Nitric oxide mediates allodynia induced by intrathecal administration of prostaglandin E2 or prostaglandin F2 alpha in conscious mice.
We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) E2 or PGF2 alpha in conscious mice induced allodynia through a pathway that includes the glutamate receptor system. Allodynia induced by PGE2 and PGF2 alpha was blocked by antagonists for NMDA and metabotropic glutamate receptor subtypes, respectively. In the present study, we examined the possibility for the involvement of nitric oxide (NO) in the PG-evoked allodynia. Allodynia was assessed once every 5 min by light stroking of the flank of mice with a paintbrush. Intrathecal administration of L-arginine, a substrate of nitric oxide synthase (NOS), in conscious mice resulted in allodynia. Dose dependency of L-arginine for allodynia showed a bell-shaped pattern (1-10 micrograms/mouse). The maximal allodynic effect was observed with 5.0 micrograms at 10-15 min after i.t. injection, similar in time course and magnitude to that induced by L-glutamate. L-Arginine-induced allodynia was dose-dependently reduced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) and the soluble guanylate cyclase inhibitor methylene blue with IC50 values of 7.68 and 8.70 pg/mouse, respectively. PGE2-induced allodynia was also dose-dependently inhibited by L-NAME and methylene blue with IC50 values of 94.7 and 74.9 pg/mouse. PGF2 alpha-induced allodynia was inhibited by methylene blue with an IC50 value of 40.6 pg/mouse, but not by L-NAME at doses up to 1.0 ng.(ABSTRACT TRUNCATED AT 250 WORDS)
Minami
Toshiaki
T
Department of Anesthesiology, Osaka Medical College, Takatsuki Japan Department of Cell Biology, Osaka Bioscience Institute, Suita Japan Department of Medical Chemistry, Kansai Medical University, Moriguchi Japan.
Nishihara
Isao
I
Ito
Seiji
S
Sakamoto
Kazuichi
K
Hyodo
Masayoshi
M
Hayaishi
Osamu
O
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects*
D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D001120:Arginine; D015237:Dinoprost; D015232:Dinoprostone; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester