Activation of fibroblast growth factor receptor by axotomy, through downstream p38 in dorsal root ganglion, contributes to neuropathic pain.
The possible involvement of fibroblast growth factor receptor (FGFR) activation in the dorsal root ganglion (DRG) was examined following peripheral nerve injury in the rat. Ligation of the sciatic nerve down-regulated FGFR2, -3 and -4 mRNA; however, the expression of FGFR1 mRNA showed no change. Activation of FGFR was examined by immunohistochemistry using an antibody of the phosphorylated form of FGFR1-4. Ligation of the sciatic nerve produced phosphorylation of FGFR in the L4 and 5 DRG ipsilateral to the injury, starting at 3 days after the lesion and persisting for more than 30 days. Substantial activation of FGFR was observed, mainly in unmyelinated small DRG neurons that co-expressed phosphorylated p38 mitogen-activated protein kinase (MAPK). Continuous intrathecal infusion of the FGFR1 inhibitor, 3-[3-(2-carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone, reduced p38 MAPK phosphorylation in the DRG and pain-related behaviors in the partial sciatic nerve model rat without affecting on the activation of spinal glia cells (microglia and astrocyte). In the injured small DRG neurons, activation of FGFR1 may contribute to the generation of neuropathic pain by activating p38 MAPK.
Yamanaka
H
H
Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Obata
K
K
Kobayashi
K
K
Dai
Y
Y
Fukuoka
T
T
Noguchi
K
K
D000818:Animals; D019771:Axotomy / Q000379:methods; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010147:Pain Measurement; D010766:Phosphorylation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012585:Sciatica / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D048051:p38 Mitogen-Activated Protein Kinases