Effect of morphine on the heart rate response to noxious stimulation: interaction with halothane and naloxone.

The effect of morphine on the heart rate increase, in response to noxious somatic stimulation, was studied in 125 rat experiments. It was found that halothane, in a subanesthetic concentration of 0.3 vol%, profoundly weakened the effect of morphine on the heart rate response. As a result, the morphine ED50 value for blockade of the heart rate response was increased from 5.9 to 46.1 mg/kg (P less than 0.001). Naloxone in a dose of 0.05 mg/kg increased the morphine ED50 value for blockade of the heart rate response 11-fold (morphine was administered without halothane). However, the same dose of naloxone did not change the morphine ED50 value obtained with combined administration of morphine and halothane. An increase in the naloxone dosage (up to 1 mg/kg) was necessary to demonstrate the naloxone antagonistic effect (8-fold increase in the morphine ED50 value) when morphine was given with halothane. It has been suggested that the effect of morphine on the heart rate response to noxious stimulation results primarily from the activation of inhibitory control mechanisms concerned with this response (indirect effect). Halothane depresses the inhibitory control mechanisms and, therefore, weakens the effect of morphine. A significant increase in doses of morphine is needed to provide the direct antinociceptive effect.