title: N-Methyl-D-aspartate receptor modulators block hyperalgesia induced by acute low-dose morphine.
abstract: 1. Following opioid-induced antinociception in mice, hyperalgesic responses may be observed. The present study was designed to evaluate the effect of different N-methyl-d-aspartate (NMDA) receptor modulators (magnesium, dextromethorphan, d-serine) on the development of morphine-induced hyperalgesia in mice. The tail-flick test was used to assess the effects of morphine alone and in combination with the NMDA receptor modulators. 2. Administration of a single low dose (2 mg/kg) of morphine to mice produced antinociception that was followed by hyperalgesia. 3. Administration of magnesium sulphate (5 mg/kg) and d-serine (10 mg/kg) alone produced a transient antinociceptive response, whereas dextromethorphan (10 mg/kg) alone produced a prolonged antinociceptive response that had a relatively delayed onset after 4 h. 4. When coadministered with morphine, the NMDA receptor blockers magnesium (2 mg/kg) and dextromethorphan (2 and 5 mg/kg) and the NMDA receptor agonist d-serine (2, 5 and 10 mg/kg), maintained the duration of the antinociceptive response to morphine and inhibited the development of the hyperalgesic response. Coadministration of dextromethorphan (10 mg/kg) with morphine produced antinociception at 30-120 min and at 4-24 h. 5. The results of the present study suggest that coadministration of low-dose NMDA receptor antagonists, as well as the NMDA receptor agonist d-serine, with morphine can inhibit morphine-induced hyperalgesia.
authors.affiliation: Department of Pharmacology, Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi, India. lkg71@rediffmail.com
authors.forename: L K
authors.initials: LK
authors.lastname: Gupta
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.forename: C D
authors.initials: CD
authors.lastname: Tripathi
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003915:Dextromethorphan / Q000494:pharmacology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012694:Serine / Q000494:pharmacology
chemical_list: D000700:Analgesics; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D003915:Dextromethorphan; D008278:Magnesium Sulfate; D009020:Morphine