Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse.
Intrathecal injection of N-methyl-D-aspartate (NMDA) induces a short duration hyperalgesia in mice. An inhibitor of nitric oxide synthase (NOS), N omega-nitro-L-arginine methyl ester (L-NAME), administered either systemically or intrathecally, blocked the NMDA-induced hyperalgesia. This effect was partially reversed by the NOS substrate, L-arginine. Intrathecal hemoglobin mimicked the effects of L-NAME. Intrathecal injection of the NO-donating compounds, sodium nitroprusside (SNP) and hydroxylamine, resulted in a hyperalgesia that lasted 3 h and was reduced by coadministration of hemoglobin. Thus, nitric oxide production appears to mediate NMDA-induced hypersensitivity and may contribute to other forms of centrally induced hyperalgesia.
Kitto
K F
KF
Department of Pharmacology, Graduate Program in Neuroscience, University of Minnesota, Minneapolis 55455.
Haley
J E
JE
Wilcox
G L
GL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003515:Cycloleucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology*; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D007278:Injections, Spinal; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D006454:Hemoglobins; D006898:Hydroxylamines; D009498:Neurotoxins; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D009599:Nitroprusside; D007051:Ibotenic Acid; D019811:Hydroxylamine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester