Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity

The expression of GABA(A) receptors and the effects of GABAA receptor agonists on the response properties of tongue afferent fibres were investigated in female rats to determine if peripheral GABA receptors might be a target of topical benzodiazepines when used for pain relief in burning mouth syndrome patients.

Nerve fibres in tongue sections from six female rats were identified using protein gene product 9.5, and the co-expression of the γ subunit of GABAA receptor and substance P assessed in the nerve fibres. In vivo extracellular recordings of trigeminal ganglion neurons that innervate the tongue were undertaken in 27 anesthetised female rats and their responses to mechanical and thermal stimulation characterised before and after topical application of GABA, the GABA(A) receptor selective agonist muscimol or vehicle control.

The vast majority of tongue nerve fibres examined (95%) expressed the γ subunit of GABA(A) receptor. Bath application of muscimol, but not GABA, significantly increased the mechanical thresholds of tongue afferent fibres compared to vehicle, but only after the tongue had been heated with 60°C water.

GABA(A) receptors are present on tongue nerve fibres and their activation alters the mechanical sensitivity these fibres. These findings suggest that topical application of benzodiazepines to the oral mucosa may decrease pain in burning mouth syndrome through a local action on peripheral GABAA receptors.