Synergistic Actions of Pyridostigmine Bromide and Insecticides on Muscle and Vascular Nociceptors.

摘要

We examined whether chronic exposure to combinations of two neurotoxicants (chlorpyrifos and permethrin) with pyridostigmine bromide (PB) could produce a delayed neuropathic pain condition in rats; and whether corroccur in nociceptive neurons coding for pain in skin, muscle or vasculature. Following a 60 day exposure to neurotoxicants/PB esponding molecular changes would (NTPB), we observed molecular dysfunctions in membrane Kv (Kv7) and Nav (Nav1.8, Nav1.9) proteins that persisted 8 weeks after exposure had ended. Functional changes (spontaneous activity, action potential duration) were also documented. Most of the maladaptations were present in vascular nociceptors. The physical location of vascular nociceptive neurons renders them most exposed to concentrations of circulating neurotoxicants/PB as well as to any blood borne secondary influences (endocrine, immune) these agents might induce. As a result, vascular nociceptors could be the first nervous system component damaged by neurotoxicants/PB. An imbalance between Kv7 and other Na+ channel proteins (Nav1.9) could prove to be a basis for a chronic pain condition sourced from a vulnerable subset of vascular nociceptors. A resulting neurovascular reflex dysfunction could cause widespread pain and also contribute to the development of CNS symptoms that have been identified in Gulf War veterans.