Use of the biventer cervicis nerve-muscle preparation to detect early changes following exposure to organophosphates inducing delayed neuropathy

Fundam Appl Toxicol. 1990 Jul;15(1):108-20.

Abstract

Indices of organophosphorus (OP)-induced delayed neuropathy (OPIDN) in the hen model have traditionally been restricted to the early inhibition of neuropathy target esterase (NTE) and ataxia with associated pathological changes in hind limb peripheral nerve which occur more than 7 days after OP exposure. The biventer cervicis nerve-muscle preparation was used to evaluate OPIDN in adult hens at various time periods after treatment with either the protoxicant tri-o-tolyl phosphate (TOTP), 360 mg/kg po, or the active congener phenyl saligenin phosphate (PSP), 2.5 mg/kg im. NTE activity was 21 and 48% of control for TOTP and PSP, respectively, 4 days after administration. Clinical signs were notable by 10 days and progressed in severity to paralysis by 21 days. Partial clinical recovery was evident at 37 days. Denervation hypersensitivity of biventer cervicis muscle to acetylcholine (ACh) was evident as early as 4 days following TOTP or PSP treatment. The sensitivity to ACh was greatest 21 days after OP administration, with partial recovery at 37 days. Strength-duration curves (SDC) of preparations from OP-treated hens showed an increase in excitability thresholds and elevated rheobase with shorter chronaxie than did preparations from controls as early as 4 days following treatment with either compound. SDC at 37 days indicated partial reinnervation. Peripheral nerve myelinated fiber degeneration and regeneration consistent with these physiological changes was seen on histopathological examination. This study suggests that the biventer cervicis nerve-muscle preparation may prove useful for detection of functional and morphological changes that occur during the interval between NTE inhibition and appearance of clinical deficits.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Ataxia / chemically induced
  • Ataxia / physiopathology
  • Carboxylic Ester Hydrolases / antagonists & inhibitors
  • Chickens
  • Electrodes
  • Electrophysiology
  • Female
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / physiopathology
  • Neuromuscular Junction / drug effects*
  • Organophosphorus Compounds / toxicity*
  • Tritolyl Phosphates

Substances

  • Organophosphorus Compounds
  • Tritolyl Phosphates
  • phenylsaligenin cyclic phosphate
  • Carboxylic Ester Hydrolases
  • neurotoxic esterase
  • Acetylcholine
  • tri-o-cresyl phosphate