RESUMO
BACKGROUND: Celecoxib exerted analgesic effects (hypoalgesia) reversed by opioid receptor antagonists in a model of inflammatory pain. To analyze this celecoxib-induced hypoalgesia further, we assessed the effects of several disruptors of cytoskeletal components in our model of inflammation. METHODS: Hyperalgesia to mechanical stimuli was induced in rat hind paws by intraplantar injection of carrageenan and measured using the Randall-Selitto method over the next 8 hours. The effects of systemic pretreatment with celecoxib and a range of cytoskeletal disruptors (colchicine, nocodazole, cytochalasin B, latrunculin B, acrylamide, each given by intraplantar injection) on carrageenan-induced hyperalgesia were similarly investigated. Morphine and other selective cyclo-oxygenase 1 (SC-560), cyclo-oxygenase 2 (SC-236), and nonselective cyclo-oxygenase (indomethacin) inhibitors were also tested under similar conditions. RESULTS: None of the cytoskeletal disruptors affected the peak intensity of carrageenan-induced hyperalgesia, and its duration was increased only by nocodazole and colchicine. Pretreatment with celecoxib 30 minutes before carrageenan reversed the hyperalgesia and raised the nociceptive threshold (hypoalgesia). All analgesic effects of celecoxib were blocked by nocodazole, colchicine, cytochalasin B, and latrunculin B. Pretreatment with morphine also induced hypoalgesia in carrageenan-inflamed paws, an effect reversed by colchicine and cytochalasin B. However, the analgesic effects of indomethacin were not reversed by disruption of actin filaments with cytochalasin B or latrunculin B. CONCLUSION: These data strengthen the correlation between cytoskeletal structures and the processes of pain and analgesia.
RESUMO
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.
