Comparative Analysis of Lysophosphatidic Acid Levels in Fibromyalgia and Other Painful Conditions in Female Patients.

BACKGROUND: Previous work found a decrease in lysophosphatidylcholines (LPCs) in fibromyalgia (FM) serum, prompting the hypothesis that this decrease could be due to increased conversion of LPC to lysophosphatidic acid (LPA) through autotaxin (ATX). LPA has pronociceptive functions, and increased LPA levels could modulate FM pain. METHODS: This study quantified LPA levels in serum and lumbar cerebrospinal fluid (CSF) and serum ATX levels in FM patients, comparing with healthy controls (HCs), osteoarthritis (OA), degenerative disc disease (DDD) and lumbar disc herniation (LDH) patients. RESULTS: We found increased serum LPA levels in FM and OA patients, with no changes in FM lumbar CSF. Unexpectedly, a positive correlation between serum LPA and conditioned pain modulation was observed in FM patients, while LPA levels were correlated with pain intensity and Knee Injury and Osteoarthritis Outcome Scores in OA. Serum ATX levels in FM patients were comparable to those in HC but correlated significantly with FM LPA levels (in one cohort), as well as with pain duration and the maximal weekly pain intensity. CONCLUSIONS: This study suggests that increased LPA levels play distinct roles in FM and OA patients. In FM, LPA levels were linked to less impaired inhibitory pain pathways, while LPA levels in OA correlated with pain intensity and knee-related impairment. ATX levels in FM serum are associated with pain intensity and duration. These findings underscore the complex role of LPA and ATX in FM pathophysiology. Future studies are essential to clarify LPA's specific roles and to develop therapies. SIGNIFICANCE STATEMENT: This study provides novel insights into the role of LPA in FM and other chronic pain conditions. Although ATX levels were unchanged in FM, a positive correlation between serum ATX and LPA supports the role of ATX in LPA conversion. These findings suggest complex lipid dysregulation in FM, with LPA potentially modulating pain pathways. Further research is needed to clarify LPA's role and its potential as a biomarker or therapeutic target.