<?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%">Duarte, Dejane Braz</style></author><author><style face="normal" font="default" size="100%">Duan, Jian-Hong</style></author><author><style face="normal" font="default" size="100%">Nicol, Grant D</style></author><author><style face="normal" font="default" size="100%">Vasko, Michael R</style></author><author><style face="normal" font="default" size="100%">Hingtgen, Cynthia M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Reduced expression of SynGAP, a neuronal GTPase activating protein, enhances capsaicin-induced peripheral sensitization.</style></title><secondary-title><style face="normal" font="default" size="100%">J Neurophysiol</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 Apr 27</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">ENG</style></language><abstract><style face="normal" font="default" size="100%">SynGAP is a neuronal specific Ras/Rap-GTPase activating protein (GAP) that increases the hydrolysis rate of guanosine triphosphate (GTP) to guanosine diphosphate (GDP), converting Ras/Rap from the active into the inactive form. The Ras protein family modulates a wide range of cellular pathways including those involved in sensitization of sensory neurons. Since GAPs regulate Ras activity, SynGAP might be an important regulator of peripheral sensitization and pain. Therefore, we evaluated excitability, stimulus-evoked release of the neuropeptide calcitonin gene-related peptide (CGRP), and nociception from wild type mice (WT) and those with a heterozygous mutation of the SynGAP gene (SynGAP(+/-)). Our results demonstrate that SynGAP is expressed in primary afferent sensory neurons and that the capsaicin-stimulated CGRP release from spinal cord slices was two-fold higher from SynGAP(+/-) mice than that observed from WT mouse tissue; consistent with an increase in expression of the capsaicin receptor, TRPV1, in SynGAP(+/-) dorsal root ganglia. However, there was no difference between the two genotypes in potassium-stimulated release of CGRP, the number of action potentials generated by a ramp of depolarizing current, or in mechanical hypernociception elicited by intraplantar injection of capsaicin. In contrast, capsaicin-induced thermal hypernociception occurred at lower doses of capsaicin and had a longer duration in SynGAP(+/-) mice than WT mice. These results provide the first evidence that SynGAP is an important regulator of neuropeptide release from primary sensory neurons and can modulate capsaicin-induced hypernociception; demonstrating the importance of GAP regulation in signaling pathways that play a role in peripheral sensitization.</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21525372?dopt=Abstract</style></custom1></record></records></xml>