<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Gaudioso, Christelle</style></author><author><style face="normal" font="default" size="100%">Hao, Jizhe</style></author><author><style face="normal" font="default" size="100%">Martin-Eauclaire, Marie-France</style></author><author><style face="normal" font="default" size="100%">Gabriac, Mélanie</style></author><author><style face="normal" font="default" size="100%">Delmas, Patrick</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Menthol pain relief through cumulative inactivation of voltage-gated sodium channels.</style></title><secondary-title><style face="normal" font="default" size="100%">Pain</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Dec 13</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">ENG</style></language><abstract><style face="normal" font="default" size="100%">Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel. It is also frequently part of topical analgesic drugs available in a pharmacy, although its mechanism of action is still unknown. Compelling evidence indicates that voltage-gated Na(+) channels are critical for experiencing pain sensation. We tested the hypothesis that menthol may block voltage-gated Na(+) channels in dorsal root ganglion (DRG) neurons. By use of a patch clamp, we evaluated the effects of menthol application on tetrodotoxin (TTX)-resistant Nav1.8 and Nav1.9 channel subtypes in DRG neurons, and on TTX-sensitive Na(+) channels in immortalized DRG neuron-derived F11 cells. The results indicate that menthol inhibits Na(+) channels in a concentration-, voltage-, and frequency-dependent manner. Menthol promoted fast and slow inactivation states, causing use-dependent depression of Na(+) channel activity. In current clamp recordings, menthol inhibited firing at high-frequency stimulation with minimal effects on normal neuronal activity. We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na(+) channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na(+) channels, indicating a role for Na(+) channel blockade in the efficacy of menthol as topical analgesic compound.</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22172548?dopt=Abstract</style></custom1></record></records></xml>