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 LPA(1) is crucial for the initiation of neuropathic pain and underlying changes, such as up-regulation of Ca2+ channel alpha2delta-1 subunit in dorsal root ganglia (DRG), up-regulation of PKCgamma in the spinal dorsal horn, and demyelination of dorsal root fibers. In the present study, we further examined the involvement of LPA(1) signaling in the reorganization of Abeta-fiber-mediated spinal transmission, which is presumed to underlie neuropathic allodynia. Following nerve injury, the phosphorylation of extracellular-signal regulated kinase (pERK) by Abeta-fiber stimulation was observed in the superficial layer of spinal dorsal horn, where nociceptive C- or Adelta-fibers are innervated, but not in sham-operated wild-type mice. However, the pERK signals were largely abolished in LPA(1) receptor knock-out (Lpar1-/-) mice, further supported by quantitative analyses of pERK-positive cells. These results suggest that LPA(1) receptor-mediated signaling mechanisms also participate in functional cross-talk between Abeta- and C- or Adelta-fibers.
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan. dm07182c@cc.nagasaki-u.ac.jp
Weijiao
W
Xie
Misaki
M
Matsumoto
Jerold
J
Chun
Hiroshi
H
Ueda
D000818:Animals; D003711:Demyelinating Diseases; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005727:Ganglia, Spinal; D051379:Mice; D010766:Phosphorylation; D020671:Posterior Horn Cells; D049368:Receptors, Lysophosphatidic Acid / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D020426:Sciatic Neuropathy / Q000503:physiopathology*; D015398:Signal Transduction; D013127:Spinal Nerves; D009435:Synaptic Transmission
D049368:Receptors, Lysophosphatidic Acid; D048049:Extracellular Signal-Regulated MAP Kinases