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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

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

J Neurochem. 2009 Apr;109(2):603-10.

PMID: 19222705

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 alpha(2)delta-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP355025240	Ki 16425		355025-24-0	Price

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