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.