DFP-induced elevation of strength-duration threshold in hen peripheral nerve

Previous research has indicated that organophosphorus agents which induce a delayed neuropathy also elevate the strength-duration threshold during the progression of the neuropathy. To establish further the correlation between strength-duration changes and delayed neuropathy, the purpose of the present study was to investigate the biochemical and electrophysiological effects of two additional agents: diisopropylflourophosphate (DFP) and phosphonothioc acid, methyl-[2-(dimethylamino)-ethyl]O-ethyl ester (VX). DFP-treated hens exhibited clinical signs of toxicity at the time of electrophysiologic recording and biochemical analysis. DFP treatment also resulted in significantly elevated thresholds of the strength-duration curves of both the sciatic and tibial nerves. The VX-treated animals exhibited no clinical signs, despite aggressive dosing, and there were no significant changes in the electrophysiologic characteristics (conduction velocity, relative refractory period, strength-duration threshold) of either peripheral nerve. Acetylcholinesterase activities of the brain and skeletal muscle were significantly reduced in the VX- and DFP-treated hens, whereas creatine phosphokinase activities in these tissues were unaffected. These results are consistent with the view that elevation of the strength-duration threshold in peripheral nerves is among the earliest indicators of organophosphorus-induced delayed neuropathy.