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The SPARC-null mouse model of low back pain: Mechanism, Treatment, and Translation to Humans

Year: 2013
Type: dissertation
Abstract: Persistent low back pain (LBP) is the most common form of chronic illness in Canadians age 60 and under, affecting 15% of the population. In addition to being a major health problem, it also has serious economic consequences. Current diagnostic and therapeutic approaches to chronic back pain are limited by our narrow understanding of the underlying biological mechanisms. As a consequence, treatment is not always effective and individuals may suffer for years without relief. LBP is often associated with signs of degeneration in the intervertebral discs. LBP encompasses a wide spectrum of pain disorders including axial pain in the back region and radiating pain down one or both legs. This thesis investigates the mechanisms and treatment of axial and radiating pain associated with disc degeneration (DD) in a transgenic mouse model and in human subjects. SPARC-null mice show anatomical signs of disc degeneration and behavioral signs of pain and are thus a valid model of LBP due to DD.Our results show that loss of lumbar disc height correlates with radiating pain in mice. In addition, we show that axial pain and radiating pain have different pharmacological profiles, suggesting the involvement of different mechanisms. Furthermore, we explore the use of opioid-adrenergic combination therapy to improve therapeutic outcome in our model. Finally, we propose an epigenetic mechanism governing SPARC expression, disc degeneration, and back pain in aging wild-type mice and in human subjects with LBP.The results shown in this thesis will serve to increase our understanding of the mechanisms of pain due to DD. This mechanism-based approach is key in improving therapeutic options for the millions of patients suffering from chronic low back pain.
DOI: 10.82308/53581
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W6996582247
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