Effect of cannabinoid receptor agonists on streptozotocin-induced hyperalgesia in diabetic neuropathy

Pharmacology. 2008;82(3):193-200. doi: 10.1159/000156485. Epub 2008 Sep 23.

Abstract

The effect of CB-1 and CB-2 receptor agonists, as well as an influence of a non-selective inhibitor of nitric oxide synthase (NOS), L-NOArg, and an inhibitor acting preferentially on cyclooxygenase-1 (COX-1), indomethacin, on the action of cannabinoid receptor agonists in a streptozotocin (STZ)-induced neuropathic model was investigated. When administered alone, a non-selective cannabinoid receptor agonist, WIN 55,212-2, a potentially selective CB-1 cannabinoid receptor agonist, Met-F-AEA, and a selective CB-2 cannabinoid receptor agonist, AM1241, dose-dependently reduced STZ-induced hyperalgesia. The results of the present study also demonstrated that inhibitors of COX and NOS increase antihyperalgesic activity of low doses of CB-1 and CB-2 receptor agonists. Hypothetical consequences of this phenomenon are discussed.

Publication types

  • Comparative Study

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacology
  • Animals
  • Arachidonic Acids / administration & dosage
  • Arachidonic Acids / pharmacology
  • Benzoxazines / administration & dosage
  • Benzoxazines / pharmacology
  • Cannabinoids / administration & dosage
  • Cannabinoids / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / physiopathology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Indomethacin / pharmacology
  • Male
  • Morpholines / administration & dosage
  • Morpholines / pharmacology
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB2 / agonists*
  • Streptozocin

Substances

  • 2-methylarachidonyl-2'-fluoroethylamide
  • AM 1241
  • Analgesics
  • Arachidonic Acids
  • Benzoxazines
  • Cannabinoids
  • Cyclooxygenase Inhibitors
  • Morpholines
  • Naphthalenes
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Nitroarginine
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Streptozocin
  • Nitric Oxide Synthase
  • Indomethacin