PLASMA, BRAIN, AND SPINAL-CORD CONCENTRATIONS OF THIOPENTAL ASSOCIATED WITH HYPERALGESIA IN THE RAT

Background: Although low doses of barbiturates are widely believed to increase sensitivity to pain, studies of the electrophysiologic effect s of these drugs on the neurons involved in nociception in the spinal cord have detected only depressant effects. The goal of the studies re ported here was to quantify the hyperalgesia resulting from low-dose t hiopental infusions and to measure the associated concentrations of th iopental in the plasma, brain, and spinal cord. Methods: Nociception w as measured using the threshold for motor response to pressure stimula tion of the tail (nociceptive threshold) and tail flick latency in the rat. Thiopental was administered by intravenous infusions designed to produce plasma concentrations that either slowly increased or remaine d at a steady state. Plasma and tissue thiopental concentrations were measured by high-performance liquid chromatography. Results: We observ ed a reduction in nociceptive threshold that was correlated with the p lasma thiopental concentration over the range 2-20 mu g.ml(-1) (7.6-76 mu M). The relationship was nonlinear. Nociceptive threshold reached a nadir (36% less than control values) at a mean plasma thiopental con centration of 13.7 mu g.ml(-1) (51.9 mu M). The steady-state study sho wed a similar reduction in nociceptive threshold, with an equilibrium plasma thiopental concentration of 7.6+/-1.3 mu g.ml(-1) (28.8+/-4.9 m u M). Concentrations of thiopental in brain and spinal cord samples we re 1.7+/-0.03 and 3.5+/-1.7 mu g.g(-1), respectively. Conclusions: The se studies confirm previous reports of hyperalgesia in association wit h small doses of thiopental. Reductions in nociceptive threshold and t ail flick latency were observed in association with spinal cord concen trations of thiopental in a range reported by others to depress the el ectrophysiologic activity of neurons involved in nociception.