Relative refractory period as a measure of peripheral nerve neurotoxicity

A method is presented for converting the relative refractory period to a linear form which can be used for quantifying changes in peripheral nerve conduction and membrane excitability. Since the relative refractory period is very consistent in nerves taken from animals of a given age, strain, and size, small alterations due to exposure by neurotoxic agents can readily be detected. In the present study rat sciatic nerves exposed to phenol developed a peripheral neuropathy which was detected by an increased relative refractory period. Diisopropylfluorophosphate (DFP), another neuropathic agent, produced a shift in the relative refractory period which was also consistent with the time course of its known neurotoxicity. On the other hand, acrylamide did not change the relative refractory period although the rats exhibited deficits when measured behaviorally (roto-rod and inclined screen tests). This observation is consistent with the view that the acrylamide toxicity initially affects nerve endings and spares the nerve axon. Erythrosin B, an agent which enhances nerve excitability, produced a shift in the relative refractory period which indicated that the nerve was less refractory. These examples point to the value of the relative refractory period as an index of the extent and type of neurotoxicity induced by agents which affect peripheral nerve axons, and suggest that this method may be useful in determining the mechanism of action of neurotoxic agents.