Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition.
Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as the primary mechanism by which these agents produce a selective attenuation of pain (analgesia). NSAIDs are now shown to exert a direct spinal action by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of spinal glutamate and substance P receptors. These findings demonstrate that the analgesic effects of NSAIDs can be dissociated from their anti-inflammatory actions. Spinal prostanoids are thus critical for the augmented processing of pain information at the spinal level.
Malmberg
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Department of Anesthesiology, University of California-San Diego, La Jolla 92093-0818.
Yaksh
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007278:Injections, Spinal; D016202:N-Methylaspartate / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D011810:Quinoxalines; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D007051:Ibotenic Acid; D013373:Substance P; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011451:Prostaglandin-Endoperoxide Synthases