The involvement of nitric oxide in the analgesic effects of ketamine.
We investigated the contribution of NO-cyclic GMP (cGMP) pathway to the antinociceptive effects of ketamine in mice by using the nitric oxide synthase inhibitor, nitro(g)- L-arginine methyl ester (L-NAME). Intraperitoneal (i.p.) (1, 5 or 10 mg/kg) or intrathecal (i.th.) (10, 30 or 60 microg/mouse) administration of ketamine produced dose-dependent antinociceptive effects in the acetic acid-induced writhing and formalin tests but not in the tail-flick nor in hot-plate tests. Pretreatment of mice with L-NAME (10 mg/kg, i.p.) which produced no antinociception on its own, significantly inhibited the antinociceptive effect of ketamine (1, 5 or 10 mg/kg, i.p.). However, L-NAME (30 microg/mouse) was given intrathecally, it neither modified the antinociceptive effect of i.th. ketamine (10, 30 or 60 microg/mouse) nor did it produce an antinociceptive effect alone. These data suggest that the activation of the NO-cGMP pathway probably at the supraspinal level, but not spinal level, contributes to the antinociceptive effects of ketamine.
Bulutcu
Fusun
F
Department of Anesthesiology, Kadir Has University, Florance Nightingale Hospital, Istanbul, Turkey.
Dogrul
Ahmet
A
Güç
M Oguz
MO
D019342:Acetic Acid; D000778:Anesthetics, Dissociative / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde; D006358:Hot Temperature; D007649:Ketamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects
D000778:Anesthetics, Dissociative; D004791:Enzyme Inhibitors; D005557:Formaldehyde; D009569:Nitric Oxide; D007649:Ketamine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester