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

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.