Scientists have found a reason why some people never seem to get warm while others never seem to feel the cold: some nerve cell receptors deep in the body are stimulated by signals other than temperature.

These cells never come in contact with environmental signals like those near the skin but are studded with receptors that appear to get sensory input from hormones, proteins and other biochemical compounds within the body.

The findings, published in 2004 in the Journal of Neuroscience by researchers at the University of Florida, advance the understanding of why menopause, depression and fevers sometimes cause chills along with feeling overheated.

'What we are working to understand is the physiological and pathological roles of these receptors and why some people may feel cold or pain despite external stimuli,' said neuroscientist Jianguo Gu, a researcher in the university's College of Dentistry and the McKnight Brain Center.

'That could explain why it is that you and I can sit in the same space and you will feel comfortable and I may feel cold, yet the environmental stimuli are the same.'

Other scientists have only recently identified hot and cold nerve cell receptors in the peripheral nervous system located just beneath the skin. This is the system that tells the brain to pull the hand back from the flame or to bundle up when it's cold outside.

But what Gu and his colleagues found is that there are receptors so deep in the body that they literally chill to the backbone. 'In addition to under the skin on the peripheral side of the nervous system, there are also cold receptors on the central side of the peripheral nervous system within the spinal cord,' he said.

The researchers studied the effects cool temperatures and menthol, a chemical derivative of peppermint associated with cooling effects, had on a specific sensory molecule found on the tips of peripheral nerves.

They placed central and peripheral nerve cells taken from rats together in lab dishes to mimic the cells' relationship to each other inside the body. Then they exposed the cells to cold and menthol.

'When they are together, just as in the body, these neurons make a connection called a synapse that transmits cold sensory information from the peripheral to the central nervous system neuron when stimulated by cold temperature and menthol,' Gu said.

'What makes this exciting is that the central terminal - or ending - of a peripheral nerve actually expresses the cold and menthol receptors.'

This response of the receptor is important because, inside an animal, those nerve cells are never exposed to environmental temperatures, and the researchers suggest that means they respond instead to biochemical substances inside the body.

'The finding that the cold receptor is present in a functional form at nerve terminals within the spinal cord is potentially quite exciting,' said Dr. Michael Caterina, a researcher at Johns Hopkins University School of Medicine who was the first to find hot receptors in the peripheral nervous system sensitive to heat and capsaicin, the chemical that makes hot peppers hot.

Doctors now use creams containing the substance to treat some arthritic conditions and neuralgic pain that comes from oversensitive nerve endings near the skin.

Caterina said it's unclear whether the cold receptors near the spinal cord are actually functional, or just an evolutionary leftover. But even if they serve no regular function, drugs that target the receptor might still be useful to alter spinal processing of sensory information in people suffering spinal injuries or other disorders, he suggested.

More research will be needed to understand how the mechanisms for activating the receptor work inside the body, Gu said. 'Right now, we really just don't know how this receptor might function in the central nervous system, but we see all these possibilities.'