Determination and Validation of Surrogate Biomarkers and Oxidation-Reduction Potential (ORP) in Lower Back Pain LBP Longitudinal Serum Samples

Specific Aims

Lower Back Pain (LBP) defined as back pain in the absence of a specific underlying condition that can be reliably identified is the leading cause of disability, caused by various spine related disorders, including intervertebral disc degeneration and disc herniation amongst others. Currently, patient response to treatment is unpredictable with a significant rate of recurrence, and, while surgical treatments may provide anatomical correction and pain relief, they are invasive and costly. Since the natural history of LBP is progressive, the temporal nature of studies (i.e. longitudinal cohorts) is categorized by duration of symptomology/disease. Increasingly, studies deriving from Lower Back Pain (LBP) cohorts is suggesting that the presence of inflammatory mediators can be measured systemically in the blood. Clinically, LBP consists of multiple diseases, influenced by multifactorial processes, governed by genetics, lifestyle, and comorbidities (diabetes and obesity). Pinpointing the cause of LBP presents the biggest challenge to physicians in this field. Ultimately, diagnostic biomarkers of LBP and spinal degeneration have the potential to shepherd an era of individualized spine medicine for personalized therapeutics in the treatment of LBP. A detailed meta analyses of the literature is suggesting that the following biomarkers may serve as novel tools for directing patient care 1 2.

Specific Aim 1: Validate hsCRP, TNF-a, sTNFR1, and IL-6 as Acute and Subacute biomarkers

Specific Aim 2: Evaluate that IL-6, TNF-a, IL-8, IL-1f3 and RANTES are candidates that provide a measure of Chronic LBP

Specific Aim 3: Correlate Disc Herniation with Elevated levels of IL-2, IL-6, IL-8, TNF-a, IL-17, IL-18 IL-21,and COX-2

Specific Aim 4: Measure and correlate values of MCP-1 and MIG) and factors that participate in mechanisms of angiogenesis (HGF and VEGF), inflammation (IL-1f3, IL-1ra, IL-9, IL-12, and TRAIL), and nociception (SCF and IFN-a2)

Specific Aim 5: Measure the Oxidation Reduction Potential (ORP) of serum and blood samples using a disposable electrochemical sensor. Though the pathway from disc degeneration to its associated pain is not yet established, there is evidence suggesting that the degenerate disc is more acidic due to increased levels of glycolysis and lactate secretion and recent studies have eluded to a possible connection between low pH levels within the disc and lower back pain

The findings from this study would lead to the development and testing of pharmaceutical, behavioral, physical or surgical interventions by biomarker identified lumbar spine phenotypes. In Aim 1, we will demonstrate the degree to which biochemical biomarkers predict the incidence or progression of cLBP.

We will determine longitudinal relationships between pain and quantitative sensory biomarkers. Biomarkers that allow for earlier diagnosis of disc degeneration and are needed to provide evidenced- based metrics for preventative interventions and could potentially be used to monitor disease progression or responses to therapeutic interventions, both surgical and nonsurgical.

By putting multiple targets together, biomarker profiling is a powerful technology that will greatly accelerate progress toward novel diagnostic and predictive tools to track early disease and tailor treatments to specific patients.

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