Role of Vitamin C in Low back Pain and Intervertebral Disc Degeneration

PROJECT SUMMARY / ABSTRACT Persistent back pain is a leading cause of disability worldwide and one of the most common reasons pa- tients are prescribed opioids, despite their poor ability to improve function. Chronic back pain threatens our economic health due to high rates of health care utilization and disability and our quality of life due to pain-related suffering, pain-associated opioid misuse, depression, and anxiety. The primary driver in 40% of all low back pain (LBP) cases is estimated to be pain from intervertebral disc (IVD) degeneration. Ex- isting symptomatic (e.g., analgesics) or invasive (e.g., spinal injections, surgery) treatments have limited efficacy and are associated with risk for opioid misuse or surgical complications, respectively. There is an urgent need for safe and effective treatments for chronic LBP that can be rapidly translated to the clinic. Disc degeneration is associated with decreased production of extracellular matrix (ECM) components including collagen and proteoglycans. DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified in response to local, environmental, or pharmacological factors. We have previously shown that a non-invasive treatment (running exercise) attenuates behavioral signs of chronic LBP, increases IVD collagen production, and decreases IVD global methylation. Ascorbic acid (vitamin C) is essential for collagen production and is involved in the regulation of DNA methylation. Ascorbic acid is safe for daily consumption and its deficiency is correlated with musculoskeletal pain in elderly. Although ascorbic acid exhibits analgesic properties in some conditions and is essential for colla- gen synthesis and musculoskeletal health, its therapeutic potential for LBP has not been studied. The overall objective for this application is to determine the therapeutic outcomes of ascorbic acid treat- ment in discogenic LBP and IVD degeneration using a pre-clinical model of progressive IVD degenera- tion associated with LBP. Our central hypothesis is that ascorbic acid reprograms expression of ECM genes by decreasing DNA methylation in degenerated IVDs, thereby attenuating discogenic LBP. In Spe- cific Aim 1, we will examine the therapeutic efficacy of long-term ascorbic acid supplementation (4 months) on the prevention and treatment of LBP and disc degeneration using a mouse model. In Specific Aim 2, we will determine the effects of vitamin C on DNA methylation and mRNA expression of ECM genes, with emphasis on collagens and proteoglycans, and will correlate these data to disc pathology and behavioral signs of LBP. The expected outcomes are that we will observe therapeutic effects of ascorbic acid on LBP and IVD degeneration (Aim 1) associated with reprogramming of IVD DNA methyl- ation (Aim 2). These results will provide critical proof-of-concept data for using noninvasive, safe, dietary vitamin C supplementation as a treatment for discogenic LBP.