Involvement of substance P but not nitric oxide or calcitonin gene-related peptide in neurogenic plasma extravasation in rat incisor pulp and lip

Abstract

The possible involvement of the neuropeptides substance P and calcitonin gene-related peptide (CGRP) in the development of neurogenic plasma extravasation in the lower lip, gingiva and incisor pulp was examined in anaesthetized rats by means of the Evans blue method and by using newly developed blockers of substance P (CP-96,345) and CGRP (CGRP8-37). Electrical stimulation of the inferior alveolar nerve (15 V, 2 ms, 10 Hz) for 5 min significantly increased the Evans blue content of the ipsilateral lip, gingiva and pulp by 60 (p < 0.01), 62 (p < 0.01) and 92% (p < 0.05), respectively (n = 8). Pretreatment with CP-96,345 (total dose: 1.5 mg/kg, intravenously) counteracted the dye leakage in the lip and pulp but not in the gingiva (n = 6). The inactive enantiomer (CP-96,344, 1.5 mg/kg, n = 8) or the nitric oxide synthesis inhibitor (N omega-nitro-L-arginine methyl ester hydrochloride, 10 mg/kg, n = 7) did not reduce the stimulation-induced dye extravasation in any of the tissues. Pretreatment with CGRP8-37 (0.3 mg/kg, n = 7) did not significantly influence the development of neurogenic extravasation in the lip and incisor pulp, but it slightly attenuated extravasation in the gingiva. The results indicate that the afferent nerve-induced dye extravasation in the lip and pulp, but not in the gingiva, is to a large extent mediated by substance P acting via neurokinin-1 receptors. There was no evidence for an involvement of nitric oxide or CGRP in neurogenic extravasation in rat incisor and lip.