Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 μg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 μg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 μg/paw) prevented the action of cafestol (80 μg/paw), whereas the aminopeptidase inhibitor bestatin (400 μg/paw) potentiated the antinociceptive effect of cafestol (40 μg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.