Acute-to-Chronic Transition in Ergonomic Muscle Pain: Nociceptor Mechanisms

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DESCRIPTION (provided by applicant): Musculoskeletal pain is the most frequent and expensive condition for worker compensation and disability. Previous investigations into the pathogenesis of work- related musculoskeletal pain have tended to focus on the possibility of pathology in muscle cells; however, it is clear that chronic ergonomic muscle pain can occur without any signs of cellular injury in the muscle. During the current funding period we have provided extensive evidence, in two animal models of ergonomic muscle pain (vibration and eccentric exercise) that the muscle nociceptor is a primary locus of pathophysiological changes that produce chronic muscle pain. Furthermore, these models exhibit a neuroplastic shift from acute hyperalgesia to chronic hyperalgesic priming that enables us to study the cellular mechanisms of the transition from acute to chronic muscle pain. Based on those findings, this proposal outlines a project that will employ two innovative approaches to advance our understanding of the underlying cellular mechanisms of chronic muscle pain. First, we will pursue our preliminary observations which suggest a discrete subpopulation of nociceptors plays a critical role in chronic ergonomic muscle pain, and that distinctive features of this subpopulation (sensitivity to GDNF and versican-dependent binding of IB4) are not just convenient markers to distinguish them from other subpopulations, but in fact, play a crucial role in their unique contribution to chronic muscle pain. Second, in view of the prominent clinical role stress plays in the pathophysiology of chronic muscle pain syndromes, we will investigate the nociceptor as a primary site at which activation of neuroendocrine stress axes contributes to chronic pain. The multi-disciplinary expertise of the PI's laboratory enables this proposal to outline a research plan based on the concerted use of behavioral, pharmacological, anatomical, and in vivo electrophysiological and in vitro neurophysiological methods.