UF Researchers Find Nerve Cell Receptors For Sensing Cold May Be More Than Skin Deep
GAINESVILLE, Fla. — Outside, the mercury may be rising, yet you can’t seem to warm up; in fact, you might feel downright chilled.
Now University of Florida scientists have found the first evidence to explain why, and it turns out it’s an inside job: Certain nerve cells in the body appear capable of transmitting the sensation of cold to the central nervous system without ever coming in contact with the outside environment like their brethren nearer the skin’s surface. Instead, these cells are studded with receptors that seem to receive sensory input from hormones, proteins or other biochemical compounds within the body.
The finding, published this month in the Journal of Neuroscience, is a step toward better understanding why menopause, depression or fevers sometimes cause chills.
“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 G. Gu, who is affiliated with the UF College of Dentistry and UF’s McKnight Brain Institute. “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.”
Skin is our largest and most versatile organ. Not only is it a 20-square-foot wash-and-wear raincoat for our internal organs, it also sends thousands of impulses to the central nervous system that enable the brain to interpret external conditions. Our skin allows us to find welcome relief in the chill of air-conditioning on hot summer days and compels us to bundle up when the air outside is nippy.
Other scientists have only recently identified the separate hot and cold nerve cell receptors in the peripheral nervous system, those nerves just under our skin that sense external environmental conditions and transmit that information to our central nervous system.
Picture the nerves of the peripheral nervous system laced under the surface of our skin like electrical leads on a circuit board, channeling external sensory information to the central nervous system at the spinal cord, deep in the body. The central nervous system receives this sensory information from the peripheral nerves and forwards it to the brain.
“We have, in this paper, found that, in addition to the cold receptors where you would expect to find them under the skin on the peripheral side of the nervous system, there also are cold receptors on the central side of the peripheral nervous system within the spinal cord,” Gu said.
Gu and his colleagues studied the effects cool temperature and menthol, a chemical property of peppermint associated with cooling effects, had on a specific sensory molecule found on the tips of peripheral nerves. To accomplish this, the research team placed central and peripheral nerve cells from rats together in laboratory 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 they do in the body, these neurons make a connection called a synapse that transmits cold sensory information from the peripheral neuron to the central nervous system neuron when stimulated by cold temperature and menthol,” Gu said. “We found the cold receptors on the central side of the peripheral neurons responded to the temperature stimuli. What makes this exciting is that the central terminal, or ending, of a peripheral nerve actually expresses the cold and menthol receptors.”
This central-side response of the cold receptor to environmental temperature is important because, inside the animal, those nerve cells are never exposed to environmental temperatures. That may mean they are present on the central side to receive stimuli from biochemical substances inside the body.
“The finding that the cold and menthol receptor is present in functional form at nerve terminals within the spinal cord is potentially quite exciting,” said Dr. Michael J. Caterina, a researcher from Johns Hopkins University School of Medicine who is credited with first identifying hot receptors in the peripheral nervous system sensitive to heat and capsaicin, the chemical in hot peppers that makes them hot.
Caterina added that it remains to be seen whether the cold receptor at the spinal cord level is actually functional or if it is just an evolutionary leftover. Even if the latter is true, drugs that target the cold and menthol receptor might still be useful for modifying the spinal processing of sensory information, Caterina said.
“Future studies will help us understand the mechanisms that serve as antagonists for this cold receptor,” 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.”