Propofol Produces Immobility via Action in the Ventral Horn of the Spinal Cord by a GABAergic Mechanism

Immobility is an end-point that is produced by all general anesthetics and is predominantly mediated by the spinal cord.1;2 Sonner et al showed that the mechanism by which 2 commonly used anesthetics, propofol and isoflurane, causes immobility is different.3 The immobilizing effects of propofol, which acts at the GABA (gamma amino butyric acid) Type A receptor,4–7 were antagonized in rats by picrotoxin, a noncompetitive GABA antagonist, while picrotoxin had lesser effects on immobility produced by isoflurane.3 Anesthetics might mediate immobility at several anatomical locations within the central nervous system. Previous studies have shown significant depression of the dorsal horn by propofol and isoflurane,8–11 leading to the hypothesis that immobility could be the result of depression at the dorsal horn. In addition, anesthetics depress neurons in the ventral spinal cord, which includes motoneurons and central pattern generators, with the latter group of neurons being particularly sensitive to anesthetics.10;12 Propofol’s sedative effect appears to occur via an action in the tuberomamillary nucleus in the hypothalamus;13 however, it is unclear whether propofol’s immobilizing action occurs there, at another supraspinal site, or in the spinal cord. Therefore, we presently investigated whether the forebrain is critical to propofol-induced immobility by determining propofol requirements in decerebrate rats. We also studied the effects of propofol and isoflurane on spinal neuronal responses to noxious stimulation. These studies were performed in decerebrate rats to exclude any contribution of supraspinal structures and to permit us to obtain control responses in the unanesthetized animal. We were therefore able to determine the full extent of anesthetic effect in the range from no anesthesia to that needed to produce immobility. We hypothesized that isoflurane and propofol would have a similar depressing effect on ventral horn neuronal activity and that the effect of propofol, but not isoflurane, would be significantly reversed by picrotoxin.