TRPM8 is responsible for detecting the sensation of both cold temperatures and menthol.

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CANBERRA: The sensation of cold and the cool feel of menthol are detected by the same protein, and the find may lead to new painkillers, say scientists.

"It's been known for years that menthol and related cooling agents evoke the 'psychophysical' sensation of cold – somehow by interacting with the aspect of the sensory nervous system that's related to cold detection," said physiologist David Julius, from the University of California in San Francisco, USA.

But scientists have been unsure exactly how the nervous system detected the sensation.

In 2002, Julius and his team first proposed that a single receptor – called the menthol receptor or TRPM8 – may be responsible for the sensation from both chemical cooling agents, such as the menthol, and cold temperatures. As they detail today in the British journal Nature today, experiments in mice have now allowed them to prove it.

Cool gateway

They found that TRPM8 sits in the cell membrane of neurons in the skin. It forms a gateway that opens when the body is exposed to cold temperatures or menthol, allowing calcium ions to flood into the cell. Cold temperatures are detected by the peripheral nervous system, and sent via the central nervous system to the brain. The brain interprets those signals as a cool feeling.

For the study, Julius and his team bred transgenic mice without the gene coding for the TRMP8 receptor. When neurons from normal mice are cultured in a lab, the receptor opens as temperatures drop down to about 26°C. However, the researchers found that in the lab neurons from the mutant mice barely responded to the falling temperatures.

The team went on to observe the behaviour of normal and mutant mice when exposed to cool temperatures. The 'flinching' response to cold seen in normal mice, were substantially reduced in mutant mice exposed to a cold surface.

The mice were put in a chamber with two adjacent surfaces – one held at 30°C, while the other ranged from 49°C to 5°C. The mutant mice showed very little preference for the plate at 30°C, until temperatures dropped below 15°C. Even when the temperature was that low, the mice would still spend extended periods exploring the cold plate – a behaviour not observed in normal mice.

Pain pathway

The researchers argue that this suggests TRPM8 is responsible for detecting cool temperatures, while another receptor may be kick in to detect dangerously cold temperatures.

Humans also have the TRMP8 receptor, and it's though to work in the same way. The findings may eventually lead to a new breed of painkillers, said Julius, as they also appear to be involved in a pathway for sensing pain.

"By understanding how sensory receptors work, [and] 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," he said.