TY - JOUR
T1 - Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid
T2 - An initiator of nerve injury-induced neuropathic pain
AU - Ma, Lin
AU - Uchida, Hitoshi
AU - Nagai, Jun
AU - Inoue, Makoto
AU - Chun, Jerold
AU - Aoki, Junken
AU - Ueda, Hiroshi
PY - 2009/11/13
Y1 - 2009/11/13
N2 - 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.
AB - 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.
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U2 - 10.1186/1744-8069-5-64
DO - 10.1186/1744-8069-5-64
M3 - Article
C2 - 19912636
AN - SCOPUS:75549089548
SN - 1744-8069
VL - 5
JO - Molecular Pain
JF - Molecular Pain
M1 - 64
ER -