Neurons in the ventral spinal cord are more depressed by isoflurane, halothane, and propofol than are neurons in the dorsal spinal cord

Abstract

Background: Volatile anesthetics act primarily in the spinal cord to produce immobility but their exact site of action is unclear. Between 0.8 and 1.2 minimum alveolar anesthetic concentration (MAC), isoflurane does not depress neurons in the dorsal horn, suggesting that it acts at a more ventral site within the spinal cord such as in premotor interneurons and motoneurons. We hypothesized that isoflurane, halothane, and propofol would exert a greater depressant effect on nociceptive responses of ventral horn neurons when compared with dorsal horn neurons.

Methods: Rats were anesthetized with isoflurane or halothane and responses of dorsal (<1200 microm deep) and ventral (>1200 microm) lumbar neurons to noxious mechanical stimulation of the hindpaw were determined at 0.8 and 1.2 MAC. In a third group anesthetized with isoflurane at 0.8 MAC, we administered 5 mg/kg propofol while recording responses from dorsal horn or ventral horn neurons.

Results: Dorsal horn neuronal responses were not significantly affected when either isoflurane or halothane was increased from 0.8 to 1.2 MAC; propofol also had no significant effect. On the other hand, with increased isoflurane or halothane concentration, responses of ventral horn neurons were depressed by 60% and 45%, respectively. Propofol profoundly depressed (>90%) ventral horn neurons.

Conclusions: These data suggest that, in the peri-MAC range, isoflurane, halothane, and propofol have little or no effect on neuronal responses to noxious mechanical stimulation in the spinal dorsal horn but depress such responses in the ventral horn. Immobility produced in the 0.8-1.2 MAC range by these anesthetics appears to result from a depressant action in the ventral horn.

Figure 1

Recording sites. (A) Recording sites determined from histologically verified lesions are shown overlaid on a representative drawing of the L4 lumbar spinal cord [taken from the atlas of Paxinos and Watson (15)]. Open circles: sites <1200 μm based on micrometer reading; filled circles: depths >1200 μm. The approximate recording depth can be estimated from the depth marker at right.

Figure 2

Summary data for isoflurane animals. (A) Shown is the total number of action potentials (mean, standard deviation) for the 60-s period after application of the noxious mechanical stimulus at 0.8 and 1.2 minimum alveolar anesthetic concentration (MAC) for dorsal horn neurons (DHNs) and ventral horn neurons (VHNs). (B) Same as (A) but for the evoked response (total number action potentials minus spontaneous activity). *P < 0.05. Note that the VHNs, as compared to the DHNs, are more depressed by the change to 1.2 MAC.

Figure 3

Individual examples of neuronal responses to noxious mechanical stimulation. Shown are action potentials recorded from lumbar neurons in animals anesthetized with isoflurane. Changing the isoflurane concentration from 0.8 to 1.2 minimum alveolar anesthetic concentration (MAC) did not appreciably affect the responses of the dorsal horn neuron (DHN, shown in A); the response at 0.8 MAC was 1472 impulses and was 1339 impulses at 1.2 MAC. Increasing isoflurane from 0.8 to 1.2 MAC decreased the response of a ventral horn neuron (VHN, shown in B) from 829 impulses to 204 impulses (different animal than in A).

Figure 4

Summary data for halothane animals. (A) Shown is the total number of action potentials (mean, standard deviation) for the 60-s period after application of the noxious mechanical stimulus at 0.8 and 1.2 minimum alveolar anesthetic concentration (MAC) for dorsal horn neurons (DHNs) and ventral horn neurons (VHNs). (B) Same as (A) but for the evoked response (total number action potentials minus spontaneous activity). *P < 0.05. Note that the VHNs, as compared to the DHNs, are more depressed by the change to 1.2 MAC.

Figure 5

Summary data for propofol animals. (A) Shown is the total number of action potentials (mean, standard deviation) for the 60-s period after application of the noxious mechanical stimulus for dorsal horn neurons (DHNs, ■) and ventral horn neurons (VHNs, □). Data are from the control period before propofol and the responses 1, 4, 7, 10, and 13 min after propofol (5 mg/kg). (B) Same as (A) but for the evoked response (total number action potentials minus spontaneous activity). *P < 0.05, average of all postpropofol responses compared to control responses. #P < 0.05, 1 min postpropofol response compared with control responses. Note that the VHNs, when compared with the DHNs, are more depressed by the administration of propofol.