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 the total number of painful sites were calculated. Targeted metabolomic profiling on fasting plasma samples was performed using the Biocrates AbsoluteIDQ p180 kit. Plasma cytokine concentrations including tumor necrosis factor-α, interleukin-6, interleukin-1β, and macrophage migration inhibitory factor were assessed by enzyme-linked immunosorbent assay. Data on blood cholesterol profiles were 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 83 who had ≥7 painful sites and 122 who had ≤1 painful site. Women and younger people were more likely to have MSMP (P ≤ 0.02). Multisite musculoskeletal pain 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, 2 lysophosphatidylcholines, 1 with 26 carbons with no double bond and 1 with 28 carbons with 1 double bond, were significantly and positively associated with MSMP after adjusting for multiple testing with the Bonferroni method (P ≤ 0.0001) and could be considered as novel metabolic markers for MSMP.