? This resubmission of MRSDA application #KO1 AR050146-01 outlines a challenging program of training and research in the sensory, inflammatory, and neuromuscular effects of endogenous muscle damage in humans (i.e., exercise-induced muscle damage). Such damage causes pain, altered pain responses, inflammation, inhibited neuromuscular function, and the performance of self-cara behaviors over several days to several weeks. Emphasis within this application is placed on the understudied relationships among the sequelae relevant to the public health problems of musculoskeletal pain and disability. The candidate is a new Assistant Professor with interdisciplinary training in Exercise Science and Psychology, who recently completed a NIAMS postdoctoral fellowship in pain research. The past work of the candidate has focused on developing a protocol for inducing clinically relevant muscle pain and studying sex differences, with measures based on self-report. The training proposed in this MRSDA application will maintain continuity with the applicant's previous work on exerciseinduced muscle pain while training the candidate in new measurement techniques and mechanisms to address more mechanistic research questions regarding inflammatory pain and neuromuscular function. Developmental objectives of the application include training in: (a) physiology of inflammation and muscle damage; (b) mechanisms of inflammatory pain; and (c) mechanisms of neuromuscular function. Also training in the following measurement methodologies is proposed: (a) inflammatory markers (e.g., enzyme linked immunoassays and histochemical analyses); (b) altered pain responses (e.g., central sensitization and referred pain); and (c) neuromuscular function (e.g., proprioception and muscle activation). These developmental objectives will be achieved through participation in coursework, workshops, practica, laboratory visits, scheduled meetings, and directed readings. The studies proposed test the following primary specific aims: (a) hypothesized relationships among inflammation, muscle pain, and strength loss across four days after exercise; (b) a hypothesized relationship between muscle pain intensity and the development of altered pain responses and referred pain; and (c) models of the relationship between muscle pain and activation. These activities will be supervised by new collaborators as well as a previous collaborator, who will each make significant contributions to achieving the developmental objectives and research specific aims. Based on the applicants' current level of development and interdisciplinary training needs, this application for a MRSDA mechanism is appropriate. ? ?
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