leukotriene-b4 and Pulpitis

Research conducted in the last 10 years has increased our knowledge on pain mechanisms substantially. Although many local tissue mediators, including neuropeptides, are known to exert pro-inflammatory effects, comparatively little is known about the actual tissue levels of these inflammatory mediators and their pharmacologic regulation. This article describes two new methods, clinical microdialysis and superfusion of dental pulp, which provide data on the pharmacology of peripheral neuropeptide and inflammatory mediator release. Collectively, these methods provide a biochemically based approach toward determining the mechanisms and management of orofacial pain.

Topics: Bradykinin; Calcitonin Gene-Related Peptide; Dental Pulp; Dinoprostone; Humans; Inflammation Mediators; Leukotriene B4; Microdialysis; Neuropeptides; Nociceptors; Pulpitis; Substance P; Toothache

Inflammation was induced in rat dental pulp by applying bacterial lipopolysaccharide (LPS). Extirpated tissue samples from inflamed pulps were incubated in vitro in a Krebs buffer containing Ca2+ ionophore A23187, and leukotriene (LT) B4 released into the medium was determined by radio-immunoassay. Production of LTB4 could be detected three to 24 h after the application of LPS and showed a maximum at 12 h. Histologically, marked infiltration of neutrophils, but not other leukocytes, was characteristically observed in the LPS-applied pulps, and the temporal change in neutrophil infiltration was almost parallel, but somewhat more delayed than LTB4 production. When BW755C, a dual inhibitor of cyclo-oxygenase and lipoxygenase, was given to the animals before the application of LPS, both the production of LTB4 and the number of infiltrated neutrophils were significantly decreased, whereas administration of indomethacin had no effect. These results suggest that LTB4 may be involved in neutrophil infiltration in pulpal inflammation. It was also suggested that a major early source of LTB4 in experimental pulpitis was leukocytes, primary neutrophils, because the synthesis of LTB4 in the inflammed pulp was diminished by depletion of circulating leukocytes with cyclophosphamide prior to the application of LPS.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Animals; Cell Movement; Cyclophosphamide; Dental Pulp; Indomethacin; Leukocyte Count; Leukotriene B4; Lipopolysaccharides; Male; Neutrophils; Pulpitis; Rats; Rats, Inbred Strains; Time Factors