Once you've touched a hot stove, you rarely make the same mistake. That painful lesson comes courtesy of protein molecules dotting the nerve endings in the skin that detect extreme heat and send the brain the message, "Yeowch!" Researchers thought they had identified the protein predominately responsible for detecting painful heat, but a new paper shows that neurons lacking that protein detect heat just fine, suggesting that a still-unmasked molecule might do most of the heat sensing.
Both extreme heat and capsaicin, the chemical that gives certain peppers and foods their fire, are thought to elicit pain by activating a cell surface protein, or receptor, called TRPV1 or VR1. Several years ago, for example, researchers showed that isolated nerve cells from mice genetically engineered to lack TRPV1 didn't react to painful heat or capsaicin (ScienceNOW, 13 April 2000). The story seemed to hold up in animals. When the tails of normal mice were immersed in exceedingly hot water, they quickly withdrew them, whereas mice without TRPV1 reacted in a more leisurely fashion. There were hints, however, that TRPV1 might not be the whole story: The engineered mice behaved just like the normal ones when their tails were dipped in hot, but not scalding, water.
While studying pain-responsive neurons, neurophysiologist Brian Davis of Pittsburgh University and his colleagues noticed that most heat-detecting neurons did not contain TRPV1, contrary to their expectation. The researchers then tested a preparation incorporating the skin, neuron, and spinal cord of a TRPV1-lacking mouse, which preserves the connections between different types of cells and mimics a living mouse better than a preparation of isolated neurons. In this "pseudointact" system, neurons from animals engineered to lack TRPV1 detect heat just fine, the scientists report in the 14 July Journal of Neuroscience. The data suggest that the receptor typically responsible for painful heat sensing remains to be identified, says Davis.
That may not rule out such a role for TRPV1, however. Multiple receptors probably participate in painful heat sensing under various circumstances, says study co-author Michael Caterina of Johns Hopkins University, who also authored the earlier paper. Different experimental methods may disproportionately detect one type over the other. "I don't think they're incompatible results," Caterina says.
Still, "many of us have come to assume that TRPV1 is synonymous with noxious heat detection," says cell physiologist Amy McDermott of Columbia University. This paper "forces the field to reconsider that assumption and to look for other detectors."