Dexmedetomidine exerts dose-dependent age-independent antinociception but age-dependent hypnosis in Fischer rats

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 mu g/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 mu g/kg at all ages (P < 0.05), whereas Dex 10 mu g/kg had little effect. Neonatal rats showed the greatest hypnotic sensitivity to Dex (P < 0.05).