title: An LPA species (18:1 LPA) plays key roles in the self-amplification of spinal LPA production in the peripheral neuropathic pain model.
abstract: BACKGROUND
  We previously reported that nerve injury-induced neuropathic pain is initiated by newly produced lysophosphatidic acid (LPA).
  
  
  RESULTS
  In this study, we developed a quantitative mass spectrometry for detecting LPA species by using Phos-tag. Following nerve injury, the levels of 18:1, 16:0 and 18:0 LPA in the spinal dorsal horn significantly increased at 3 h and declined at 6 h. Among them, 18:1 LPA level was the most abundant. In the same preparation, there were significant elevations in the activities of cytosolic phospholipase A2 (cPLA2) and calcium-independent phospholipase A2 (iPLA2), key enzymes for LPA synthesis, at 1 h, while there was no significant change in phospholipase A1 activity. Pharmacological studies revealed that NMDA and neurokinin 1 receptors, cPLA2, iPLA2 and microglial activation, as well as LPA1 and LPA3 receptors were all involved in the nerve injury-induced LPA production, and underlying cPLA2 and iPLA2 activations. In the cells expressing LPA1 or LPA3 receptor, the receptor-mediated calcium mobilization was most potent with 18:1 LPA, compared with 16:0 or 18:0 LPA. Moreover, the intrathecal injection of 18:1 LPA, but not 16:0 or 18:0 LPA, caused a spinal LPA production and neuropathic pain-like behavior.
  
  
  CONCLUSIONS
  These results suggest that 18:1 LPA is the predominant ligand responsible for LPA1 and LPA3 receptors-mediated amplification of LPA production through microglial activation.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.forename: Jun
authors.initials: J
authors.lastname: Nagai
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000818:Animals; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: C514153:1,3-bis(bis(pyridin-2-ylmethyl)amino)propan-2-ol; D008246:Lysophospholipids; D011725:Pyridines; D049368:Receptors, Lysophosphatidic Acid; D054510:Phospholipases A2, Cytosolic; C032881:lysophosphatidic acid