Insights into the pleiotropic relationships between chronic back pain and inflammation-related musculoskeletal conditions: rheumatoid arthritis and osteoporotic abnormalities

Abstract

Supplemental Digital Content is Available in the Text.The genetic relationship between chronic back pain and its risk factors, including rheumatoid arthritis and bone mineral density irregularities, may be explained by horizontal pleiotropy.

Genetic impact of blood C-reactive protein levels on chronic spinal & widespread pain

“…The Mendelian randomisation results suggest a putative bidirectional causal relationship between chronic neck/ shoulder pain & higher CRP, as well as a causal role of CRP in chronic back & widespread pain. These findings are consistent with a recent Mendelian randomisation study reporting a causal effect of CRP on back pain [11], while also extending upon that work by finding a causal effect on neck/shoulder & widespread pain. Together these studies…”

“…Mendelian randomisation (MR) analyses suggested a bidirectional causal association between CRP & chronic neck/shoulder pain, and potential causal effects of CRP on chronic back & widespread pain. These findings replicate and expand upon the study by Kasher et al [11], which reported a genetic correlation and putative causal effect between CRP & chronic back pain In the current study, GWAS analyses of chronic pain were limited to people of European ancestry, so it is unclear whether the findings can be extrapolated to non-European populations. The LCV analyses provided estimates of the likelihood of observed genetic correlations being attributable to a genetic causal effect of one trait (pain) upon another (CRP) or vice versa [18].…”

“…This study has demonstrated a genetic contribution of systemic inflammation in chronic spinal & widespread pain. It also extends upon prior studies reporting genetic correlations between CRP and back pain [11], osteoarthritis [21] & rheumatoid arthritis [21], by finding a genetic basis to higher CRP across a wider range of chronic pain phenotypes. Moreover, we have provided corroborating evidence for clinical studies showing higher CRP levels and other inflammatory markers in chronic back, neck & widespread pain [2][3][4].…”

“…Only recently have GWAS data been used to explore the relationship between systemic inflammation & pain conditions. Kasher et al [11] reported genetic correlations between higher circulating CRP and an increased risk of chronic back pain. Using Mendelian randomisation analyses, they also suggested that CRP had a causal influence on back pain.…”

Big data, big consortia, and pain: UK Biobank, PAINSTORM, and DOLORisk

“…As the genetic variants inherited by an individual are randomly assigned at conception and not subject to modification, it allows genetic markers to be used as a “proxy” for the exposure of interest, thus eliminating the risk of confounding or reverse causation. These studies have been able to establish a causal effect of C-reactive protein, 65 insomnia 103 and iron blood serum status 117 with back pain, and diabetes with frozen shoulder. 53 Furthermore, a bidirectional relationship was found to exist between insomnia and CP 21 and between prescription opioid use and depression and anxiety disorders, 100 whereas multisite CP was found to be a causative for major depressive disorder 63 and far sightedness.…”