Curcumin induces peripheral antinociception by opioidergic and cannabinoidergic mechanism: Pharmacological evidence.

Background: Curcumin is one of the compounds present in plants of the genus Curcuma sp., being very used not only as condiment but also with medicinal purposes. As an analgesic, papers highlight the efficacy of curcumin in the treatment of various types of pain.

Aims: In this study we evaluated the peripheral antinociceptive effect of curcumin and by which mechanisms this effect is induced.

Main Methods: The mice paw pressure test was used on animals which had increased pain sensitivity by intraplantar injection of carrageenan. All the drugs were administered in the right hind paw.

Key Findings: Curcumin was administered to the right hind paw animals induced antinociceptive effect. Non -selective antagonist of opioid receptors naloxone reverted the antinociceptive effect induced by curcumin. Selective antagonists for μ, δ and κ opioid receptors clocinnamox, naltrindole and nor- binaltorphimine, respectively, reverted the antinociceptive effect induced by curcumin. Bestatin, enkephalinases inhibitor that degrade peptides opioids, did not change the nociceptive response. Selective antagonists for CB and CB cannabinoid receptors, AM251 and AM630, respectively, reversed the antinociceptive effect induced by curcumin. The MAFP inhibitor of the enzyme FAAH which breaks down anandamide, JZL184, enzyme inhibitor MAGL which breaks down the 2-AG, as well as the VDM11 anandamide reuptake inhibitor potentiated the antinociceptive effect of curcumin.

Significance: These results suggest that curcumin possibly peripheral antinociception induced by opioid and cannabinoid systems activation and possibly for endocannabinoids and opioids release.