To induce hyperalgesia, rat paws were treated with intraplantar prostaglandin E2 (PGE2, 2 ¦Ìg). Nociceptive thresholds to pressure (grams) were measured using an algesimetric apparatus 3 h following injection. Probabilities were calculated using ANOVA/Bonferroni's test, and values that were less than 5 % were considered to be statistically significant.
Administration of the cannabinoid agonist CB1 anandamide (12.5, 25 and 50 ¦Ìg/paw) and the cannabinoid agonist CB2 PEA (5, 10 and 20 ¦Ìg/paw) decreased the PGE2-induced hyperalgesia in a dose-dependent manner. The possibility of the higher doses of anandamide (50 ¦Ìg) and PEA (20 ¦Ìg) having a central or systemic effect was excluded because the administration of the drug into the contralateral paw did not elicit antinociception in the right paw. As expected, the antinociceptive effects induced by anandamide and PEA were blocked by the CB1 and CB2 receptor antagonists AM251 and AM630, respectively. The peripheral antinociception was induced by anandamide but not PEA and was dose-dependently inhibited by the CaCC blocker niflumic acid (8, 16 and 32 ¦Ìg).
These results provide the first evidence for the involvement of CaCCs in the peripheral antinociception induced by activation of the CB1 cannabinoid receptor.