Recently, scientists understood little of how peripheral neurons detect thermal and pain stimuli. In 1997, a scientist reported the discovery of the cellular receptor for capsaicin. The capsaicin receptor is a protein channel that sits in the outer membrane of specific nerve cells and allows a flood of calcium ions to enter the cells when capsaicin is present. It is also the first mammalian member of a similar proteins called transient receptor potential or TRP channels. Consequently, they have discovered five other thermosensitive TRP channels, each tuned to a specific range of temperatures. The founding member of the family became known as TRPV1 because it recognized a vanilloid molecule. It is the best-studied of the thermoTRPs. Unlike V1, V2 does not respond to capsaicin but it does to heat with threshold higher than that of V1 in cultured cells. Meanwhile, the warmth-sensing neurons fire at V3 and V4 thresholds because they contain warmth-sensitive V3 and V4 channels. In 2003, a new channel called cold and menthol receptor 1 also known as TRPM8 was discovered. The channel seems to adapt to prolonged cold stimuli, and its threshold shifts to a warmer range when menthol is present, suggesting that the stimuli act synergistically. Overall, the biophysical properties of each heat-sensing channel are unique, with different thresholds and chemical sensitivities. Mysteries of pain, linked in temperature and touch sensation are flickering into view, erasing the uncertainties in the field at a remarkable rate.
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