Optimizing Kv7 Channel Openers for Treatment of GWI Pain
Abstract
Gulf War Illness (GWI) affects nearly 200,000 Veterans of the 1991 Persian Gulf War. There is no effective treatment for this complex multisymptom disease. Chronic pain is a common component of GWI. The symptoms of GWI chronic pain are highly variable and include combinations of muscle, abdominal, joint, back, and headache pains. Following almost three decades of research, it is broadly accepted that GWI developed from simultaneous exposure to multiple insecticides, repellants, and anticholinesterase medications that were prescribed to or otherwise used by deployed Soldiers. The detailed pathophysiology of GWI is still unclear, but given the great variety of cognitive, motoric, and sensory symptoms that developed, it can be safely assumed that multiple, but related, pathologies contributed to the various symptom complexes that are reported. Our laboratory developed an animal model that replicates some of the symptoms of the chronic pain of GWI. Through this animal model, we identified several molecular targets in pain-sensing neurons, which appear to have been chronically altered following exposure to insecticides and repellants. Some of these molecular targets are known to contribute to other forms of chronic pain. Focusing on these target molecules, were able to show that treatment with certain Food and Drug Administration (FDA)-approved compounds, known as KVOs, modified their activity in a manner that could temporarily reverse signs of GWI pain in rats. In our proposed experiments, we will test the capacity other FDA-approved KVOs to relieve pain in our Gulf War pain model. We will further examine how combinations of KVOs, acting at distinct molecular binding sites, but in synergistic combinations, might substantially improve pain relief. Because these KVOs are FDA-approved drugs that are currently used in the treatment of human disease, it may be possible to rapidly, if not immediately, repurpose them for treatment of the chronic pain of GWI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910657
Entities
People
- Brian Cooper
Organizations
- United States Army
- University of Florida