Lysophosphatidic acid3 receptor-mediated feed-forward production of lysophosphatidic acid : an initiator of nerve injury-induced neuropathic pain

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. Background Lysophosphatidylcholine (LPC, lysolecithin) is the most abundant lysophospholipid in the blood and tissues [1,2]. LPC, an important biologically active signaling molecule, is generated under specific physiological and pathological conditions, and exerts multiple effects in atherosclerosis and inflammatory diseases [3-9]. LPC is widely reported to possess demyelinating properties, and has been used to study the processes underlying demyelination and remyelination [10-15]. Moreover, recent eviPublished: 13 November 2009 Molecular Pain 2009, 5:64 doi:10.1186/1744-8069-5-64 Received: 26 August 2009 Accepted: 13 November 2009 This article is available from: http://www.molecularpain.com/content/5/1/64 © 2009 Ma et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.