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.
ASJC Scopus subject areas
- Molecular Medicine
- Cellular and Molecular Neuroscience
- Anesthesiology and Pain Medicine