Low back pain is a globally debilitating health condition, and chronic low back pain is a common health issue that has substantial financial and social costs. However, the mechanism of pain induction and perception in the context of low back pain remains unclear.
Low back pain is considered to involve multiple systems including muscles, nerves, the spine and intervertebral discs. Recently, several reports revealed that chemical stimuli and inflammatory mediators such as cytokines produce extracellular molecules such as high mobility group box 1 (HMGB1), which is activated by two receptor types: receptor of advanced glycation end-products (RAGE), and Toll-like receptor. Meanwhile, advanced glycation end-products (AGEs) such as pentosidine are modifications of proteins or lipids that become nonenzymatically glycated and oxidized [1]. AGEs accumulate in the elderly as well as in patients with diabetes or renal failure [2–5]. As such, AGEs can act as an aging marker.
RAGE belongs to the immunoglobulin superfamily of receptors [6], and localizes in tissues involved in ascending sensory pathways (e.g., skin, peripheral nerve, dorsal root ganglion, and spinal cord) as well as in endothelial cells, smooth muscle cells, monocytes, and macrophages [1].
RAGE plays an important pathological role in neuropathic pain and is expressed in response to injury, inflammation and diseases that affect sensory nerves [7].
Some reports show that AGE crosslinking can degrade the mechanical and biological functions of bone [8, 9]. Recent studies suggest that AGEs accumulation is independently related to risk of bone fractures, diminished ability to walk and perform activities of daily living (ADL), declines in muscle properties and increased physical frailty. AGEs can thus be a potential risk factor and biomarker for decreased motor function [10–12], and represent a potential risk factor for frailty in the elderly [13]. AGEs may also promote bone degeneration or fracture, muscle stiffness, reduced muscle function, and neuropathy that are all associated with orthopedic pain including low back pain. Indeed, high serum levels of AGEs are reported to be associated with degenerative lumbar scoliosis [14].
The AGE reader has been developed to quantify skin autofluorescence (SAF), and has been proposed as a simple alternative to invasive measurement of AGE accumulation. Several reports showed that the amounts of serum pentosidine and SAF are significantly increased in patients undergoing hemodialysis [15] and those with type 2 diabetes (T2DM) [16].
A study involving patients with diabetes showed that knee extension strength was negatively correlated with SAF, but not with skeletal muscle mass index [16]. Meanwhile, SAF was reported to be associated with low skeletal muscle mass index among middle-aged Japanese [17]. Together these findings suggest that the behavior of SAF in orthopedic patients could have diagnostic value.
We hypothesized that AGE accumulation is associated with chronic low back pain. The aim of the present study was to determine whether AGE levels revealed by SAF can serve as a biomarker for chronic low back pain.