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Effect of morphine on the heart rate response to noxious stimulation: interaction with halothane and naloxone
Igor Kissin1, Reid C Kerr, Richard L Smith
1Department of Anesthesiology, School of Medicine, University of Alabama in Birmingham, University Station, Birmingham, AL 35294 U.S.A.
Abstract:
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.
Insights
This study found that halothane significantly weakens morphine's pain-blocking effects in rats by inhibiting natural pain control mechanisms. Higher morphine doses are needed when combined with halothane for pain relief.
Area of Science:
- Anesthesiology
- Pharmacology
- Neuroscience
Background:
- Morphine is a potent analgesic, but its efficacy can be influenced by other anesthetic agents.
- Understanding drug interactions is crucial for optimizing pain management and anesthesia protocols.
Purpose of the Study:
- To investigate the effect of subanesthetic halothane on morphine's ability to block heart rate responses to noxious stimulation in rats.
- To determine the interaction between halothane, morphine, and naloxone in modulating antinociception.
Main Methods:
- 125 rat experiments were conducted to assess heart rate responses to noxious somatic stimulation.
- Morphine's efficacy was evaluated with and without subanesthetic halothane (0.3 vol%).
- Naloxone was administered at varying doses to assess its antagonistic effect in the presence and absence of halothane.
Main Results:
- Subanesthetic halothane significantly increased the morphine ED50 for blocking heart rate response (from 5.9 to 46.1 mg/kg).
- Low-dose naloxone (0.05 mg/kg) showed an 11-fold increase in morphine ED50 without halothane, but no significant change with halothane.
- Higher naloxone doses (up to 1 mg/kg) were required to demonstrate antagonism when halothane was co-administered.
Conclusions:
- Halothane weakens morphine's antinociceptive effect, likely by depressing inhibitory control mechanisms involved in the heart rate response.
- The interaction suggests morphine's primary effect is indirect, mediated through inhibitory pathways that halothane impairs.
- Higher morphine doses are necessary for direct antinociceptive effects when halothane is present.