Involvement of nitric oxide in clonidine-induced spinal analgesia

Stela Aronov, Ron Ben-Abraham, Dafha Givati-Divshi, Yeshayahu Katz

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background: The chronic pain relieving effects following spinal administration of clonidine are probably connected to α2- 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 μg 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. Pretreatment 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.

Original languageEnglish
Pages (from-to)41-53
Number of pages13
JournalDrug Metabolism and Drug Interactions
Issue number1
StatePublished - 2005
Externally publishedYes


  • Analgesia
  • Clonidine
  • Mouse
  • Nitric oxide
  • Spinal injection
  • Tail-flick


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