Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Oxidoreductases / antagonists & inhibitors
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Animals
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Arginine / administration & dosage
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Arginine / analogs & derivatives*
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Arginine / pharmacology
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Cycloleucine / administration & dosage
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Cycloleucine / analogs & derivatives
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Cycloleucine / pharmacology
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Hemoglobins / administration & dosage
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Hemoglobins / pharmacology*
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Hydroxylamine
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Hydroxylamines / administration & dosage
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Hydroxylamines / pharmacology
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Hyperalgesia / physiopathology*
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Ibotenic Acid / administration & dosage
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Ibotenic Acid / analogs & derivatives
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Ibotenic Acid / pharmacology
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Injections, Spinal
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Kainic Acid / administration & dosage
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Kainic Acid / pharmacology
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Male
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Mice
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Mice, Inbred ICR
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N-Methylaspartate / pharmacology*
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NG-Nitroarginine Methyl Ester
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Neurotoxins / pharmacology
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase
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Nitroprusside / administration & dosage
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Nitroprusside / pharmacology
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Spinal Cord / drug effects
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Spinal Cord / physiology*
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Spinal Cord / physiopathology
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Time Factors
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Substances
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Hemoglobins
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Hydroxylamines
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Neurotoxins
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Cycloleucine
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1-amino-1,3-dicarboxycyclopentane
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Nitroprusside
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Ibotenic Acid
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Hydroxylamine
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Nitric Oxide
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N-Methylaspartate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Arginine
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Nitric Oxide Synthase
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Amino Acid Oxidoreductases
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Kainic Acid
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NG-Nitroarginine Methyl Ester