Volatile Anesthetic Effects on Midbrain-elicited Locomotion Suggest that the Locomotor Network in the Ventral Spinal Cord Is the Primary Site for Immobility

Abstract

Volatile anesthetics produce immobility primarily by action in the spinal cord; however, anesthetic effects among different neuronal classes located in different spinal regions, and how they relate to immobility, are not understood. In decerebrated rats, effects of isoflurane and halothane on movement elicited by electrical microstimulation of the mesencephalic locomotor region (MLR) were assessed in relation to minimum alveolar concentration (MAC). Anesthetic effects on step frequency and isometric limb force were measured. The authors also examined effects of MLR stimulation on responses of nociceptive dorsal horn neurons and limb force responses to tail clamp. Mean isoflurane requirements to block MLR-elicited stepping were slightly but significantly greater than MAC by 10%. Mean halothane requirements to block MLR-elicited stepping were greater than those for isoflurane and exceeded MAC by 20%. From 0.4 to 1.3 MAC (but not 0.0 to 0.4 MAC), there was a dose-dependent reduction in the frequency and force of hind limb movements elicited by MLR stimulation during both anesthetics. MLR stimulation inhibited noxious stimulus evoked responses of dorsal horn neurons by approximately 80%. Aptly, MLR stimulation produced analgesia that outlasted the midbrain stimulus by at least 15 s, as indicated by an 81% reduction in hind limb force elicited noxious tail clamp. Because electrical stimulation of the MLR elicits movement independent of dorsal horn activation, the immobilizing properties of isoflurane and halothane are largely independent of action in the dorsal horn. The results suggest that volatile anesthetics produce immobility mainly by action on ventral spinal locomotor networks.