Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

Abstract

Rationale: Spinal cord plasticity can be assessed in spinal rats using an instrumental learning paradigm in which subjects learn an instrumental response, hindlimb flexion, to minimize shock exposure. Prior exposure to uncontrollable intermittent stimulation blocks learning in spinal rats but has no effect if given before spinal transection, suggesting that supraspinal systems modulate nociceptive input to the spinal cord, rendering it less susceptible to the detrimental consequences of uncontrollable stimulation.

Objective: The present study examines whether disrupting brain function with pentobarbital blocks descending inhibitory systems that normally modulate nociceptive input, making the spinal cord more sensitive to the adverse effect of uncontrollable intermittent stimulation.

Materials and methods: Male Sprague-Dawley rats received uncontrollable intermittent stimulation during pentobarbital anesthesia after (experiment 1) or before (experiment 2) spinal cord transection. They were then tested for instrumental learning at a later time point. Experiment 3 examined whether these manipulations affected nociceptive (thermal) thresholds.

Results: Experiment 1 showed that pentobarbital had no effect on the induction of the learning deficit after spinal cord transection. Experiment 2 showed that intact rats anesthetized during uncontrollable intermittent stimulation failed to learn when later transected and tested for instrumental learning. Experiment 3 found that uncontrollable intermittent stimulation induced an antinociception in intact subjects that was blocked by pentobarbital.

Conclusions: The results suggest a surgical dose of pentobarbital (50 mg/kg) suppresses supraspinal (experiment 2) but not spinal (experiment 1) systems that modulate nociceptive input to the spinal cord by blocking the antinociception that is induced by this input (experiment 3).

Fig. 1

Effect of pentobarbital on mean response duration (a, b) and response number (c, d) in animals exposed to uncontrollable intermittent stimulation (shocked) or tube restraint (unshocked) after spinal cord transection. Subpanels a and c depict the data over the 30-min test period. Each point represents the average observed over a 60-s time bin. The right panels (b, d) represent mean performance collapsed across time (±SEM; n=6)

Fig. 2

Impact of pentobarbital on mean response duration (a, b) and response number (c, d) in rats given uncontrollable intermittent stimulation (shocked) or restraint (unshocked) before spinal cord transection. Subpanels a and c depict the data over the 30-min test period. Each point represents the average observed over a 60-s time bin. The right panels (b, d) represent mean performance collapsed across time (±SEM; n=6)

Fig. 3

Impact of pentobarbital treatment on tail withdrawal from radiant heat in anesthetized (Pento) and awake (Saline) rats given uncontrollable intermittent stimulation (shocked) or nothing (unshocked). The error bars indicate the SEM (n=6)