title: Cannabinoids and muscular pain. Effectiveness of the local administration in rat.
abstract: BACKGROUND
  Pain associated with musculoskeletal disorders can be difficult to control and the incorporation of new approaches for its treatment is an interesting challenge. Activation of cannabinoid (CB) receptors decreases nociceptive transmission in acute, inflammatory and neuropathic pain states; however, although the use of cannabis derivatives has been recently accepted as a useful alternative for the treatment of spasticity and pain in patients with multiple sclerosis, the effects of CB receptor agonists in muscular pain have hardly been studied.
  
  
  METHODS
  Here, we characterized the antinociceptive effect of non selective and selective CB agonists by systemic and local administration, in two muscular models of pain, masseter and gastrocnemius, induced by hypertonic saline (HS) injection. Drugs used were: the non-selective agonist WIN 55,212-2 and two selective agonists, ACEA (CB 1) and JWH 015 (CB 2); AM 251 (CB 1) and AM 630 (CB 2) were used as selective antagonists.
  
  
  RESULTS
  In the masseter pain model, both systemic (intraperitoneal) and local (intramuscular) administration of CB 1 and CB 2 agonists reduced the nociceptive behaviour induced by HS, whereas in the gastrocnemius model the local administration was more effective than systemic.
  
  
  CONCLUSIONS
  Our results provide evidence that both, CB 1 and CB 2 receptors can contribute to muscular antinociception and, interestingly, suggest that the local administration of CB agonists could be a new and useful pharmacological strategy in the treatment of muscular pain, avoiding adverse effects induced by systemic administration.
authors.affiliation: Departamento de Farmacología y Nutrición, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain. eva.sanchez@urjc.es
authors.forename: E Ma
authors.initials: EM
authors.lastname: Sánchez Robles
authors.forename: A
authors.initials: A
authors.lastname: Bagües Arias
authors.forename: Ma I
authors.initials: MI
authors.lastname: Martín Fontelles
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D059352:Musculoskeletal Pain / Q000188:drug therapy*; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use; D010147:Pain Measurement; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094023:iodopravadoline; C402944:JHW 015