title: Pre-emptive morphine treatment abolishes nerve injury-induced lysophospholipid synthesis in mass spectrometrical analysis.
abstract: We have previously demonstrated that lysophosphatidic acid (LPA) production in the spinal cord following partial sciatic nerve injury (SCNI) and its signaling initiate neuropathic pain. In order to examine whether LPA production depends on the intense nociceptive signal, we have attempted to see suppression by pre-emptive treatment with centrally administered morphine, which mainly inhibits nociceptive signal at the level of spinal cord. In the present study, we developed a quantitative mass spectrometry assay to simultaneously analyze several species of lysophosphatidyl choline (LPC). The levels of 16:0-, 18:0- and 18:1-LPC in the spinal cord and dorsal root were maximally increased at 75 min after SCNI and then declined, as LPC is converted to LPA by autotaxin (ATX). In atx(+/-)-mice, on the other hand, these levels were similar to wild-type mice at 75 min, but maximal at 120 min, suggesting that this difference is partly due to the low conversion of LPC to LPA in atx(+/-)-mice. When morphine was centrally administered before SCNI, the injury-induced increase of LPC was completely abolished. These results suggest that LPC (or LPA) is produced by injury-induced nociceptive signal, which is effectively and pre-emptively suppressed by central morphine, possibly through known descending anti-nociceptive pathways.
authors.affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000818:Animals; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008246:Lysophospholipids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009020:Morphine / Q000008:administration & dosage*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D016896:Treatment Outcome
chemical_list: D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D009020:Morphine; C032881:lysophosphatidic acid