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

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 corresponding molecular changes would occur in nociceptive neurons coding for pain in skin, muscle or vasculature. Following a 30 day exposure to neurotoxicantsPB, we observed molecular dysfunctions in membrane Kv proteins Kv7, KDR that persisted at least 4 weeks after exposure had ended. K channel protein malfunctions were limited to neurons we have attributed to the vascular system. Neurons that innervate skin and muscle were not affected. The physical location of vascular nociceptive neurons renders them most exposed to concentrations of circulating neurotoxicantsPB as well as to any blood borne secondary influences endocrine, immune these agents might induce. As a result, vascular nociceptors could be the first.