Evidence for lysophosphatidic acid 1 receptor signaling in the early phase of neuropathic pain mechanisms in experiments using Ki-16425, a lysophosphatidic acid 1 receptor antagonist

Lin Ma, Misaki Matsumoto, Weijiao Xie, Makoto Inoue, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review

Abstract

Lysophosphatidic acid is a bioactive lipid mediator with neuronal activities. We previously reported a crucial role for lysophosphatidic acid 1 receptor-mediated signaling in neuropathic pain mechanisms. Intrathecal administration of lysophosphatidic acid (1 nmol) induced abnormal pain behaviors, such as thermal hyperalgesia, mechanical allodynia, A-fiber hypersensitization, and C-fiber hyposensitization, all of which were also observed in partial sciatic nerve injury-induced neuropathic pain. Ki-16425 (30 mg/kg, i.p.), a lysophosphatidic acid 1 receptor antagonist, completely blocked lysophosphatidic acid-induced neuropathic pain-like behaviors, when administered 30 min but not 90 min before lysophosphatidic acid injection, suggesting that Ki-16425 is a short-lived inhibitor. The blockade of nerve injury-induced neuropathic pain by Ki-16425 was maximum as late as 3 h after the injury but not after this critical period. The administration of Ki-16425 at 3 h but not at 6 h after injury also blocked neurochemical changes, including up-regulation of voltage-gated calcium channel α2δ-1 subunit expression in dorsal root ganglion and reduction of substance P expression in the spinal dorsal horn. All of these results using Ki-16425 suggest that lysophosphatidic acid 1 receptor-mediated signaling which underlies the development of neuropathic pain works at an early stage of the critical period after nerve injury.

Original languageEnglish (US)
Pages (from-to)603-610
Number of pages8
JournalJournal of Neurochemistry
Volume109
Issue number2
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • Antagonist
  • Lysophosphatidic acid
  • Neuropathic pain
  • Substance P
  • Voltage-gated calcium channel

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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