Sodium channel Na(v)1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

Background: Voltage gated sodium channels Na(v)1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives: To study Na(v)1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS), considered a neuropathic orofacial pain disorder. Methods: Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5) and controls (n = 12), and the other patients with BMS (n = 7) and controls (n = 10). BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS). Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Na(v)1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results: There was a significantly increased visual intensity score for Na(v)1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Na(v)1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Na(v)1.7 in the painful pulp group. Na(v)1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion: Na(v)1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Na(v)1.7 channel blockers should prioritise dental pulp pain rather than BMS.