Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: An initiator of nerve injury-induced neuropathic pain

Lin Ma, Hitoshi Uchida, Jun Nagai, Makoto Inoue, Jerold Chun, Junken Aoki, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Background: We previously reported that intrathecal injection of lysophosphatidylcholine (LPC) induced neuropathic pain through activation of the lysophosphatidic acid (LPA)-1 receptor, possibly via conversion to LPA by autotaxin (ATX).Results: We examined in vivo LPA-induced LPA production using a biological titration assay with B103 cells expressing LPA 1 receptors. Intrathecal administration of LPC caused time-related production of LPA in the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, spinal nerve or sciatic nerve. LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA 3, but not LPA 1 or LPA 2 receptors. Similar time-related and LPA 3 receptor-mediated production of LPA was observed following intrathecal administration of LPA. In an in vitro study using spinal cord slices, LPA-induced LPA production was also mediated by ATX and the LPA 3 receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA 1 or LPA 3 receptors.Conclusion: These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.

Original languageEnglish
Article number64
JournalMolecular Pain
Volume5
DOIs
Publication statusPublished - 2009 Nov 13

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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