The voltage-gated sodium channel Nav1.8, expressed predominantly in small- and medium-sized neurons, has been shown to increase following inflammation and may play a pivotal role in the development of chronic pain. The aim of the present study was to examine the expression of sodium channel subtype Nav1.8 in non-carious, carious non-painful and carious painful human permanent teeth, and identify any association between its expression, clinical symptoms and response to thermal stimulus.
Methods:
Mandibular first permanent molar teeth were extracted from children under general anaesthesia, and categorised into three groups according to the degree of caries and reported symptoms of pain: non-carious (n=11), carious non-painful (n=11) and carious painful (n=11). The teeth were prepared and processed for indirect immunofluorescence using primary antibodies raised against Nav1.8 and PGP 9.5, a general neuronal marker. Antibody binding was visualized using fluorescent microscopy and image analysis employed to quantify the percentage area of PGP 9.5 immunoreactive tissue also labelled positively for Nav1.8 in three regions of the tooth pulp: the pulp horn, the subodontoblastic plexus and the mid-coronal region.
Results:
Immunoreactivity for Nav1.8 was present within the three sampled regions of the tooth pulps, in all three groups analysed, and dual labelling immunohistochemistry revealed Nav1.8 to be co-localised with PGP 9.5 labelled nerve fibres. Quantitative image analysis revealed that levels of Nav1.8 were significantly higher (ANOVA, p=0.013) in carious painful tooth pulps compared to carious non-painful specimens, in the pulp horn region. Furthermore in the patients reporting experiences of pain, there was a significant negative correlation between the level of expression of Nav1.8 and the Visual Analogue Score (VAS) recorded (p<0.005).
Conclusions:
These data provide further evidence that changes in expression of Nav1.8 are important in the development of inflammatory-induced pain and may be a potential target for novel therapeutics for chronic pain.