Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain

Naunyn Schmiedebergs Arch Pharmacol. 2009 Jun;379(6):627-36. doi: 10.1007/s00210-008-0386-4. Epub 2009 Jan 18.


Cannabinoid receptor (CB) agonists are known to attenuate allodynia in a range of pain models, but their long-term effects and their mechanisms of action are controversial. The present study compares the antiallodynic effects of long-term treatment with a mixed CB1/CB2 (WIN55,212-2) and a selective CB2 (GW405833) cannabinoid receptor agonist and correlates these effects with their influences on spinal cord (SC) glial activation. The substances were applied daily in a rat neuropathic pain model. Tactile allodynia was assessed, and the development of gliosis was illustrated with immunohistochemical methods. Both substances reduced mechanical allodynia. Their analgesic effect was accompanied by a significant reduction in reactive gliosis and cathepsins (CAT) X and S expression. A daily injection of either substance for 8 days was sufficient to induce a sustained antiallodynic effect, which persisted up to 6 days after the last injection. The re-appearance of mechanical allodynia after this period was associated with a breakout of a strong gliotic response in the lumbar SC. Our results emphasize the therapeutic efficacy of cannabinoid receptor agonists and their inhibitory effects on the formation of gliosis.

Publication types

  • Comparative Study

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Benzoxazines / therapeutic use
  • Cannabinoid Receptor Agonists*
  • Cannabinoids / therapeutic use
  • Disease Models, Animal*
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Male
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • Naphthalenes / therapeutic use
  • Neuralgia / drug therapy*
  • Neuralgia / pathology
  • Pain / drug therapy*
  • Pain / pathology
  • Rats
  • Rats, Wistar
  • Receptors, Cannabinoid / physiology


  • 1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-(2-(mopholin-4-yl)ethyl)-1H-indole
  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Cannabinoids
  • Indoles
  • Morpholines
  • Naphthalenes
  • Receptors, Cannabinoid
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone