Can determining the minimum alveolar anesthetic concentration of volatile anesthetic be used as an objective tool to assess antinociception in animals?
We intended to evaluate the reliability of the minimum anesthetic alveolar concentration (MAC)-sparing effect as an objective measure of the antinociceptive properties of a drug. For this purpose, we tested different variables and analyzed the significance of the results obtained. In a first set of experiments, we studied rats under mechanical ventilation and sevoflurane anesthesia. Outcome variables such as gross purposeful movements consecutive to tail clamping, paw withdrawal consecutive to increasing pressure, and cardio-circulatory reactivity (MACBAR) after these stimuli were recorded. In a second set of experiment, sevoflurane-anesthetized rats under spontaneous breathing conditions were used. Thermal stimuli were compared with pressure. The MAC-sparing effect of several doses of sufentanil and clonidine was evaluated in both anesthetized and awake rodents. When considering the stimulus applied, larger concentrations of sevoflurane were required to suppress reactivity after tail clamp than after paw pressure or radiant heat (1.81 +/- 0.28 versus 1.45 +/- 0.22 and 1.53 +/- 0.26; P < 0.05). For the two first stimuli, no significant differences were noted between the concentrations that suppress motor or cardio-circulatory reactions. All doses of sufentanil tested significantly reduced (P < 0.05) the different MAC values except the smallest one (0.005 micro g x kg(-1) x min(-1)) that significantly increased MACBAR in ventilated animals and both MAC and MACBAR in spontaneously breathing rodents (P < 0.05). Clonidine, at its optimal dose (10 micro g/kg), significantly reduced both MAC and MACBAR to the same degree. In awake animals submitted to radiant heat or pressure challenge, none of the clonidine doses nor sufentanil doses (0.005 and 0.07) were active. In conclusion, the MAC-sparing effect provides several reliable and quantifiable variables that allow comparison between different analgesic substances. However, the observations made are not simply the result of antinociceptive effects of the tested drugs but rather that of complex interactions between these drugs and a halogenated vapor.


CONCLUSIONS
The MAC-sparing effect provides several variables that allow comparison between different analgesic substances. However, the observations made are not simply the result of the antinociceptive effects of the tested drugs but rather the result of complex interactions between these drugs and a halogenated vapor.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000097:blood / Q000494:pharmacology; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D009068:Movement / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects*; D011312:Pressure; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects; D015203:Reproducibility of Results; D012121:Respiration, Artificial; D017409:Sufentanil / Q000097:blood / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D017450:Receptors, Opioid, mu; D017409:Sufentanil; D003000:Clonidine