Low back pain (LBP) is an extremely common musculoskeletal disorder that affects an estimated 80% of people at some time in their lives and represents the most common cause of disability
. Chronic LBP (CLBP) is the most frequent cause of activity limitation in adults under the age of 45
. Common causes of LBP include disc degeneration, lumbar disc herniation (LDH), lumbar spinal stenosis, lumbar instability syndrome, and waist soft tissue lesions
[3–5]. Clinically, only a small proportion (~20%) of LBP cases can be attributed with reasonable certainty to a pathologic or anatomical entity, because most of the signs and symptoms are not specific and are difficult to distinguish among diseases that exhibit LBP
. In addition, there exist a significant number of cases of CLBP of unknown origin. Therefore, an accurate diagnosis of the cause of LBP represents a great challenge to orthopedists.
Disc degeneration can cause persistent pain and is believed to be a major cause of CLBP
. Clinical disease resulting from this pathological process is known as discogenic low back pain (DLBP). DLBP and LDH are the two most common causes of CLBP, accounting for ~40% and ~30% of all cases of CLBP, respectively
[2, 7–12]. In contrast to LDH, DLBP is not accompanied by radicular symptoms or radiological evidence of excessive activity of nerves or segments
. Given that DLBP is clinically featured with many subjective symptoms, numerous risk factors, but has few objective positive markers and unclear pathogenesis, its diagnosis is often elusive
. Discography is currently the main diagnostic modality for DLBP; however, its reliability is controversial because discographic results rely heavily on the reproduction of the patient’s pain and the operator’s judgment and is therefore largely influenced by subjective factors. In addition, discography can cause many complications due to its invasive nature
. Thus, there is an intense debate over discography as a diagnostic tool to distinguish DLBP from other forms of CLBP and a more accurate, reliable and non-invasive diagnostic method is required.
DLBP is caused by a variety of pathologic processes, including degeneration, endplate damage and inflammation, which stimulate the intradiscal nociceptors while the disc periphery remains intact
. Normally there is a high density of blood vessels and nerves in the outer 1/3 of the annulus fibrosus, but not inside the disc. Degenerated intervertebral disc induces crack formation in the endplate and the outer 1/3 of the annulus fibrosus due to biomechanical reasons. As disc degeneration progresses, nascent vascular nerve endings grow inward along the fissure to form inflammatory granulation tissue that leads to the distribution of vessels and nerves inside the disc, even within the nucleus pulposus
. During this process, biochemical, metabolic, inflammatory and immuno-reactive products from damaged cells can enter the bloodstream and alter the blood protein spectrum
. Since certain serum proteins can serve as diagnostic markers for the disease that causes their release from cells
, serum proteomic profiling of DLBP will provide a means to identify diagnostic biomarkers for this clinical entity. Identification of objective biomarkers in serum that can aid in differential diagnosis would be of great clinical benefit.
Most serum proteins, including disease biomarkers, are often present in small amounts and are difficult to detect using conventional methods
. Capture of low-abundance proteins is critical for facilitating marker discovery. Bead-based fractionation can greatly enrich low-abundance proteins and selectively separate certain peptides according to different chemical chromatographic surfaces on the outer layer of magnetic beads. The combination of bead-based fractionation with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been widely used for disease detection and biomarker identification using human body fluids (e.g., blood and urine), and carries advantages such as minimal invasiveness, high efficiency, low cost, and easy manipulation
. The more sophisticated techniques, such as Fourier transform ion cyclotron resonance tandem mass spectrometry (MS/MS) and linear trap quadrupole orbitrap MS, allow the direct identification of peptide sequences. Currently, there have been no reports of the use of these techniques for disease detection and biomarker identification in patients with DLBP.
In the current study, we conducted a MALDI-TOF-MS analysis of serum samples from patients with DLBP, chronic LDH, or CLBP of unknown origin, and normal controls, with an aim to establish diagnostic models for classification of these different entities and identify serum biomarkers for differentiation of DLBP from other forms of LBP.