Widespread joint and muscle pain is a frequent and debilitating component of Gulf War Illness. In our proposed studies, we will examine mechanisms that could be responsible for the spontaneous and widespread pain that affects so many of these veterans. The precise events leading to chronic pain in Gulf War veterans are unknown. Synergistic actions of neurotoxicants pyridostigmine bromide and permethrin are strong candidates as they have known acute interactions with proteins that are expressed in the pain system. The chronic influences of these neurotoxicants on pain system proteins are not known. In a rat model, we will determine the dose combinations and time course of behavioral and neurophysiological consequences of neurotoxicants pyridostigmine bromide, permethrin, and chlorpyrifos. In electrophysiological studies, we will focus on altered physiology of proteins expressed in pain system neurons in muscle and vascular tissue.
By identifying specific proteins in pain system neurons that are dysregulated by synergistic actions of neurotoxicants, we will have identified systems and molecular targets for drug development and genetic engineering. Moreover, we will be able to test the capacity of known agents to reverse physiological and behavioral effects. In some cases, agents acting on the candidate proteins are under development or in clinical trials. Treatment with these compounds might be possible within a couple of years.
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