Chronic Low Back Pain (LBP)

Abstract:
Chronic low back pain (LBP) affects over 10% of the adult population and seriously decreases the quality of life. The aging intervertebral disk (IVD) is prone to degeneration, which is associated with an increased risk of LBP. Physical activity influences IVD physiology. Animal studies show that cyclic loading increases proteoglycan synthesis in the disk suggesting a role for running exercise in disk repair. Additionally, an active lifestyle has been shown to either contribute to the onset of chronic pain onset or to be protective against chronic pain depending on the circumstances.
Total 2- to 3-month-old male SPARC-null and C57B wild-type mice were used in this study.
After recording baseline behavioral measurements, animals had free access to either a circular treadmill (exercise group) or a fixed nonrotating treadmill (control group) in their home cages.
Axial LBP was assessed using the tail suspension test and radiating LBP was assessed using the acetone test for cold hypersensitivity in the hind paw.
SPARC-null mice exhibit signs of both axial and radiating LBP in these assays that are sensitive to pharmacological manipulation.
Additional assays included tests for mechanical sensory thresholds and motor capacity. Tests were performed at 2 weeks and monthly thereafter. After 2 months with access to running wheels, SPARC-null mice show significantly reduced cold sensitivity in the hind paw compared to baseline (p < 0.05) and control group (p < 0.01) with no accompanying change in mechanical sensitivity, indicating a reduction of radiating pain.
No effect on axial pain was detected in the tail suspension test, suggesting an effect specific to radiating pain. Our results shed light on behavioral correlates of physical exercise on pain and motor function in an animal model. These results could have potential translational value for the pain patient.
Introduction:
Low back pain (LBP) is the leading cause of disability compared to any condition globally and has been documented as a source of chronic disability among both men and women within the working-age bracket1. Nasution et al. have cited that low back pain (LBP) is a leading cause of disability globally2. In 2013, the World Health Organization estimated that the prevalence of LBP could be between 60 and 70 percent among developed countries. These estimates indicate that over 70 percent of people in industrialized nations will experience chronic pain at some point in their lives. LPB is strongly associated with the degeneration of the intravertebral discs (IVDs) resulting from metabolic, structural, and biochemical changes in the discs. While metabolic changes involve processes such as reduced synthesis of the matrix, an example of structural changes includes annular tears and biochemical changes often accompanied by the loss of are and proteoglycan content. Chronic low back pain is classified as LBP that lasts more than 3 months and results from multiple pathologies2. Although these changes are often presented by patients with LBP, IVD degeneration may also occur among asymptomatic individuals, making a clinical diagnosis of LBP based on IVD degeneration irrelevant1. A deeper understanding of the mechanisms of IVD and LBP relation is required and taking both animals and humans as subjects will provide empirical data that can be analyzed to derive valuable conclusions. While much has been studied about the association between IVD and LBP, existing literature has not exhaustively shown evidence of any positive rewards of physical activities or exercises such as running with IVDs3. This observation may be due to humans’ slow IVD metabolism, making them slow to express anabolic responses to exercise within their lifespans. However, Belavy et al3. have shown that chronic running is often associated with the better composition of IVD in terms of proteoglycan content and hydration and IVD hypertrophy among men and women. Exercise serves to protect the aging IVD, which is often prone to degeneration. Danco et al. have shown that IVD is often associated with an increased risk of LBP but according to their study results, physical exercise tends to improve IVD physiology and ultimate quality of life (QoL) or increase risks of LBP4. However, accumulating evidence from other studies such as Mitchell et al confirms the long-term benefits in improving IVD physiology5. Using animal studies, this research attempts to fill the gap in associating physical activities with health IVD in humans. Current knowledge about muscles tends, and bones show that they only respond to mechanical forces anabolically. However, according to Owen et al, it is not yet clear that IVDs can too benefit from physical activity6. Experiments with mice have shown that cyclic loading is positively associated with increased synthesis of proteoglycan in the disk4. These observations are also in part similar to Danco et al4 conclusions that active lifestyle among humans is often associated with reduced risks a reduction in the risks been shown to either play a protective role against chronic low back pain (CLBP) or a contributor to the early onset of chronic pain. The recommendations of having regular and moderate exercise from physicians emerge from scientific data that has often supported the result the world. Based on results obtained in this study as well as accumulated evidence from past animal research studies, we hypothesize the potential benefits of exercise in pain response and the physiology of intervertebral disks, which could play a critical role in preventing disk degeneration and lower back pain in humans.
Methods:
In the present work, male 21 SPARC-null and 23 C57B wild-type (WT) mice with ages ranging between 2 and 3 months were studied. The WT mice are commonly used for transgenic or genetic studies and portray the highest levels of voluntary when it comes to wheel-running7. Secreted protein acidic and rich in cysteine (SPARC)-null mice were also the right candidate for this study to elucidate different molecular mechanisms that are directly related to exercise. Besides, SPARC-null mice have shown both behavioral signs of pain and anatomical signs of IVD degeneration, which makes them the appropriate model for this study. Although many studies have shown the benefits of exercise, such mechanisms remain poorly understood. At the same time, skeletal muscles in both humans and animal studies are examples of secrete organs that secrete different forms of myokines such as SPARC7. The mice were fed with a protein diet and allowed access to both water and food ad libitum during the period of the study that lasted 12 months, except for shorter fasting periods that they were only given water. The WT mice were obtained from MOUSE Laboratories Inc. while the SPARC-null mice were generated by crossbreeding SPARC with C57BL/6 up to 10th generation. All experiments in this study were conducted following the University Bioethics Committee and Animal Protection Consortium. During the entire period of the study, the animals were provided with free access to either a stationary or nonrotating wheel (control subjects) or a rotating treadmill for the exercise subjects.
We then assessed the axial LBP using the tail suspension test and radiating LBP using the acetone test. In between the 12 months that were set aside for the study, the exercise group was required to be conditioned although in most cases they completed the running voluntarily after c...