title: Crucial involvement of actin filaments in celecoxib and morphine analgesia in a model of inflammatory pain.
abstract: 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.
  
  
  CONCLUSIONS
  These data strengthen the correlation between cytoskeletal structures and the processes of pain and analgesia.
authors.affiliation: Department of Pharmacology, Laboratory of Inflammation and Pain, Biological Sciences Institute, Federal University of Minas Gerais, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Paiva-Lima
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Rezende
authors.forename: Rômulo
authors.initials: R
authors.lastname: Leite
authors.forename: Igor Dg
authors.initials: ID
authors.lastname: Duarte
authors.forename: Ys
authors.initials: Y
authors.lastname: Bakhle
authors.forename: Janetti N
authors.initials: JN
authors.lastname: Francischi