Many veterans of the 1991 Gulf War returned from service with a wide variety of sensory, motor, and cognitive symptoms known as Gulf War Illness. A portion of these soldiers experienced a chronic and widespread joint and muscle pain that was unrelated to any physical injury incurred during deployment. Although the precise events leading to the chronic pain in Gulf War Illness are unknown, we have determined that certain membrane proteins expressed in vascular system neurons are misregulated following chronic exposure to specific insecticides and a nerve gas prophylactic that was widely used in the Gulf theatre. In our studies, we will use a rat model to determine the persistence of behavioral, cellular, and molecular consequences of chronic exposure to pyridostigmine bromide, permethrin, and chlorpyrifos. In molecular studies, we will focus on altered physiology of proteins expressed in pain system neurons that innervate vascular tissue. These neurons appear to be a selective focus of molecular defects.

By identifying specific proteins in pain system neurons whose functions are disturbed by the synergistic actions of neurotoxicants, we will have identified systems and molecular targets for drug development and genetic engineering. Moreover, dependent upon our detailed findings, we hope to identify molecules modulated by Food and Drug Administration-approved agents that will ultimately reverse the sensory, cognitive, and motor syndromes of Gulf War Illness that may share a common molecular defect.