Chapter 49 - Organophosphorus-Induced Delayed Neuropathy

Abstract

This chapter focuses on the neuropathy caused by exposure to organophosphorus (OP) compounds used as insecticides. Organophosphorus-induced delayed neuropathy (OPIDN) is a generally progressive, irreversible disorder that causes clinical manifestations, which appear days to weeks after humans and certain species of animals are exposed to OP compounds that can essentially irreversibly inhibit most of the available neuropathy target esterase (NTE, neurotoxic esterase). The severity of OPIDN, as indicated by clinical and anatomical manifestations, depends on species and age of test animals and extent of NTE inhibition. Chickens have proven the most sensitive test species. OPIDN is manifest clinically by ataxia and weakness progressing to paralysis, associated with bilateral degeneration of distal and terminal regions of long myelinated nerve fibers. The neuropathy can be prevented by pretreatment with NTE inhibitors; yet these same compounds promote OPIDN when given after a neuropathy-inducing OP compound. Although the precise mechanism of OPIDN has not been determined, there appears to be a role for calcium, as calcium blockers ameliorated the effect, and changes on CaM kinase II activity and cytoskeletal protein phosphorylation appear after administration of neuropathy-inducing OP compounds. Recent studies indicate that NTE purification is imminent, and that neuropathy-inducing OP compounds and their effects on NTE can be studied in cultured cells.