ATX-II was originally isolated from the venom of the sea anemone Anemonia sulcata and is characterized as a potent sodium channel activator. Recently specific sodium channel subtypes were linked to human pain and detailed knowledge of their modulation may prove advantageous for the development of new pain treatments.

Question: 

Does ATX-II affect resurgent and persistent sodium currents in large and small sensory dorsal root ganglion neurons (DRGs)? Does ATX-II affect peripheral A- and C-fibers?

Methodology: 

We investigated the effects of ATX-II on voltage-gated sodium currents in small and large diameter DRGs using whole-cell voltage-clamp recordings. We assessed excitability changes of murine A- and C-fibers by compound and single-fiber action potential recordings. In healthy human volunteers thermal and mechanical sensitivity as well as pain ratings before and after intra-cutaneous injections of ATX-II were assessed. Activation of C-fibers was examined indirectly by visualizing the axon reflex erythema with a Laser Doppler Imager.

Results: 

ATX-II increased resurgent and persistent currents in large diameter DRGs, but failed to influence small diameter DRGs. Accordingly, ATX-II enhanced stimulus evoked excitability only in A-fibers whereas C-fiber excitability is unaffected by the toxin. These results suggest that ATX-II exerts a selective effect on A-fibers. In humans intra-cutaneous injection of ATX-II produced pricking pain and altered mechanical sensitivity. However, no widespread axon reflex erythema could be found.

Conclusion: 

ATX-II selectively activates resurgent and persistent sodium currents in large diameter DRGs, which is likely to underlie a selective increase in excitability of A- but not C-fibers.