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Published in: Molecular Pain 1/2009

Open Access 01-12-2009 | Research

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

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

Published in: Molecular Pain | Issue 1/2009

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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 LPA1 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 LPA3, but not LPA1 or LPA2 receptors. Similar time-related and LPA3 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 LPA3 receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA1 or LPA3 receptors.

Conclusion

These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.
Appendix
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Metadata
Title
Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: an initiator of nerve injury-induced neuropathic pain
Authors
Lin Ma
Hitoshi Uchida
Jun Nagai
Makoto Inoue
Jerold Chun
Junken Aoki
Hiroshi Ueda
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-5-64

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