We assessed the capacity of ultrashort E-fields to activate rat cutaneous nociceptors. Experiments were
conducted in vitro on nociceptive neurons representing hairy skin and glabrous skin. Electrical and optical
recording methods were used to assess action potentials and membrane damage thresholds. Strength duration
(SD) curves were formed for E-field pulses from 500 μsec to 350 ns. There were no differences in the SD time
contant (taue (59 μsec) or ultrashort thresholds (129 V/cm at 350 ns) for hairy or glabrous skin nociceptors, for
nociceptors with distinct geometry or for nociceptors expressing different combinations of voltage sensitive
Na+ channels (TTXs and TTXr Nav) or hyperpolarization activated channels (HCN; IH). Subthreshold
activation was possible with high frequency pulsing at ultrashort durations (350 ns; 4,000 Hz). Relative to
single pulse thresholds, activation threshold could be reduced over 50% by high frequency burst trains (4,000
Hz; 1-40 msec). Nociceptors were not damaged by E-field activation. Irreversible membrane disruption
occurred at significantly higher field strength and varied by cell radius (3,266-4,240 V/cm, 350 ns, 40 Hz, 5
sec). Pulse frequency had no influence on acute membrane failure (10, 20, 40, 4,000 Hz; 5 sec).
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