Recent advances in understanding of various chronic pain mechanisms through lysophosphatidic acid (LPA) receptor signaling

Recent studies revealed that another subtype LPA3 receptor plays a crucial role in neuropathic pain mechanisms in terms of LPA biosynthesis. Nerve injury and intrathecal administration of LPA increased the levels of lysophosphatidylcholine (LPC) and LPA in the spinal dorsal horn and dorsal root with peaks at 1 - 2 h. We obtained the evidence for in vitro LPA biosynthesis in spinal dorsal horn and dorsal root as well as in vivo one. In these studies we successfully identified the species of LPC and LPA molecules by use of Mass Spectrometery. Major species are the molecules with lipid chain 16:0, 18:0 or 18:1, and their contents were all time-dependently increased by nerve injury. Interestingly, there was an LPA-induced amplification of LPA biosynthesis through an activation of LPA3 receptor and microglia. The microglial involvement was found to play key roles as an initiation of neuropathic pain mechanisms including LPA3-mediated amplification of LPA biosynthesis.