Neurovascular and Autonomic Dysfunction Associated with Gulf War Illness Pain
Technical Report,30 Sep 2015,30 Dec 2017
FLORIDA UNIV GAINESVILLE GAINESVILLE United States
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It has been reported that exposure to DEET was highly correlated with the development of GWI pain. We examined the consequences of adding DEET to an exposure protocol composed of permethrin, chlorpyrifos and pyridostigmine bromide PB on the development of pain behaviors and autonomic dysfunction in a rat model of GWI. It was demonstrated that the development and degree of pain behaviors were greatly accelerated and magnified in the DEET augmented protocol. These pain behavior signs were accompanied by peripheral chronic vasodilation. However, the appearance of any pain behaviors or chronic vasodilation were wholly dependent on the presence of anticholinesterases PB, chlorpyrifos in the exposure set. A series of cellular and molecular studies indicated that the pathophysiology of this pain was due to maladaptations to ion channel Nav1.9 and muscarinic receptors linkages to Kv7 and TRPA1 in vascular and muscle nociceptors. The Kv7 opener, Retigabine, significantly reversed pain signs in rats 9-13 weeks following exposure. The capacity to reverse an established chronic myalgia in a rat model suggests thatKv7 openers could be a promising treatment for GW veterans suffering from chronic pain.
- Medicine and Medical Research
- Anatomy and Physiology