title: Lysophosphatidic acid as the initiator of neuropathic pain.
abstract: The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) biosynthesis. LPA(1) receptor activation causes demyelination and sprouting of dorsal root fibers, leading to an induction of synaptic reorganization underlying allodynia, in which innocuous (tactile) stimuli cause intense pain. The LPA(1) signal also initiates the up-regulation of Ca(v)α2δ1 in dorsal root ganglion and PKCγ in the dorsal horn, underlying mechanisms for characteristic neuropathic hyperalgesia in myelinated sensory (A-type) fibers. On the other hand, the LPA(3) receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPA biosynthesis. Thus, both the LPA(1) and LPA(3) receptors play key roles in the initiation step using a feed-forward system for neuropathic pain.
authors.affiliation: Division of Molecular Pharmacology and Neuroscience, Graduate School of Biomedical Sciences, Nagasaki University, Japan. ueda@nagasaki-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D008246:Lysophospholipids / Q000096:biosynthesis*; D017628:Microglia / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000293:injuries / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D011493:Protein Kinase C; C032881:lysophosphatidic acid; D002118:Calcium