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Open Access 01-12-2008 | Short report

Autotaxin, a synthetic enzyme of lysophosphatidic acid (LPA), mediates the induction of nerve-injured neuropathic pain

Authors: Makoto Inoue, Lin Ma, Junken Aoki, Jerold Chun, Hiroshi Ueda

Published in: Molecular Pain | Issue 1/2008

Abstract

Recently, we reported that lysophosphatidic acid (LPA) induces long-lasting mechanical allodynia and thermal hyperalgesia as well as demyelination and upregulation of pain-related proteins through one of its cognate receptors, LPA₁. In addition, mice lacking the LPA₁ receptor gene (lpa₁^-/- mice) lost these nerve injury-induced neuropathic pain behaviors and phenomena. However, since lpa₁^-/- mice did not exhibit any effects on the basal nociceptive threshold, it is possible that nerve injury-induced neuropathic pain and its machineries are initiated by LPA via defined biosynthetic pathways that involve multiple enzymes. Here, we attempted to clarify the involvement of a single synthetic enzyme of LPA known as autotaxin (ATX) in nerve injury-induced neuropathic pain. Wild-type mice with partial sciatic nerve injury showed robust mechanical allodynia starting from day 3 after the nerve injury and persisting for at least 14 days, along with thermal hyperalgesia. On the other hand, heterozygous mutant mice for the autotaxin gene (atx^+/-), which have 50% ATX protein and 50% lysophospholipase D activity compared with wild-type mice, showed approximately 50% recovery of nerve injury-induced neuropathic pain. In addition, hypersensitization of myelinated A

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- or Aδ-fiber function following nerve injury was observed in electrical stimuli-induced paw withdrawal tests using a Neurometer^®. The hyperalgesia was completely abolished in lpa₁^-/- mice, and reduced by 50% in atx^+/- mice. Taken together, these findings suggest that LPA biosynthesis through ATX is the source of LPA for LPA₁ receptor-mediated neuropathic pain. Therefore, targeted inhibition of ATX-mediated LPA biosynthesis as well as LPA₁ receptor and its downstream pathways may represent a novel way to prevent nerve injury-induced neuropathic pain.

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Title: Autotaxin, a synthetic enzyme of lysophosphatidic acid (LPA), mediates the induction of nerve-injured neuropathic pain
Authors: Makoto Inoue
Lin Ma
Junken Aoki
Jerold Chun
Hiroshi Ueda
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2008
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-4-6

At a glance: The STEP trials

Springer Medicine

Autotaxin, a synthetic enzyme of lysophosphatidic acid (LPA), mediates the induction of nerve-injured neuropathic pain

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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