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An LPA species (18:1 LPA) plays key roles in the self-amplification of spinal LPA production in the peripheral neuropathic pain model.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsLin Ma, Jun Nagai, Jerold Chun, Hiroshi Ueda
JournalMolecular pain (Mol Pain) Vol. 9 Pg. 29 (Jun 17 2013) ISSN: 1744-8069 [Electronic] United States
PMID23773289 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 1,3-bis(bis(pyridin-2-ylmethyl)amino)propan-2-ol
  • Lysophospholipids
  • Pyridines
  • Receptors, Lysophosphatidic Acid
  • Phospholipases A2, Cytosolic
  • lysophosphatidic acid
Topics
  • Animals
  • Lysophospholipids (chemistry, metabolism)
  • Male
  • Mice
  • Neuralgia (metabolism)
  • Neurons (metabolism)
  • Phospholipases A2, Cytosolic (metabolism)
  • Pyridines (chemistry)
  • Receptors, Lysophosphatidic Acid (metabolism)
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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