Involvement of nitric oxide in clonidine-induced spinal analgesia.
BACKGROUND
The chronic pain relieving effects following spinal administration of clonidine are probably connected to alpha2-adrenoreceptor-induced augmented synthesis of nitric oxide (NO) in the spinal cord. In contrast, when acute pain is considered, the possible role of NO is still speculative. The aim of the present study was to explore the role of NO in acute pain relief following intraspinal administration of clonidine.


METHODS
We used the mouse tail-flick model of acute pain. Spinal injections of the following agents and their combinations were administered: 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).


RESULTS
A 95% analgesic response was achieved with 2.0 microg clonidine. L-Arginine produced analgesia, and L-arginine administration followed by clonidine resulted in a pronounced synergistic analgesic effect. This synergistic effect was attenuated by L-NAME. Pre-treatment with MB decreased and nitroglycerine administration did not affect the clonidine-induced analgesia.


CONCLUSIONS
NO may be involved in the mediation of the acute pain relieving effects of intraspinally administered clonidine. Further research is warranted to establish the potential benefits and possibility for incorporation of NO promoting agents in therapeutic regional pain regimens.
Aronov
Stela
S
Laboratory for Research in Anesthesia, Pain, and Neuroscience, 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; D003000:Clonidine / Q000008:administration & dosage*; D007278:Injections, Spinal; 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
D000700:Analgesics; D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D003000:Clonidine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester