Cerebroventricular injection of clonidine causes analgesia mediated by a nitrogen pathway.
Whereas neuroaxially administered clonidine produces analgesia partially mediated by alpha2-adrenoceptor-induced augmented synthesis of nitric oxide (NO), the central mechanisms by which clonidine produces its antinociceptive effects are still speculative. We used the tail-flick model of acute pain in mice to further explore the role of NO in mediating clonidine-induced central analgesia. Cerebroventricular administration of the following agents was studied: clonidine, L-arginine (NO precursor), the NO production inhibitor nitro-L-arginine-methyl ester (L-NAME), the NO antagonist methylene blue (MB), and nitroglycerine (NO-releasing agent). Analgesic response was achieved with clonidine and L-arginine. Simultaneous administration of L-arginine and clonidine produced no additive analgesic effect. Prior administration of L-NAME or MB partially abolished the clonidine-induced analgesic effect, whereas nitroglycerine administration did not affect it. NO may be involved in the mediation of the central antinociceptive effects of clonidine. Further investigation is necessary to determine the possible role of NO-promoting agents in analgesia when co-administered with clonidine.
Aronov
Stella
S
Laboratory for Anesthesia, Pain, and Neural Research, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Ben-Abraham
Ron
R
Givati-Divshi
Dafna
D
Katz
Yeshayahu
Y
D000208:Acute Disease; D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D002552:Cerebral Ventricles; D003000:Clonidine / Q000008:administration & dosage*; D007267:Injections; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D005996:Nitroglycerin / Q000008:administration & dosage; D010146:Pain / Q000517:prevention & control; D011897:Random Allocation
D000700:Analgesics; D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D003000:Clonidine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester