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

• Main Authors: Aoki Junken (Author), Chun Jerold (Author), Inoue Makoto (Author), Nagai Jun (Author), Uchida Hitoshi (Author), Ma Lin (Author), Ueda Hiroshi (Author)
• Format: Book
• Published: SAGE Publishing, 2009-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>We examined <it>in vivo </it>LPA-induced LPA production using a biological titration assay with B103 cells expressing LPA₁receptors. 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 LPA₁or LPA₂receptors. Similar time-related and LPA₃receptor-mediated production of LPA was observed following intrathecal administration of LPA. In an <it>in vitro </it>study using spinal cord slices, LPA-induced LPA production was also mediated by ATX and the LPA₃receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA₁or LPA₃receptors.</p> <p>Conclusion</p> <p>These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.</p>

Item Description

10.1186/1744-8069-5-64
1744-8069