Kv1.4 Subunit Expression is Decreased in Neurons of Painful Human Pulp

Quantitative Ultrastructural Analysis of the Neurofilament 200–Positive Axons in the Rat Dental Pulp

“…It is difficult to inhibit impulse transmission by using anesthesia on the inflamed pulp (30). Recent studies have reported that expression of tetrodotoxin-resistant voltage-gated Na channels NaV1.8 and NaV1.9 increase and voltage-gated K channel Kv1.4 decreases in the inflamed pulp, contributing to increase in neuronal excitability and sometimes to failure of local anesthetics (31)(32)(33). Application of blockers for these Na and K channels can also block inflammatory pain through blocking the propagation of nociceptormediated action potential.…”

Expression of Metabotropic Glutamate Receptor mGluR5 in Human Dental Pulp

“…The expression of TRPV1 in a large number of the mGluR5+ pulp afferents supports this notion and suggests that the increase in the TRPV1 response may be downstream from the activation of mGluR5 within the same axons. With the activation of mGluR5 at the site of inflammation, changes in the expression of various ion channels on pulpal afferents may lead to hyperexcitability of pulpal neurons and hyperalgesia during pulpal inflammation (21)(22)(23). mGluR5+ was expressed strongly by axons that branched extensively in the peripheral pulp, but the immunostaining was weaker and the immunopositive axons branched less in the central portion of coronal pulp and in the radicular pulp.…”

Expression of Nav1.9 Channels in Human Dental Pulp and Trigeminal Ganglion

“…Specimens were prepared according to methods described elsewhere (9,11). Briefly, after extraction, teeth were immediately placed in vials of 4% paraformaldehyde (PF) in 0.15 mol/L phosphate-buffered saline (PBS) overnight at 4°C.…”

“…Antisera against neurofilament has been applied and accepted for immunohistochemical localization of human dental pulp axons (9,11,23). Sections were rinsed in PBS and then incubated with immunoglobulin G antibodies (donkey anti-chicken CY2 [fluoresces and illustrated in green] to localize neurofilament antibody donkey anti-mouse tetramethylrhodamine [fluoresces and illustrated in red] to localize Nav1.9 antibody; all from Jackson ImmunoResearch Laboratories; West Grove, PA) at 1:300 in 4% NDS and 0.1% TX in PBS for 1 hour at room temperature.…”

“…Pulpal inflammation induces alterations in primary afferent neurons, resulting in increased excitability (4,5), which play roles in the generation of allodynia and hyperalgesia (6). Hyperexcitability of primary afferent neurons is a result of both an inflammatory reaction occurring at the site of injury and changes occurring in ionic channels and currents carried across the neuronal membrane (7)(8)(9)(10)(11).…”