's ability to sense cold.

The finding, reported on-line in the journal "Nature" (May 30, 2007), reveals one of the key mechanisms by which the body detects temperature sensation. But in so doing it also illuminates a mechanism that mediates how the body experiences intense stimuli – temperature, in this case – that can cause pain.

As such, the receptor – known as menthol receptor TRPM8 -- provides a target for studying acute and chronic pain, as can result from inflammatory or nerve injury, the researchers say, and a potential new target for treating pain.

"By understanding how sensory receptors work, how thresholds for temperature are determined, we gain insight into how these thresholds change in the setting of injury, such as inflammatory and nerve injury, and how these changes may contribute to chronic pain," says senior author David Julius, PhD, chairman and professor of physiology at UCSF.

The methanol receptor, and other temperature receptors discovered in recent years by the Julius lab, offer potential targets for developing analgesic drugs that act in the peripheral, nervous system, rather than centrally, where opiate receptors act, he says.

The finding is a milestone in an investigation the team began several years ago. In 2002, the researchers discovered that the receptor was activated by chemical cooling agents such as menthol, a natural product of mint, and cool air. They reported their discovery, or "cloning," of the receptor in "Nature" (March 7, 2002), hypothesizing that the receptor would play a key role in sensing cold. However, some subsequent papers questioned this theory.

In the current study, the team confirmed their hypothesis by "knocking out" the gene that synthesizes the receptor, both in sensory neurons in cell culture and in mice. The cells in culture were unre
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Source:University of California - San Francisco


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