Metabolomic analysis coupled with extreme phenotype sampling identified that lysophosphatidylcholines are associated with multisite musculoskeletal pain.

Musculoskeletal pain often occurs simultaneously at multiple anatomical sites. The aim of the study was to identify metabolic biomarkers for multisite musculoskeletal pain (MSMP) by metabolomics with an extreme phenotype sampling strategy. The study participants (n=610) were derived from the Newfoundland Osteoarthritis Study. Musculoskeletal pain was assessed using a self-reported pain questionnaire where painful sites were circled on a manikin by participants and total number of painful sites were calculated. Targeted metabolomic profiling on fasting plasma samples was performed using Biocrates AbsoluteIDQ® p180 kit. Plasma cytokine concentrations including tumor necrosis factor-α, interleukin-6, interleuin-1β, and macrophage migration inhibitory factor were assessed by enzyme-linked immunosorbent assay. Data on blood cholesterol profiles was retrieved from participants' medical records. Demographic, anthropological, and clinical information was self-reported. The number of reported painful sites ranged between 0 and 21. Two hundred and five participants were included in the analysis comprising of 83 that had ≥7 painful sites and 122 that had ≤1 painful site. Females and younger people were more likely to have MSMP (p≤0.02). MSMP was associated with a higher risk of having incontinence, worse functional status and longer period of pain, and higher levels of low-density lipoprotein and non-high-density lipoprotein cholesterol (all p≤0.03). Among the 186 metabolites measured, two lysophosphatidylcholines, one with 26 carbons with no double bond and one with 28 carbons with one double bond were significantly and positively associated with MSMP after adjusting for multiple testing with Bonferroni method (p≤0.0001) and could be considered as novel metabolic markers for MSMP.