The cerebral and systemic effects of movement in response to a noxious stimulus in lightly anesthetized dogs: Possible modulation of cerebral function by muscle afferents

Background: Afferentation theory predicts that agents or maneuvers that stimulate muscle stretch receptors (i.e., muscle afferents) will produce cerebral stimulation. From this theory it follows that, regardless of the source (e.g., drug effect, active muscle movement), increases in stretch receptor activity should result in a similar effect on the brain. The present study tested the hypothesis that active muscle movement in lightly anesthetized subjects would result in cerebral stimulation. Methods: Studies were conducted in six dogs who were lightly anesthetized with halothane (0.70% end-expired). The following physiologic variables were quantified before and for 6 min after the initiation of a standardized (1-min duration) noxious stimulus to the trachea and the skin overlying the hind limb: cerebral blood flow, cerebral metabolic rate for oxygen (CMRO₂), cerebral perfusion pressure, cerebral vascular resistance, electroencephalogram activity, electromyogram activity, arterial carbon dioxide partial pressure (PaCO₂), central venous pressure, and serum epinephrine and norepinephrine concentrations. Response to stimulation was evaluated initially in unparalyzed dogs and later was evaluated in the same dogs after they were paralyzed with intravenous pancuronium (0.2 mg/kg). Results: In unparalyzed dogs, stimulation produced episodes of coughing plus head and limb movement during the 6-min study period. Accompanying the movement was activation of the electromyogram, an increase in electroencephalogram frequency, and a reduction in electroencephalogram amplitude. There also was a 35% increase in cerebral blood flow, a 25% decrease in cerebral vascular resistance, and a 7% increase in CMRO₂ versus the baseline values for each variable. There were no significant increases in either cerebral perfusion pressure, central venous pressure, PaCO₂, or serum norepinephrine concentration to account for the cerebral effects: however, serum epinephrine concentrations increased by 61%. In pancuronium-paralyzed dogs, noxious stimulation resulted in a 5% increase in cerebral blood flow, a 7% decrease in cerebral vascular resistance, and an 5% increase in CMRO₂ versus baseline levels. Electroencephalogram frequency was increased, but amplitude was unchanged. Central venous pressure, electromyogram activity, and serum norepinephrine concentration were unaffected. The serum epinephrine response was similar to that observed when the dogs were not paralyzed. Conclusions: These data support the hypothesis that active muscle movement in lightly anesthetized subjects has an effect on the brain that is mediated in part by muscle afferent receptors. This cerebral response was manifested as electroencephalogram activation, cerebral vasodilation unrelated to central venous pressure changes, and an increase in cerebral blood flow greater than that required to meet metabolic demands. Paralysis with pancuronium abolished movement induced by stimulation (and, thus, the muscle afferent response) and also attenuated the cerebral blood flow, cerebral vascular resistance, and electroencephalogram responses.