Opioid System is Prominently Expressed in Inflamed Human Dental Pulp

The use of the tooth as a model system for studying pain mechanisms is well established.  Pulpitis is typically attributed to inflammatory mechanisms secondary to a bacterial invasion of the pulp.  Bacterial invasion results in immune responses and although the pain-promoting effects of immune cells are well known, other evidence suggests pain relief by the peripheral release of endogenous opioids from immune cells.  Although opioid-containing immune cells have been described in the inflamed rat dental pulp, similar studies in humans are lacking.  Objectives: The aim of this study was to characterize the effect of inflammation on the endogenous opioid system (peptides and receptors) within the human dental pulp.  Methods: Normal and inflamed human dental pulp sections were stained with antibodies against opioid peptides (β-endorphin/met-enkephalin/dynorphin A), or their receptors (mu/delta/kappa) with the indirect immunofluorescence method and evaluated with confocal microscopy.  Expressions were characterized within N52/PGP9.5-identified axons, and the expression of β-endorphin was further characterized within specific immune cells with CD3 (T-lymphocytes), CD14 (monocytes/macrophages), CD23 (B-lymphocytes) and SPM250 (granulocytes) antibodies.  Results: All opioid peptides were minimally expressed within normal specimens, but were prominently expressed within immune cells in inflamed specimens.  Use of immune cell-specific antibodies showed prominent β-endorphin expression within B-lymphocytes and macrophages, less so in T-lymphocytes and rare in granulocytes.  All three opioid-receptors showed minimal expression in normal specimens but with a prominent expression within immune cells and in nerve fibers in inflamed specimens.  Conclusions: Opioid peptides and receptors are highly expressed within the inflamed human dental pulp.  Activation of the endogenous opioid system provides a potent method to modify pulpitis pain severity and may contribute to the varying pain levels experienced in patients with pulpitis.