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Background Context: Chronic low back pain (LBP) is a multifactorial disorder with complex underlying mechanisms, including associations with intervertebral disc (IVD) degeneration in some individuals. It has been demonstrated that epigenetic processes are involved in the pathology of IVD degeneration. Epigenetics refers to several mechanisms, including DNA methylation, that have the ability to change gene expression without inducing any change in the underlying DNA sequence. DNA methylation can alter the entire state of a tissue for an extended period of time and thus could potentially be harnessed for long-term pain relief. Lifestyle factors, such as physical activity, have a strong influence on epigenetic regulation. Exercise is a commonly prescribed treatment for chronic LBP, and sex-specific epigenetic adaptations in response to endurance exercise have been reported. However, whether exercise interventions that attenuate LBP are associated with epigenetic alterations in degenerating IVDs has not been evaluated.Purpose: We hypothesize that the therapeutic efficacy of physical activity is mediated, at least in part, at the epigenetic level. The purpose of this study was to use the SPARC-null mouse model of LBP associated with IVD degeneration to clarify (1) if IVD degeneration is associated with altered expression of epigenetic regulatory genes in the IVDs, (2) if epigenetic regulatory machinery is sensitive to therapeutic environmental intervention, and (3) if there are sex-specific differences in (1) and/or (2).Study Design: Eight-month-old male and female SPARC-null and age-matched control (WT) mice (n=108) were assigned to exercise (n=56) or sedentary (n=52) groups. Deletion of SPARC is associated with progressive IVD degeneration and behavioral signs of LBP. The exercise group received a circular plastic home cage running wheel on which they could run freely. The sedentary group received an identical wheel secured in place to prevent rotation. After 6 months, the results obtained in each group were compared.Methods: After 6 months of exercise, LBP-related behavioral indices were determined, and global DNA methylation (5-methylcytosine) and epigenetic regulatory gene mRNA expression in IVDs were assessed. This project was supported by the Canadian Institutes for Health Research. The authors have no conflicts of interest.Results: Lumbar IVDs from WT sedentary and SPARC-null sedentary mice had similar levels of global DNA methylation (%5-mC) and comparable mRNA expression of epigenetic regulatory genes (Dnmt1,3a,b, Mecp2, Mbd2a,b, Tet1-3) in both sexes. Exercise attenuated LBP-related behaviors, decreased global DNA methylation in both WT (p<.05) and SPARC-null mice (p<.01) and reduced mRNA expression of Mecp2 in SPARC-null mice (p<.05). Sex-specific effects of exercise on expression of mRNA were also observed.Conclusions: Exercise alleviates LBP in a mouse model. This may be mediated, in part, by changes in the epigenetic regulatory machinery in degenerating IVDs. Epigenetic alterations due to a lifestyle change could have a long-lasting therapeutic impact by changing tissue homeostasis in IVDs.Clinical Significance: This study confirmed the therapeutic benefits of exercise on LBP and suggests that exercise results in sex-specific alterations in epigenetic regulation in IVDs. Elucidating the effects of exercise on epigenetic regulation may enable the discovery of novel gene targets or new strategies to improve the treatment of chronic LBP. [ABSTRACT FROM AUTHOR]

Abstract: The National Institutes of Health (NIH) minimum dataset for chronic low back pain (CLBP) was developed in response to the challenge of standardizing measurements across studies. Although reference values are critical in research on CLBP to identify individuals and communities at risk of poor outcomes such as disability, no reference values have been published for the Quebec (Canada) context. This study was aimed to (1) provide reference values for the Canadian version of the NIH minimum dataset among individuals with CLBP in Quebec, both overall and stratified by gender, age, and pain impact stratification (PIS) subgroups, and (2) assess the internal consistency of the minimum data set domains (pain interference, physical function, emotional distress or depression, sleep disturbance, and PIS score). We included 2847 individuals living with CLBP who completed the baseline web survey of the Quebec Low Back Pain Study (age: 44.0 ± 11.2 years, 48.1% women) and were recruited through social media and healthcare settings. The mean score was 6.1 ± 1.8 for pain intensity. Pain interference, physical function, emotional distress or depression, sleep disturbance, and PIS scores were 12.9 ± 4.1, 14.4 ± 3.9, 9.8 ± 4.4, 13.0 ± 3.6, and 26.4 ± 6.6, respectively. Emotional distress or depression showed floor effects. Good-to-excellent internal consistency was found overall and by language, gender, and age subgroups for all domains (alpha: 0.81-0.93) and poor-to-excellent internal consistency for PIS subgroups (alpha: 0.59-0.91). This study presents reference values and recommendations for using the Canadian version of the NIH minimum dataset for CLBP that can be useful for researchers and clinicians., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)