Cannabinoids and muscular pain. Effectiveness of the local administration in rat

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 (CB1) and JWH 015 (CB2); AM 251 (CB1) and AM 630 (CB2) were used as selective antagonists. Results: In the masseter pain model, both systemic (intraperitoneal) and local (intramuscular) administration of CB1 and CB2 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, CB1 and CB2 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.