title: Dexmedetomidine exerts dose-dependent age-independent antinociception but age-dependent hypnosis in Fischer rats.
abstract: Dexmedetomidine (Dex), an alpha(2)-adrenoceptor agonist, is an effective analgesic and sedative drug in adults; however, little information is available about its efficacy in pediatric populations. Some anesthetics exhibit an age-dependent analgesic effect, e.g., nitrous oxide, being relatively ineffective in newborn rats. We investigated the analgesic and hypnotic efficacy of Dex using 6 cohorts of Fischer rats aged 7, 15, 19, 23, and 29 days and adults exposed to either Dex (10 or 50 microg/kg) or saline subcutaneously. Formalin plantar testing was used to mimic inflammatory pain, and its effect was assessed using immunohistochemical (c-Fos staining) and behavioral methods. The hypnotic action of Dex was assessed by loss of righting reflex. Formalin administration produced a typical nociceptive response in each age group; these nociceptive responses were significantly attenuated by Dex 50 microg/kg at all ages (P < 0.05), whereas Dex 10 microg/kg had little effect. Neonatal rats showed the greatest hypnotic sensitivity to Dex (P < 0.05).
authors.affiliation: Departments of Anaesthetics and Intensive Care and Biological Sciences, Imperial College London.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sanders
authors.forename: Mariangella
authors.initials: M
authors.lastname: Giombini
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Mahmuda
authors.initials: M
authors.lastname: Hossain
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
mesh_terms: D000367:Age Factors; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018712:Analgesics, Non-Narcotic; D006993:Hypnotics and Sedatives; D016760:Proto-Oncogene Proteins c-fos; D020927:Dexmedetomidine