INHIBITION OF NOCICEPTION-INDUCED SPINAL SENSITIZATION BY ANESTHETIC AGENTS

Background: Subcutaneous injection of dilute formalin in the hind paw of the rat produces a biphasic nociceptive response. Initial C-fiber a ctivity is accompanied by flinching of the paw for about 5 min (phase 1), followed by cessation of activity and resumption of flinching begi nning 15 min after injection and lasting about 40 min or more (phase 2 ). The second phase depends on changes in dorsal horn cell function th at occur shortly after the initial C-fiber discharge. It was previousl y shown that isoflurane, administered during phase 1, reduced phase 2 activity, but a combination of isoflurane and nitrous oxide given thro ughout phase 1 did not suppress spinal sensitization. The same model w as used to determine the effects of several inhalation and intravenous anesthetic agents on phase 2 of the formalin test. Methods: The forma lin test was carried out on male Sprague-Dawley rats. Animals anesthet ized briefly with halothane to facilitate formalin injection, were com pared to animals that received 1 MAC anesthesia from 5 min before to 6 min after formalin injection using halothane, enflurane, isoflurane, desflurane, or 70% N2O, or a combination of nitrous oxide plus 1 MAC h alothane. Animals that were given intravenous saline immediately befor e injection of formalin were compared to animals given either 20 mg/kg intravenous thiopental just before formalin injection or 10 mg/kg int ravenous propofol just before and 3 mg/kg immediately after formalin i njection, Flinches/minute were counted at 1 and 5 min after formalin i njection and thereafter at 5-min intervals for 1 h. The total of 1- an d 5-min flinches were considered phase 1 activity and the total of 10- 60-min flinches were considered phase 2. Total phase 2 activity was co mpared between groups using one-way analysis of variance. Results: Ani mals that received halothane, enflurane, isoflurane, desflurane, or ni trous oxide during phase 1 demonstrated a significant decrease in phas e 2 activity when compared to controls, while those that received a co mbination of nitrous oxide and halothane exhibited no difference. Anim als that received intravenous thiopental anesthesia during phase 1 dem onstrated no difference in phase 2 activity when compared to controls, whereas those that received propofol during phase 1 demonstrated a si gnificant decrease of phase 2 activity. Conclusions: Volatile anesthet ics or nitrous oxide significantly suppress spinal sensitization, wher eas the combination of nitrous oxide plus halothane causes no suppress ion. Thiopental does not affect spinal sensitization, whereas propofol causes significant suppression. These results may have important impl ications regarding the development of postoperative pain.