DESCRIPTION (APPLICANT'S ABSTRACT): Neuropathic pain can result from nerve injury or numerous disease processes, and occur without axonal injury. Symptoms are typically difficult to manage clinically, and include nerve trunk pain, perceived locally at the nerve, and dysesthetic pain, perceived in the nerve's distal distribution. Painful symptoms can be spontaneous, and can also be reproduced by many cases of dysesthetic pain by movement of the affected nerve, or the tissue surrounding it. Observations of mechanically-evoked dysesthetic pain imply that axons have or acquire a transductive mechanism at the site of pathology. The proposed experiments address the hypothesis that dysesthetic pain results from sensitivity changes of nociceptor axons due to inflammation of the nerve that carries its axon. Single-unit recording will be made from dorsal root C-fibers with a nociceptive receptive field in the hind limb. The sciatic nerve will be identified in mid thigh, remote from the receptive field. Endogenous algesic chemicals, inflammatory mediators, and pro-inflammatory agents will be applied to the nerve. The properties of the neuron, including the mechanical sensitivity of the axon, will be tested before and at various times following application. In other experiments, a chronic neuritis will be induced and the neurons similarly tested. These experiments test the hypothesis that inflammation of a nerve induces changes in neuronal function. Additional, the answers to the posed questions will address part of a novel hypothesis of movement-induced pain generation. Descriptions of neuropathic pain are similar to those characteristics of some forms of chronic musculoskeletal pain, such as myofascial pain syndrome, fibromyalgia, and back pain. Research into these disorders has focused on various somatic tissues as a pain source, but the etiologies remain elusive and thus the disorder are different to treat. It is possible that these disorders are misdiagnosed neuropathy. Existing data suggest that focal neuropathies are the root pathology in some chronic musculoskeletal diseases, especially back pain, that typically are symptomatically worsened by movement. The information provided by the proposed studies will help form a foundation for development of an animal model of chronic, movement-induced musculoskeletal pain.