Recent studies have demonstrated that pulpal pain can induce neurogenic inflammatory reactions in gingiva and the expression of pro-inflammatory neuropeptides in gingival crevicular fluid (GCF). Neuropeptides co-ordinate the activity of immuno-effector cells and may influence the secretion of matrix metalloproteinase (MMP)-8, the major tissue-destructive protease in GCF. With this background, we studied whether experimental pulpal pain can trigger changes in GCF MMP-8 levels. The molecular forms of MMP-8 in the GCF of stimulated and non-stimulated teeth were analyzed by Western immunoblot, and MMP-8 levels by quantitative immunofluorometric assay. Painful stimulation of the upper incisor provoked significant elevations in GCF MMP-8 levels of the stimulated tooth. Western immunoblot revealed elevations in both neutrophil- and mesenchymal-type MMP-8 isoforms. At the same time, the GCF MMP-8 levels of the non-stimulated teeth were not changed. Analysis of these data indicated that pulpal pain can induce local elevations in MMP-8 levels in GCF.