Dexamethasone effects on Nav1.6 in tooth pulp, dental nerves, and alveolar osteoclasts of adult rats

Abstract

Dexamethasone causes extensive physiologic reactions including the reduction of inflammation and pain. Here, we asked whether it also affected dental or periodontal cells or dental innervation by altering voltage-gated sodium channel Na(v)1.6 immunoreactivity (IR) or neural synaptophysin. Daily dexamethasone (0.2 mg/kg) given for 1 week to rats caused 12-fold increased intensity of Na(v)1.6-IR in dendritic pulpal cells of normal molars and incisors compared with vehicle treatment. These cells also co-localized monocyte (ED-1) or dendritic cell (CD11b/Ox42) markers, and their location in molars expanded during dexamethasone treatment to include deeper pulp. Furthermore, dexamethasone caused a 10-fold decrease in the number of Na(v)1.6-immunoreactive multinucleate osteoclasts along the alveolar bone of molar root sockets. No changes occurred for neural Na(v)1.6 at axonal nodes of Ranvier, even though IR for calcitonin gene-related peptide was greatly decreased, as expected, and neural synaptophysin-IR was decreased 59% by dexamethasone. At 4 days after tooth injury, pulpal vasodilation and increased Na(v)1.6-immunoreactive pulp cells were similar for all groups. Thus, dexamethasone changes dental pulp cell and alveolar osteoclast Na(v)1.6-IR in normal teeth, but different mechanisms occur after tooth injury when tissue reactions were similar for dexamethasone- and vehicle-treated rats. Steroid-induced alterations of dental pain and inflammation coincide with altered exocytic capability in dental nerve fibers as shown by synaptophysin-IR and with altered pulp cell Na(v)1.6-IR and osteoclast number, but not with any changes in Na(v)1.6-IR for nodes of Ranvier in myelinated dental axons.

Unmyelinated nerve fibers in the human dental pulp express markers for myelinated fibers and show sodium channel accumulations

“…This antibody shows a wide range of species reactivity including humans [17,47]. The staining pattern seen in the current study is consistent with that seen previously [17,47,48]. …”

Ion Channels Involved in Tooth Pain

“…Since expression of VGSCs is an important property of excitable cells, the demonstration of Na V 1.6 expression in non-neuronal pulpal cells, such as pulpal immune cells, dendritic pulpal cells, and odontoblasts [29], has gathered a robust interest. In addition, electrophysiology, immunohistochemistry, RT-PCR, and in situ hybridization of odontoblasts differentiated from human dental pulp explants has revealed the expression and functionality of Na V 1.1, Na V 1.2, and Na V 1.3 [28].…”

“…In addition, voltage-gated and ligand-gated ion channels take important roles in tooth pain. Not only are various types of voltage-gated ion channels expressed in the trigeminal sensory nerve on common nerve cells, but they are also expressed in odontoblast cells [22,28,29,30,31,32]. Previous studies have indicated that small molecules, such as adenosine 5′-triphosphate (ATP), and their ionotropic receptors, the P2X family, play an important role in the sensory system for tooth pain [19,33,34,35].…”

Dexamethasone-induced up-regulation of two-pore domain K+ channel genes, TASK-1 and TWIK-2, in cultured human periodontal ligament fibroblasts

“…Dexamethasone (Dex) causes extensive physiologic reactions including the reduction of inflammation and pain (Byers et al 2009). Dex is also known to enhance the osteoblastic phenotype in osteogenic cells, decrease collagenase expression, increase the PTH-mediated cAMP response, including PDL fibroblasts (Hayami et al 2007;Hakki et al 2009).…”