Volatile anesthetic effects on midbrain-elicited locomotion suggest that the locomotor network in the ventral spinal cord is the primary site for immobility

Volatile anesthetics act primarily in the spinal cord to abolish movement in response to noxious stimulation.1–3 However, anesthetic action does not seem to be uniform across different classes of neurons residing in different anatomical locations of the spinal cord. Slightly above and below minimum alveolar concentration (MAC) where noxious stimulus–evoked movement is abolished, isoflurane has little effect on nociceptive dorsal horn neurons4–8 recorded in vivo, whereas ventral horn neurons are depressed.9 Dorsal horn neurons are moderately suppressed by halothane.4,7,10,11 However, halothane depression of dorsal horn neurons was shown to be completely reversed by naloxone, whereas motor output suppression was only partially reversed.10 These data suggest that volatile anesthetic–induced immobility results largely from action in ventral spinal sites. Nevertheless, at sub-MAC concentrations, volatile anesthetics, including isoflurane, can reduce activity in dorsal horn neurons by 50%12—a perhaps necessary but not sufficient condition for immobility. Moreover, volatile anesthetics could modulate neurotransmitter release from dorsal horn neurons without changing their action potential firing rates. There is also evidence that some subclasses of nociceptive dorsal horn neurons, based on their functional and/or laminar location, are depressed by volatile anesthetics, whereas other neurons are unaffected. 11,13,14 Uncertainty about whether and to what degree a given dorsal horn neuron contributes to movement versus ascending nociceptive transmission per se further complicates current understanding of the mode of volatile anesthetic immobilizing action. Therefore, conclusions regarding the degree of dorsal horn involvement in anesthetic-induced immobility could are difficult to reach. However, it is possible to behaviorally dissect anesthetic immobilizing effects in the dorsal horn from those in the ventral horn using electrical microstimulation of the mesencephalic locomotor region (MLR), corresponding to the cuneiform and pedunculopontine nuclei.15 Electrical or chemical MLR stimulation elicits movement by activating spinal locomotor networks through a descending pathway that is similar across several, if not all, vertebrate classes. Descending locomotor activation from MLR-associated brain regions excites reticulospinal neurons in the ventromedial medulla, which in turn excite spinal lamina VII–VIII locomotor interneurons16 without activating (and in fact inhibiting) dorsal horn neurons,17,18 and producing behavioral analgesia19 (fig. 1). Therefore, activation of locomotor neurons through this descending pathway permits us to test anesthetic effects on movement independent from nociceptive dorsal horn activation. Fig. 1 Schematic diagram depicting movement pathways from the mesencephalic locomotor region (MLR) and from activation of peripheral nociceptors. In this diagram, + denotes excitatory transmission and − denotes inhibition. Animals were decerebrated ( ... In the current study, we assessed the degree of dorsal versus ventral horn involvement in anesthetic immobilizing action by measuring isoflurane- and halothane-induced depression of movement during locomotion elicited by electrical microstimulation of the MLR. We hypothesized that if the dorsal horn indeed plays little or no role in immobility, anesthetic requirements to block MLR-elicited movement should be approximately equal to those needed to block movement that does rely on nociceptive dorsal horn activation (i.e., MAC determined by supramaximal tail clamp).