Peri-MAC depression of a nociceptive withdrawal reflex is accompanied by reduced dorsal horn activity with halothane but not isoflurane

Background: Anesthetics act in the spinal cord to suppress movement evoked by a noxious stimulus, although the exact site is unknown. Methods: This study investigated sensorimotor processing in hind limb withdrawal reflexes, and effects of two general anesthetics, halothane and isoflurane, on simultaneously recorded responses of single dorsal horn neurons and hind limb withdrawal force, elicited by graded noxious thermal hind paw stimulation in rats. Minimum alveolar anesthetic concentration (MAC) needed to block gross movement to a supra-maximal mechanical stimulus was determined for each animal. Results: Between 0.9 and 1.1 MAC, halothane and isoflurane greatly reduced or abolished withdrawal force (79 and 89% reduction, respectively). Halothane (0.75-1.4 MAC) depressed heat-evoked neuronal responses in a concentration-related manner (41% reduction between 0.9 and 1.1 MAC averaged across all stimulus temperatures, P < 0.05) and decreased stimulus-response function slopes, with corresponding reductions in withdrawal force. In contrast, isoflurane did not reduce neuronal responses in the 0.75-1.4 MAC range and slightly facilitated responses (by 16%) when concentration increased from 0.9 to 1.1 MAC, despite a concurrent withdrawal force reduction. Anesthetic depression of heat-evoked withdrawal force correlated well with MAC determination using a supra-maximal mechanical stimulus. At sub-MAC anesthetic concentrations, some units exhibited firing rate changes that preceded and paralleled moment-to-moment changes in force during a given withdrawal. Conclusions: Halothane reduces noxious-evoked movement at least partly via depression of dorsal horn neurons, whereas isoflurane suppresses movement by an action at more ventral sites in the spinal cord.