Exploring the Role of Extracellular Matrix Organization in the Progression of Chronic Low Back Pain

PURPOSE: Chronic low back pain (CLBP) is the leading disability in the world, and novel approaches for more effective treatment of CLBP are warranted. Individual genetic differences in pain genes may explain the differences in pain perception. It has been recently found that the extracellular matrix organization is the most regulated pathway in inflammatory and neuropathic pain assays in mice. This project explores the role of ECM variability in the incidence and trajectory of CLBP. This project has two aims: 1) to identify low-risk and high-risk genotypes for ECM genes between two groups of participants, CLBP and chronic widespread pain (CWP), through a retrospective case-control study; and 2) to assess if the identified genetic risk factors are associated with longitudinal outcomes in pain intensity and quality of life through a cohort study. METHODS: Using genetic data from the PRECISION Pain Research Registry, single SNP, SNP-set, and epistasis analyses for ECM-related genes were run using PLINK and CASSI. Necessary adjustments for the covariates age, gender, and genetic ancestry were done. RESULTS: Epistasis relevant to chronicity of low back pain were identified in TNFBxPRTN3, VWFxMMP9, TNF xMMP13, and PRTN3xLILRA5 for African Americans. In non-Hispanic Whites, epistasis between VWFxMMP2, SPARCxMMP2, and VWFxELANE were significantly related to chronicity of low back pain. CONCLUSION: This study suggests that race/ethnicity specific interactions between variants in ECM-related genes may play an important role in progression of chronic low back pain and perhaps useful in formulating precision approaches to CLBP therapeutics.