Hot Peppers and Pain

it was not until 1997 that a capsaicin receptor was 1056. terina et al., 1997), which they named the vallinoid recep-3505–3517. heat was activating the VR1 directly or through other thermally sensitive molecules. This study also generated a host of other questions regarding the endogenous ligand for the VR1: its physiological function, which neu-rons express the VR1 protein, and whether there are other VRs in sensory neurons or other areas of the brain. In a recent paper (Tominaga et al., 1998) in the Sep-tember issue of Neuron, the combined efforts of the Julius and Basbaum labs elegantly address several of these important questions. Using excised membrane patches, they show that heat gates VR1 directly and Capsaicin, the main pungent ingredient in hot chili pep-that an increase in protons, at levels that occur at sites pers, has been used for centuries as a spice. Aside of inflammation, infection, or ischemia, activates VR1 at for its expanding culinary use, in the past 2 decades room temperature. In light of this data, they propose a capsaicin has also provided remarkable insight not only model that highlights the notion that vallinoids, heat, into the neurobiology of primary afferent nociceptors and protons act in concert to regulate VR1 activity and but also into new treatments for chronic pain. that the effects of any one stimulus cannot be consid-The major reason that capsaicin has been so useful ered in isolation. Thus, whether thermal or chemical is its remarkable cellular specificity. Nearly all of the stimuli will be important in activating VR1 in vivo will actions of capsaicin can be attributed to a single mecha-likely vary with the site and degree of the injury. As an nism—activation of a nonspecific cation channel in a example, they suggest that whereas both temperature population of primary afferent sensory neurons known and pH would be expected to play a role in VR1 activa-as C fibers, 80% of which are polymodal nociceptors. tion in skin, in areas such as the viscera where tempera-Polymodal nociceptors are activated by noxious ther-ture is more constant, pH and not temperature will play mal, mechanical, or chemical stimuli and as such are a more important role in VR1 activation. The authors thought to be intimately involved in the generation and then go on to suggest that VR1 functions as an integrator maintenance of chronic pain. The belief among many of multiple pain-producing stimuli. What is particularly …