Tumor Necrosis Factor Receptor I Expression in Inflamed Human Pulps

Objectives: Tumor Necrosis Factor α (TNFα), a pro-inflammatory cytokine, plays an important role in the pathogenesis of several inflammatory conditions including pulpitis and periradicular periodontitis (Pezelj-Ribaric et al. 2002; Wang et al. 1997). Levels of endogenous TNFα are correlated with pain reports in patients with orofacial pain such as temporomandibular dysfunction (Schafer et al. 1994). These and other studies support the hypothesis that TNFα mediates pain in humans. TNFα exerts its effects through its two known receptors TNF receptor I (TNFRI) and receptor II (TNFRII). In this study, we evaluated the hypothesis that neuronal expression of TNFRI is increased in pulps extripated from teeth with irreversible pulpitis as compared to pulps from normal, asymptomatic teeth.

Methods: Teeth were collected from subjects undergoing extraction of their normal, asymptomatic wisdom teeth (n=5) or painful molar teeth diagnosed with irreversible pulpitis (n=9). All samples were identically processed with the indirect immunofluorescence method, and images were obtained with confocal microscopy using standardized gain settings. The immunofluorescence intensities and areas occupied by TNFRI within N52/GAP43-identified nerve fibers were quantified with NIH ImageJ software and statistical significance was evaluated with Student's t-test.

Results: The expression of TNFRI was significantly increased in neuronal axons innervating the pulp horns of inflamed pulps as compared to axons innervating normal horns (p<0.05), whereas there was no difference in the radicular pulp.

Conclusion: We conclude that the localized upregulation of axonal TNFRI may contribute to the development of pain associated with pulpal inflammation. These data suggest that drugs which inhibit TNFα may serve as novel analgesics in the management of pain associated with irreversible pulpitis.

This work was supported by NIDCR, Grant #DE 14318 for the CO STAR Program, NIH K23 DE 14864, and NIH DE 015576