Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

Abstract

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.