Application of capsaicin on oral mucosa induces pain and neurogenic vasodilatation in adjacent gingival tissues. Pain-associated inflammatory reactions have been shown to provoke expressions of several pro-inflammatory mediators. Matrix metalloproteinase (MMP)-8 is the major tissue destructive protease in gingival crevicular fluid (GCF). In this study, we investigated whether stimulation of alveolar mucosa by capsaicin would induce changes on GCF MMP-8 levels in healthy human volunteers. Capsaicin (3%) moistured filter paper (4 x 1.5 mm) was applied unilaterally to the buccal alveolar mucosa between the permanent upper first/second incisor. The GCF samples were collected from the stimulated tooth and from several other incisors in upper and lower jaw. The MMP-8 levels in GCF samples were determined by Western immunoblotting and immunofluorometric assay. Capsaicin stimulation of the alveolar mucosa induced significant elevations on MMP-8 levels in GCF of the adjacent teeth. This capsaicin-evoked MMP-8 elevation lasted several minutes after the end of stimulation. During the experiments, there were no marked changes on MMP-levels in GCF of distantly situated teeth. Capsaicin did not cause any changes on systemic HR and BP levels. These results indicate that capsaicin, causing a local neurogenic vasodilatation in gingiva, is also capable of triggering the release of destructive proteases such as MMP-8 in GCF of the adjacent teeth.