Involvement of LPA₁receptor signaling in the reorganization of spinal input through Abeta-fibers in mice with partial sciatic nerve injury

• Main Authors: Chun Jerold, Matsumoto Misaki, Xie Weijiao, Ueda Hiroshi
• Format: Article
• Language: English
• Published: SAGE Publishing 2008-10-01
• Series: Molecular Pain
• Online Access: http://www.molecularpain.com/content/4/1/46

<p>Abstract</p> <p>Lysophosphatidic acid receptor subtype LPA₁is 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 LPA₁signaling 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 LPA₁receptor knock-out (<it>Lpar1</it>^-/-) mice, further supported by quantitative analyses of pERK-positive cells. These results suggest that LPA₁receptor-mediated signaling mechanisms also participate in functional cross-talk between Aβ- and C- or Aδ-fibers.</p>