Pathogenic mechanisms of lipid mediator lysophosphatidic acid in chronic pain

A number of membrane lipid-derived mediators play pivotal roles in the initiation, maintenance, and regulation of various types of acute and chronic pain. Acute pain, comprising nociceptive and inflammatory pain warns us about the presence of damage or harmful stimuli. However, it can be efficiently reversed by opioid analgesics and anti-inflammatory drugs. Prostaglandin E-2 and I-2, the representative lipid mediators, are well-known causes of acute pain. However, some lipid mediators such as lipoxins, resolvins or endocannabinoids suppress acute pain. Various types of peripheral and central neuropathic pain (NeuP) as well as fibromyalgia (FM) are representatives of chronic pain and refractory owing to abnormal pain processing distinct from acute pain. Accumulating evidence demonstrated that lipid mediators represented by lysophosphatidic acid (LPA) are involved in the initiation and maintenance of both NeuP and FM in experimental animal models. The LPAR(1)-mediated peripheral mechanisms including dorsal root demyelination, Ca-v alpha 2 delta 1 expression in dorsal root ganglion, and LPAR(3)-mediated amplification of central LPA production via glial cells are involved in the series of molecular mechanisms underlying NeuP. This review also discusses the involvement of lipid mediators in emerging research directives, including itch-sensing, sexual dimorphism, and the peripheral immune system.

Automated summary

Membrane lipid-derived mediators play important roles in acute and chronic pain, with some mediators such as LPAR(1) and LPAR(3) involved in the molecular mechanisms of NeuP and FM. Acute pain, caused by mediators like prostaglandins, can be reversed by opioid analgesics and anti-inflammatory drugs, while chronic pain is refractory and difficult to treat.