Michael Smith, PhD - US grants

DESCRIPTION (provided by applicant): How aging and noise exposure interact to produce hearing loss is an important issue for understanding its etiology. The relationship between age-related hearing loss (AHL) and noise-induced hearing loss (NIHL) is not always additive. Studies using mammalian models suggest that sensitivity to acoustic trauma may be greatest during the extremes of ontogeny - that is, in developing animals and in senescent animals. Zebrafish (Danio redo) have become a popular vertebrate model for examining embryogenesis and genetic defects because there is considerable synteny between zebrafish and human genes. Thus zebrafish mutations that affect ear development, or interact with age to affect hearing, may shed light on similar pathologies in humans. Although age-related shifts in hearing has been examined in developing fishes, the effects of degeneration due to senescence have not been examined in zebrafish or any other teleost. In order to fully understand the effects of inner ear genetic mutations and NIHL in the zebrafish model, baseline data of age-related shifts in hearing capabilities in wild type zebrafish are needed. The purposes of the proposed research will be to 1) examine shifts in hearing capabilities with age and 2) determine how aging (AHL) and noise exposure (NIHL) interact to cause hearing loss in zebrafish. To fulfill these goals, zebrafish will be exposed to specific sound exposures at various ages, and then pathology of the inner ear (via SEM) and hearing thresholds (via auditory brainstem response) will be examined.

The Graduate School of Biomedical Sciences (GSBS) is collaborating with the Texas College of Osteopathic Medicine (TCOM) at UNTHSC, and the Arizona College of Osteopathic Medicine (AZCOM) to propose a Developmental Center for Research on Osteopathic Manipulative Medicine (DCR-OMM). OMM is a body-based therapy as defined by the NCCAM definitions of complementary and alternative medicine (CAM). The varied principles and practices of OMM are unique among other body-based therapies primarily because they are applied by fully licensed physicians and therefore can be applied to alleviate both musculoskeletal and visceral disease processes and readily integrated with conventional health care. Four key elements of osteopathic principles and practices will be investigated in this DCR-OMM: Study #1) Effects of direct biomechanical strain on the fascial tissues of the musculoskeletal system;Study #2) Effects of OMM (lymphatic pump) on the lymphatic duct lymph flow and the resultant potential beneficial effects on edema and immune function subsequent to an improvement in lymphatic circulation;Study #3) Effects of OMM on sympathetic neural activity either by affecting the sympathetic nervous system directly or by affecting the sympathetic nervous system indirectly by reduction of somatic dysfunction induced pain;and Study #4) Combined synergistic clinical outcome effects that result from applying OMM in patients post -CABG who have a complex combination of fascial restrictions, pathologic fluid shifts, somatic pain and hypersympathotonia. In 2001, the leading national osteopathic professional organizations endorsed and funded these investigators to establish a national Osteopathic Research Center (ORC) housed within the Physical Medicine Institute at the University of North Texas Health Science Center. The OMM research mission of the ORC is perfectly aligned with the goals of the U-19 DCR-OMM and the research priorities of NCCAM. We are all dedicated to the success of this DCR-OMM with the goal of developing into a P-01 Center of Excellence for Research on OMM to enable quality investigation and publication of the mechanisms of OMM.

Osteopathic manipulative medicine (OMM) is a body-based therapeutic approach that has been proven to be efficacious for many clinical conditions. In particular, OMM is commonly used for musculoskeletal conditions and is known to reduce pain. A theoretical foundation of OMM has long been that somato-visceral interactions also can be affected by specific OMM techniques; however, very limited data exist to support or refute this tenet. This proposal will be the first systematic series of studies that address this fundamental hypothesis. OMM techniques include 1) those directed at reducing sympathetic neural activity (SNA), or sympatholytic OMM, and 2) techniques directed at relieving pain and somatic dysfunction at the site of musculoskeletal injury. An initial study, tested the effect of sympatholytic OMM and found that basal sympathetic nerve activity (SNA) can be reduced (20-50%) in healthy subjects free of any pain syndrome. The proposed studies represent an extension of these initial findings. This project #3 will contribute to the overall goal of the proposed developmental center on the mechanisms of OMM by testing the efficacy of the two OMM modalities noted above. Pain accompanies most musculoskeletal injuries and an important part of a pain-mediated stress response is an activation of the sympathetic nervous system; thus, it follows that if OMM can reduce pain in certain conditions, it may also reduce SNA. In Study 1, intermittent cold pressor stimulus will be used to produce an experimental state of sustained elevation of SNA. We will use this condition to determine whether sympatholytic OMM can decrease a sustained elevation of SNA, and whether sustained pain-induced elevations in SNA persist when the stimulus is removed. Although hypothesized, it is not known whether OMM treatment of back pain and somatic dysfunction, can reduce SNA associated with either the pain or the somatic dysfunction. Therefore, in Study 2, it will be determined whether either OMM treatment modality can affect SNA in patients with back pain and somatic dysfunction. In addition, it will be determined whether OMM treatment effects on SNA are direct, or related to pain or somatic dysfunction. Like each of the other Units, these studies will provide critical seminal evidence regarding long-hypothesized, but under-investigated mechanisms of osteopathic manipulative medicine.