Spinal and Supraspinal Mechanisms for Morphine‐Pentobarbital Antinociceptive Interaction in Relation to Cardiac Acceleration Response in Rats

In rat experiments, morphine-pentobarbital antinociceptive interaction affecting cardiac acceleration in response to somatic noxious stimulation was analyzed with the use of intrathecal and intracerebroventricular injections of morphine. Cardiac acceleration response was induced by tail compression, and heart rate was monitored by electrocardiogram. Pentobarbital, in a subanesthetic intravenous dose, antagonized the antinociceptive effect of morphine in relation to cardiac acceleration response when morphine was administered intracerebroventricularly. Without pentobarbital, morphine, 8 μg, almost completely blocked the cardiac acceleration response, which was only 1 ± 1 beats/mm. When pentobarbital (10 mg/kg intravenously) was administered in a combination with the same dose of morphine, the cardiac acceleration response was 29 ± 3 beats/min (P < 0.0001). In contrast, when morphine was administered intrathecally, the antagonism by pentobarbital of the cardiac acceleration response was absent. The results suggest that supraspinal mechanisms play a decisive role in morphine-pentobarbital antagonism in relation to cardiac acceleration response to somatic noxious stimulation.