A significant portion of somatosensory C-fibers are chemosensitive and subserve our ability to detect chemical (often noxious) stimuli, chemesthesis. C fibres typically express one or more subtypes of specific ligand-gated receptors both in their peripheral terminals as well as along their parent axons. The physiological role of axonal chemosensitivity is diverse, serving a protective function against chemical toxins on the one hand and a more nuanced modulatory role on the other. In this context, we have recently shown that peripheral glia can influence the excitability of C fibres via actis via GABA-A receptors. Glial derived neurosteroids and GABA can modulate axonal excitability in a subpopulation of C-fibers and this effect is absent in mice lacking the beta3 GABA-A subunit. 

Assessment of axonal chemosensitivity is also a valuable tool to assess the efficacy and pharmacological profile of new compounds, especially those targeted to voltage gated channels. For this we use the ingenious QTRAC software to track average axonal threshold. This technique allows inferences about changes in axon number, membrane potential and is ideally suited to rapidly screen pharmacological agents.