Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 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 Nav1.7 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 Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 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 Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS

Sensory purinergic receptor P2X(3) is elevated in burning mouth syndrome

Recent studies show that P2X3 may play a role in neuropathic pain, including orofacial pain. Burning mouth syndrome (BMS) is a chronic neuropathic pain condition affecting 0.6–12% of post-menopausal women in the Western world. This study evaluates, for the first time, P2X3 immunoreactivity levels in lingual mucosa in BMS patients. Patients diagnosed with BMS (n = 9) in accordance with International Association for the Study of Pain criteria and patients attending for wisdom tooth removal (n = 10, controls), were involved in this study. A pain history and score was recorded on a visual analogue scale (VAS) prior to obtaining a lingual biopsy. Immunohistochemistry and image analysis were used to quantify submucosal nerve fibres expressing P2X3 and the structural marker neurofilaments. P2X3 positive fibres were significantly increased in BMS compared with controls (p = 0.024). In contrast, neurofilament-staining fibres were reduced in BMS, and when expressed as a ratio of the neurofilament percentage area, there was a trend for an increase of P2X3 positive fibres in the BMS group. Increased P2X3 immunoreactivity in the trigeminal sensory system may play a role in the symptoms observed in BMS. P2X3 may therefore be a therapeutic target for treating BMS and trigeminal neuropathic pain