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Peripheral influences in the generation and maintenance of skeletal pain

Posted on:2006-08-24Degree:Ph.DType:Dissertation
University:University of MinnesotaCandidate:Mach, David ByronFull Text:PDF
GTID:1454390008456966Subject:Biology
Abstract/Summary:
Bone, a complex and dynamic connective tissue, has three primary functions which our body depends upon daily; provide mechanical support to our musculature, protect internal organs from physical trauma and act as a reservoir of major inorganic ions to help maintain our body's physiological balance. Diseases or disorders such as osteoporosis, osetopetrosis, Pagets, osteomylitis, craniosynostosis and bone cancer can affect the skeletal system and alter the body's physiological balance which can cause bone pain. Although bone pain reduces the patients' quality of life, little is known about the mechanisms that generate and maintain this pain.; To define the origin of skeletal pain we utilized current techniques in immunohistochemistry and micro-computed technology to analyze and delineate sensory and sympathetic innervation of a mouse femur. Understanding the neuronal subtypes which exist within bone allowed us to begin to understand the mechanisms that drive bone pain.; Bone pain is difficult to treat and it is one of the most common symptoms of bone cancer. In order to define the peripheral and central mechanisms of bone cancer pain, a murine model which clinically mirrors bone cancer was utilized. Animals injected with the osteolytic sarcoma cells were tested for behavioral, radiologic, histologic and immunohistochemical evidence of bone cancer pain over a designated time period. Animals also received a novel therapy Osteoprotegerin (OPG) and a gold standard therapy Alendronate, for the treatment of bone cancer. These results aided in our ability to identify the role of tumor cells, osteoclasts, and sensory neurons in the generation and maintenance of bone cancer pain.
Keywords/Search Tags:Pain, Bone cancer, Skeletal
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