Many Veterans of the 1991 Gulf War returned from service with a wide variety of autonomic, sensory, motor, and cognitive symptoms known as Gulf War Illness (GWI). A portion of these Soldiers experienced a chronic and widespread joint and muscle pain accompanied by autonomic symptoms that were unrelated to any physical injury incurred during deployment. Pesticides were widely used by Soldiers deployed to the Persian Gulf. We have determined that a 30-day exposure to Gulf War pesticides (permethrin, chlorpyrifos), repellants (DEET), and the nerve gas prophylactic pyridostigmine bromide produces a persistent joint and muscle pain that lasts for at least 15 weeks. Certain neural membrane proteins are directly affected by insecticides and may suffer long-term misregulation after being chronically exposed to these chemicals. In our studies, we will use a rat model of GWI to determine the persistence of autonomic, behavioral, cellular, and molecular consequences of chronic exposure to DEET, pyridostigmine bromide, permethrin, and chlorpyrifos. In molecular studies, we will focus on the physiology of proteins expressed in pain system neurons that innervate blood vessels. These neurons appear to be highly vulnerable to Gulf War pesticides. In treatment studies, we will examine the capacity of drugs that target the misregulated proteins, to reverse the established pain and autonomic signs of GWI in our rat model.

By identifying specific proteins in pain system neurons whose functions are disturbed by the actions of Gulf War chemicals, we will have identified systems and molecular targets for drug development and treatment. Moreover, by testing Food and Drug Administration-approved agents that target the misregulated proteins, we may be able to speed treatments to the clinic that will reverse the sensory and autonomic symptoms of GWI.