Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Although odontogenic infections are often accompanied by pain, little is known about the potential mechanisms mediating this effect. In this study we tested the hypothesis that trigeminal nociceptive neurons are directly sensitized by lipopolysaccharide (LPS) isolated from an endodontic pathogen, Porphyromonas gingivalis. In vitro studies conducted with cultures of rat trigeminal neurons demonstrated that pretreatment with [PS produced a significant increase in the capsaicin-evoked release of calcitonin gene-related peptide (CGRP) when compared with vehicle pretreatment, thus showing sensitization of the capsaicin receptor, TRPV1, by LPS. Furthermore, confocal microscopic examination of human tooth pulp samples showed the colocalization of the LPS receptor (toll-like receptor 4, TLR4) with CGRP-containing nerve fibers. Collectively, these results suggest the direct sensitization of nociceptors by LPS at concentrations found in infected canal systems as one mechanism responsible for the pain associated with bacterial infections. (J Endod 2011;37:45-48)3714548UTHSCSANIH [DE015576]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)NIH [DE015576]CNPq [PDE 200880/2005-5]