Neuropeptide Y (NPY), together with certain of its receptors, exhibits significant changes in expression after peripheral tissue injury and is thought to modulate pain in animals. However, the clinical significance of the NPY system in modulating pain in humans is unknown.

Objectives: this study tested the hypothesis that a selective Y1 receptor agonist [Leu31,Pro34]-NPY (L,P-NPY) inhibits capsaicin-evoked release of immunoreactive substance P (iSP) from peripheral neuron terminals innervating normal and inflamed human periradicular tissues.

Methods: following informed consent, teeth with normal pulpal and periradicular tissues or teeth with necrotic pulps and chronic apical periodontitis were extracted, and the apical 6mm of each root was resected to isolate the connective tissue attached to the roots. The pulp canal systems were debrided to prevent measurement of any pulpal source of iSP. Tissues were pretreated with the Y1 agonist L,P-NPY (100 nM) or vehicle (modified Locke-Ringers) and then stimulated with capsaicin (50uM). Released iSP was measured by radioimmunoassay, and the data were analyzed by ANOVA. Test drugs did not interfere with the RIA.

Results: capsaicin evoked a 34% increase in release of iSP from normal periradicular tissues and a 61% iSP release from inflamed human periradicular tissues (p<.05) in a calcium-dependent, capsazepine-sensitive, dose-dependent manner. Pre-treatment with L,P-NPY significantly inhibited capsaicin-evoked iSP release from normal and inflamed tissues (p<.05 for both).

Conclusions: these results indicate that peripheral Y1 receptors inhibit the exocytotic activity of the capsaicin-sensitive class of nociceptors in both normal and chronically inflamed human tissue and suggest that NPY agonists may have analgesic activity in humans. Supported in part by R37 DE12888, F30 DE14326l.

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