Release of sensory neuropeptides after stimulation of afferent nerve fibers has previously been shown to induce vasodilation and increased vascular permeability in the dental pulp, a condition recognized as neurogenic inflammation. In the present study a possible role for the sensory neuropeptides in transendothelial migration of immunocompetent cells was investigated. The dental pulp is an isolated tissue densely innervated with sensory fibers containing neuropeptides, and following electrical stimulation of the crown, the effect on pulpal blood flow and immunocompetent cells can be studied in a noninvasive model. A laser Doppler flowmeter was used to measure relative changes in pulpal blood flow during long-lasting intermittent stimulation of innervated and denervated rat first molars. In the innervated teeth, stimulation promptly increased pulpal blood flow by on average 45% at the start of the experiment, whereas almost no blood flow increase was recorded after 4 to 5 h stimulation. Surgical sectioning of the inferior alveolar nerve abolished blood flow increase upon stimulation. After stimulation, a quantitative analysis of CD43+, CD4+, CD11+, and I-A antigen-expressing cells was performed, and the effect of stimulation on calcitonin gene-related peptide (CGRP)-immunoreactive and substance P (SP)-immunoreactive (IR) nerve fibers was studied. Immunohistochemistry was performed by the avidin–biotin peroxidase method. Stimulation resulted in an almost complete depletion of CGRP- and SP-IR nerve fibers in the first molar pulp, whereas nerve fibers in the gingiva and neighboring teeth were unaffected. A significant increase in the number of CD43+cells was found in the innervated tooth after stimulation compared to the stimulated denervated (P<0.01) and unstimulated control (P<0.05) first molars. For I-A antigen-expressing cells a significant increase (P<0.05) was found between the innervated stimulated and unstimulated control, but not between the innervated and denervated stimulated first molars. Hence, from the present experiment it is concluded that the pulpal nerves participate in and facilitate transendothelial migration of CD43+cells during acute neurogenic inflammation.
Read full abstract