Effect of the sensory neuropeptide antagonists h-CGRP (8–37) and SR 140.33 on pulpal and gingival blood flow in ferrets

Abstract

In a previous study, it was concluded that the neuropeptides calcitonin gene-related peptide (CGRP) and substance P are released during resting conditions in the (exposed) ferret dental pulp, contributing to a basal vasodilator tone in the pulpal vessels. In order to exclude the possibility that the method used elicited axon reflexes, which might be responsible for neuropeptide release, the present study was designed without pulp exposure. Non-invasive laser–Doppler flowmetry was used to measure the effects of intra-arterial infusions of the antagonists h-CGRP (8–37) and SR 140.33 (neurokinin 1-receptor antagonist) on pulpal and gingival blood flow before, during and after electrical tooth stimulation. Infusions of h-CGRP (8–37) reduced the basal blood flow in the pulp by 31.4±5.2% ( p<0.001) and in the gingiva by 22.6±4.8% ( p<0.05). A further significant decrease in basal blood flow was measured in both pulp and gingiva following SR 140.33 administration. The reduction in blood flow was 16.9±1.9% ( p<0.005) in the pulp and 19.3±5.6% ( p<0.05) in the gingiva. The systemic arterial pressure remained unchanged both during and after the periods of infusion. Tooth stimulation before the antagonist infusion significantly increased the pulpal blood flow by 71.9±15.3% ( p<0.005). Infusion of h-CGRP (8–37) greatly reduced this electrically induced vasodilatation, indicating that CGRP is the principal factor responsible for the vasodilatation observed after tooth stimulation. This study confirms the previous finding that a resting vasodilator tone due to the release of CGRP and SP exists in the ferret dental pulp. It is concluded that spontaneous, basal release of the neuropeptides CGRP and substance P exists both in dental pulp and gingiva in the ferret.