Antinociceptive activity of ricinoleic acid, a capsaicin-like compound devoid of pungent properties

The antinociceptive effect of ricinoleic acid ([R-(Z)]-12-hydroxy-9-octadec enoic acid) in comparison with capsaicin (trans-8-methyl-N-vanillyl-6-nonen amide) has been investigated in several "in vivo" tests. Acute topical appl ication of capsaicin, but not ricinoleic acid, produced by itself an hypera lgesic effect detected as a decrease in paw withdrawal latency in response to a painful (heat) stimulus in mice. Capsaicin, but not ricinoleic acid at any dose tested, showed an irritant effect in the wiping test in guinea pi g conjunctiva after local application and in the paw licking test in mice a fter intradermal injection. Whereas acute application of ricinoleic acid or capsaicin decreased paw withdrawal latency to heat in the presence of a pr e-existing inflammation (injection of carrageenan in the mouse paw), the re peated local treatment for 8 days with either compounds markedly increased paw withdrawal latency. In a chronic model of inflammation (complete Freund 's adjuvant arthritis in mice), the repeated topical and intradermal treatm ents with both ricinoleic acid and capsaicin increased paw withdrawal laten cy to heat, the antinociceptive effect of ricinoleic acid being more persis tent than that of capsaicin. Antinociceptive effect of 8 days of treatment with ricinoleic acid and capsaicin was observed in acetic acid-induced writ hing in mice, capsaicin-induced foot licking in mice and capsaicin-induced wiping movements in guinea pig conjunctiva. A decrease of substance P tissu e levels in the mouse paw was found after repeated treatment with ricinolei c acid. In conclusion, ricinoleic acid seems to be a new antinociceptive ag ent lacking the pungent and acute hyperalgesic properties of capsaicin. (C) 2000 Elsevier Science B.V. All rights reserved.