title: Lipopolysaccharide from Porphyromonas gingivalis sensitizes capsaicin-sensitive nociceptors.
abstract: 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 LPS 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.
authors.affiliation: Department of Endodontics, Piracicaba School of Dentistry, State University of Campinas, Piracicaba, SP, Brazil.
authors.forename: Caio Cezar Randi
authors.initials: CC
authors.lastname: Ferraz
authors.forename: Michael A
authors.initials: MA
authors.lastname: Henry
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Hargreaves
authors.forename: Anibal
authors.initials: A
authors.lastname: Diogenes
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000382:microbiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000382:microbiology / Q000503:physiopathology*; D016966:Porphyromonas gingivalis / Q000472:pathogenicity; D011671:Pulpitis / Q000150:complications / Q000382:microbiology; D051381:Rats; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000166:cytology / Q000187:drug effects
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D015740:Calcitonin Gene-Related Peptide