The excitatory and inhibitory effects of nitrous oxide on spinal neuronal responses to noxious stimulation

Because of the logistical obstacles to measurement under hyperbaric conditions, the effect of nitrous oxide (N2O) alone on spinal neuronal responses has not been tested. We hypothesized that, like other inhaled anesthetics, N2O would depress spinal neuronal responses to noxious stimulation.

The lumbar spinal cord was exposed in rats anesthetized with isoflurane. Mechanically ventilated rats were placed into a hyperbaric chamber and needle electrodes were inserted into the hindpaws. Isoflurane administration was discontinued and anesthesia converted to N2O by pressurizing the chamber with N2O. A microelectrode was inserted into the lumbar cord using computer-controlled motors and a hydraulic microdrive. Neuronal responses to electrical stimulation of the hindpaw were sought at 1.5, 2, and 2.5 atm N2O (0.8-1.3 minimum alveolar concentration).

Increasing N2O partial pressures variably affected neuronal responses to a 2 s 100-Hz electrical stimulus. Neuronal depth and neuronal response were correlated, with superficial neurons tending to be facilitated, while deeper neurons were depressed; (overall responses were 1331 +/- 408, 1594 +/- 383, and 1578 +/- 500 impulses/min at 1.5, 2, and 2.5 atm N2O, respectively; mean, standard error). N2O did not affect neuronal responses to a repetitive "windup" stimulus. Infusion of the N-methyl-d-aspartate blocker MK-801 into separate rats increased the neuronal response to the 100-Hz stimulus (from 781 +/- 216 to 1352 +/- 269 impulses/min, P < 0.05).

N2O facilitated superficial spinal neuronal responses to noxious stimulation while depressing deeper neurons. These results suggest that anesthetic partial pressures of N2O have divergent effects on spinal neuronal responses to noxious stimulation, the specific responses depending on the depth of the spinal neurons.