Organophosphate-induced delayed neuropathy: an unresolved problem?

This work presents an analysis of recent publications devoted to delayed peripheral neuropathy caused by acute or chronic low-dose exposure to organophosphorus compounds (organophosphate-induced delayed neuropathy, OPIDN). The review discusses the clinical features of the disorder, characterized by a prolonged latent period between toxicant exposure and disease onset, and provides examples of both mass and suicidal poisonings. The morphological substrate of OPIDN includes swelling of distal segments of large axons, disruption of myelin sheath membranes, and subsequent degeneration of nerve fibers of the Wallerian type. The role of Schwann cells in axonal regeneration and the cellular and molecular mechanisms underlying axon–Schwann cell signaling are discussed. Major hypotheses regarding the noncholinergic mechanisms of OPIDN pathogenesis are presented. Special attention is given to the role of neuropathy target esterase as the principal molecular target of organophosphate action, the systemic inhibition of which, in combination with the “aging” reaction, initiates the development of OPIDN. In addition to neuropathy target esterase involvement, the potential role of other molecular targets of organophosphate action, oxidative stress, dysregulation of calcium homeostasis, and neuroinflammation is considered. Examples of experimental models of OPIDN, both in vivo and in vitro, are presented to illustrate approaches to studying its underlying mechanisms.