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Persistent Neural Membrane Protein Misregulation Following Neurotoxicant Exposure

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Annual rept. 30 Sep 2013-29 Sep 2014

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Cellular, molecular and behavioral experiments were conducted in rats to determine the molecular basis of a widespread chronic pain that is frequently reported in veterans of the 1991 Gulf War. Behavioral studies examined whether chronic exposure to insecticides chlorpyrifos, permethrin and a nerve gas prophylactic pyridostigmine bromide could produce a delayed and persistent myalgia and arthralgia. Following a 60 day exposure to these Gulf War chemicals, we observed an increase in resting behaviors that persisted for 12 weeks after exposures had ceased. Muscle and vascular nociceptive neurons that were harvested from these animals, at 8 and 12 weeks post-exposure, exhibited broad alterations in the physiology of Kv ion channels Kv7 and other KDR channel proteins and Nav1.9 that were consistent with increased cellular excitability at the 12 week observation period. An imbalance between Kv7 and Nav1.9 could prove to be the basis for a chronic pain condition sourced from a vulnerable subset of vascular and muscle nociceptors. Because these ion channels are widely expressed throughout the nervous system, maladaptations in their physiology could contribute to the development of a variety of sensory, motor, cognitive and autonomic symptoms associated with Gulf War Illness.

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  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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