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Neurovascular and Autonomic Dysfunction Associated with Gulf War Illness Pain

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Technical Report,30 Sep 2016,29 Sep 2017

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University of Florida Gainesville United States

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Soldiers returning from the 1991 Persian Gulf War suffered from a variety of cognitive, motor, sensory and autonomic symptoms. We have shown that a 4 week exposure to DEET, chlorpyrifos, permethrin and PB produced pain-like signs and chronic vasodilation in rats that persisted up to 24 weeks after exposure. The onset and extent of these signs were increased by inclusion of DEET in the exposure protocol. The appearance of pain signs were dependent on the inclusion of anticholinesterases chlorpyrifos or PB. Exclusion of either clorpyrifos or PB prevented the development of behavioral deficits and autonomic maladaptations Flunker et al., 2017. We had previously demonstrated that nociceptors from rats exhibiting pain behaviors exhibited defects in the activity of nociceptor ion channels Kv7 Nutter et al., 2015 NaV1.9 Cooper et al., 2014. We have now replicated the effect on NaV1.9 and demonstrated that it was up-regulated up to 16 weeks after exposures had ended. Using the demonstrated capacity of PB to control the appearance of pain signs we have further shown that deficits in Kv7 did not vary with pain signs exhibited in PB exposed or non-exposed rats Flunker et al., 2017, moreover, they did not persist past 12 weeks post-exposure. Therefore, shifts in Kv7 activity were not fundamental to the development or maintenance of pain in our model. Studies examining the capacity of FDA approved drugs to manage pain signs in exposed rats were partially successful. During a 4 week treatment with the Kv7 opener Retigabine 1200 mgkgday, rat pain signs were significantly improved, however, pain signs rapidly reappeared once treatments ceased. Given the function of Kv7, the capacity of a Kv7 active drug to improve pain signs, even though Kv7 ion channels were not directly involved in the pathophysiology of GWI pain, was not unexpected nor implausible. Yet it is not likely that targeting this ion channel would constitute a broad or permanent cure for symptoms of GWI.

Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology
  • Pharmacology

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