[Effects of fasudil on neuropathic pain-like state in mice].
The aim of the present study was to investigate the role of protein kinases within the spinal cord in the development of a neuropathic pain-like state induced by partial sciatic nerve ligation in mice. Thermal hyperalgesia induced by nerve ligation in mice was markedly suppressed by either repeated intrathecal (i.t.) pre-treatment or post-treatment with the selective protein kinase (PKC) inhibitor RO-32-0432 and the selective Rho kinase inhibitor Y-27632. In contrast, sciatic nerve ligation-induced thermal hyperalgesia was not observed by repeated i.t. pre-treatment with the selective PKA inhibitor KT5720. Interestingly, thermal hyperalgesia induced by nerve ligation in mice was significantly suppressed by repeated i.t. post-treatment with fasudil, which possesses the inhibitory effect of several protein kinases including PKC and Rho kinase. Collectively, these findings suggest that a long-lasting activation of PKC and RhoA/Rho kinase pathways in the spinal cord may be responsible for the development of thermal hyperalgesia induced by nerve ligation in mice. The present data raise the fascinating possibility that i.t. or epidural administration with fasudil may be useful for the treatment of neuropathic pain.
Shiokawa
Mitsuru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
Yamaguchi
Takanori
T
Narita
Minoru
M
Okutsu
Daiki
D
Nagumo
Yasuyuki
Y
Miyoshi
Kan
K
Suzuki
Masami
M
Inoue
Tadao
T
Suzuki
Tsutomu
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D004195:Disease Models, Animal; D007268:Injections, Epidural; D007278:Injections, Spinal; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; C049347:fasudil