Alterations by captopril of pain reactions due to thermal stimulation of the mouse foot: Interactions with morphine, naloxone and aprotinin

Abstract

The effects of Captopril (SQ 14,225) were studied in mice both by measuring the reaction time and observing the number of jumping mice in the ‘hot-plate’ test. Subcutaneous injections of captopril (0.1-0.4 mg/kg) produced a significant increase in the reaction time at the 4th hour after the injection while no difference in the reaction time was observed at other times. Captopril caused a clear-cut increase in the number of jumping mice which was found to be greater with lower doses of the compound. Morphine alone did not cause an increase in the number of jumping mice, but increased the reaction time which reached a maximum 1 h after administration and gradually returned to the control level after 6 h. Injection of morphine to the captopril-pretreated mice caused a highly significant increase in reaction time remaining above the control values for 3 h. This effect of morphine was antagonized by naloxone (2 mg/kg, s.c.). Captopril, when given together with morphine, prevented the increase in reaction time over 2 h, but caused a progressive and significant increase within 6 h. Morphine also prevented the jumping behaviour induced by captopril. Aprotinin (50 000 KIU/kg i.p.) when given together with captopril, produced a significant increase in reaction time but almost completely blocked the jumping reaction. Aprotinin also prevented the captopril-induced increase in the number of jumping mice. The possible mechanisms of analgesia and jumping behaviour due to thermal stimulation are discussed in the light of these findings.