Lipidomic Profiling Identifies Serum Lipids Associated with Persistent Multisite Musculoskeletal Pain

Lipid mediators have been suggested to have a role in pain sensitivity and response; however, longitudinal data on lipid metabolites and persistent multisite musculoskeletal pain (MSMP) are lacking. This study was to identify lipid metabolic markers for persistent MSMP. Lipidomic profiling of 807 lipid species was performed on serum samples of 536 participants from a cohort study. MSMP was measured by a questionnaire and defined as painful sites ≥4. Persistent MSMP was defined as having MSMP at every visit. Logistic regression was used with adjustment for potential confounders. The Benjamini-Hochberg method was used to control for multiple testing. A total of 530 samples with 807 lipid metabolites passed quality control. Mean age at baseline was 61.54 ± 6.57 years and 50% were females. In total, 112 (21%) of the participants had persistent MSMP. Persistent MSMP was significantly associated with lower levels of monohexosylceramide (HexCer)(d18:1/22:0 and d18:1/24:0), acylcarnitine (AC)(26:0) and lysophosphatidylcholine (LPC)(18:1 [sn1], 18:2 [sn1], 18:2 [sn2], and 15-MHDA[sn1] [104_sn1]) after controlling for multiple testing. After adjustment for age, sex, body mass index, comorbidities, and physical activity, HexCer(d18:1/22:0 and d18:1/24:0) and LPC(15-MHDA [sn1] [104_sn1]) were significantly associated with persistent MSMP [Odds Ratio (OR) ranging from 0.25-0.36]. Two lipid classes-HexCer and LPC-were negatively associated with persistent MSMP after adjustment for covariates (OR = 0.22 and 0.27, respectively). This study identified three novel lipid signatures of persistent MSMP, suggesting that lipid metabolism is involved in the pathogenesis of persistent pain.