http://www.eurekalert.org/pub_releases/2009-02/plos-cph021909.php Public release date: 23-Feb-2009
Contact: Sally Hubbard
press@plos.org
Public Library of Science
Chili peppers help to unravel the mechanism of pain
Press release from PLoS Biology
Capsaicin, the active ingredient in chili peppers, is most often experienced as an irritant, but it may also be used to reduce pain. A new work published by Drs. Feng Qin and Jing Yao in this week's PLoS Biology uses capsaicin to uncover novel insight into how pain-receptor systems can adapt to painful stimuli. Sensory systems are well known to adapt to prevailing stimuli. For example, adaptation happens when your eyes adjust from a dark movie theater during a matinee to the bright sunlight outside. Whether pain receptors truly adapt or rescale their responses (versus simply desensitizing) has been an open question.
Capsaicin acts by binding to a receptor in the cell wall of nerve endings and triggering an influx of calcium ions into the neuron. Eventually, the nervous system interprets this cascade of events as pain or heat, depending on which nerves are stimulated. Scientists had previously linked the pain-relieving effects of capsaicin to a lipid called PIP2, found in cell membranes. When capsaicin is applied to the skin it induces a strong depletion of PIP2 in the cell membrane.
"The receptor acts like a gate to the neurons," said Qin. "When stimulated it opens, letting outside calcium enter the cells until the receptor shuts down, a process called desensitization. The analgesic action of capsaicin is believed to involve this desensitization process. However, how the entry of calcium leads to the loss of sensitivity of the neurons was not clear."
Capsaicin creams are commonly sold over the counter as effective treatment for a variety of pain syndromes, from minor muscle or joint aches to those that are very difficult to treat, such as arthritis and neuropathic pain.
… http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000046 Interaction with Phosphoinositides Confers Adaptation onto the TRPV1 Pain Receptor
Jing Yao, Feng Qin*
Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America
Adaptation is a common feature of many sensory systems. But its occurrence to pain sensation has remained elusive. Here we address the problem at the receptor level and show that the capsaicin ion channel TRPV1, which mediates nociception at the peripheral nerve terminals, possesses properties essential to the adaptation of sensory responses. Ca2+ influx following the channel opening caused a profound shift (∼14-fold) of the agonist sensitivity, but did not alter the maximum attainable current. The shift was adequate to render the channel irresponsive to normally saturating concentrations, leaving the notion that the channel became no longer functional after desensitization. By simultaneous patch-clamp recording and total internal reflection fluorescence (TIRF) imaging, it was shown that the depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) induced by Ca2+ influx had a rapid time course synchronous to the desensitization of the current. The extent of the depletion was comparable to that by rapamycin-induced activation of a PIP2 5-phosphatase, which also caused a significant reduction of the agonist sensitivity without affecting the maximum response. These results support a prominent contribution of PIP2 depletion to the desensitization of TRPV1 and suggest the adaptation as a possible physiological function for the Ca2+ influx through the channel.
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