Elevated 18:1 lysophosphatidylcholine contributes to neuropathic pain in peripheral nerve injury.

Abstract

Neuropathic pain is a maladaptive and chronic condition with limited effective treatments. Although recent studies have suggested that certain lipid metabolites, like lysophosphatidylcholine (LPC), may contribute to chronic pain, their specific roles and mechanisms remain unclear. This study investigated the role and mechanism of LPC(18:1), a lipid subtype, in neuropathic pain caused by nerve injury. Using a mouse model of spinal nerve ligation, LPC(18:1) levels were measured in serum, dorsal root ganglion (DRG), spinal cord (SC) and cerebrospinal fluid (CSF). Nociception was assessed using von Frey and Hargreaves' methods, while molecular analyses explored inflammatory pathways and oxidative stress. LPC(18:1) levels significantly increased in the serum, DRG and CSF after nerve injury. Administration of LPC(18:1) induced heightened pain responses and activated inflammatory pathways, including protein kinase C (PKC) and extracellular regulated protein kinase (ERK) in the DRG, as well as glial cells in the SC. The findings suggested that oxidative stress played a role in LPC(18:1) production, and its effects were mediated by G protein-coupled receptor 132 (GPR132). LPC(18:1) may serve as a potential biomarker and therapeutic target for managing neuropathic pain.