Short report

Involvement of LPA₁ receptor signaling in the reorganization of spinal input through Abeta-fibers in mice with partial sciatic nerve injury

Weijiao Xie¹ , Misaki Matsumoto¹ , Jerold Chun² and Hiroshi Ueda¹

¹  Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan

²  Department of Molecular Biology, Helen L. Dorris Neuropsychiatric Disease Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND118, La Jolla, CA 92037, USA

author email corresponding author email

Molecular Pain 2008, 4:46doi:10.1186/1744-8069-4-46

Published:	15 October 2008

Abstract

Lysophosphatidic acid receptor subtype LPA₁ is crucial for the initiation of neuropathic pain and underlying changes, such as up-regulation of Ca²+ channel α₂δ-1 subunit in dorsal root ganglia (DRG), up-regulation of PKCγ in the spinal dorsal horn, and demyelination of dorsal root fibers. In the present study, we further examined the involvement of LPA₁ signaling in the reorganization of Aβ-fiber-mediated spinal transmission, which is presumed to underlie neuropathic allodynia. Following nerve injury, the phosphorylation of extracellular-signal regulated kinase (pERK) by Aβ-fiber stimulation was observed in the superficial layer of spinal dorsal horn, where nociceptive C- or Aδ-fibers are innervated, but not in sham-operated wild-type mice. However, the pERK signals were largely abolished in LPA₁ receptor knock-out (Lpar1^-/-) mice, further supported by quantitative analyses of pERK-positive cells. These results suggest that LPA₁ receptor-mediated signaling mechanisms also participate in functional cross-talk between Aβ- and C- or Aδ-fibers.