Hyperalgesia Mediated by Spinal Glutamate or Substance P Receptor Blocked by Spinal Cyclooxygenase Inhibition

• Published in: Science (American Association for the Advancement of Science) Vol. 257; no. 5074; pp. 1276 - 1279
• Main Authors: Malmberg, A. B., Yaksh, T. L.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 28-08-1992
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione; Agonists; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Analgesia; Analgesics; Biological and medical sciences; Dizocilpine Maleate - pharmacology; Dosage; Dose-Response Relationship, Drug; Glutamates - physiology; Glutamic Acid; Hyperalgesia; Hyperalgesia - drug therapy; Hyperalgesia - physiopathology; Ibotenic Acid - analogs & derivatives; Ibotenic Acid - pharmacology; Injections, Spinal; Medical sciences; Mental stimulation; N-Methylaspartate - pharmacology; Neuropharmacology; Nonsteroidal anti-inflammatory agents; Nonsteroidal anti-inflammatory drugs; Pain; Pharmacology. Drug treatments; Physiological aspects; Prostaglandin-Endoperoxide Synthases - physiology; Prostaglandins; Quinoxalines - pharmacology; Rats; Receptors; Receptors, Neurokinin-1; Receptors, Neurotransmitter - physiology; Receptors, Tachykinin; Substance P - pharmacology; Unmyelinated nerve fibers; Non steroidal antiinflammatory agent; Analgesia; Spinal cord; Pain; Prostaglandin; Substance P; Arachidonic acid derivatives; Central nervous system; Glutamate receptor; Mechanism of action
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1381521

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.