Crucial involvement of actin filaments in celecoxib and morphine analgesia in a model of inflammatory pain

Abstract

Patrícia Paiva-Lima,1 Rafael M Rezende,1 Rômulo Leite,2 Igor DG Duarte,1 YS Bakhle,3 Janetti N Francischi11Department of Pharmacology, Laboratory of Inflammation and Pain, Biological Sciences Institute, Federal University of Minas Gerais, Brazil; 2Department of Pharmacology, Faculty of Pharmacy, Federal University of Ouro Preto, Minas Gerais, Brazil; 3Leukocyte Biology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UKBackground: 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.Keywords: hypoalgesia, celecoxib, morphine, cytoskeleton, actin, cyclo-oxygenases