Pre-emptive analgesia in rats with artificial ureteric calculosis: Effects on visceral pain behavior in the post-operative period

Abstract

‘Pre-emptive’ analgesia is a controversial issue in both the clinical and experimental literature on pain. This paper investigates the effect of chronic (4 days) administration of morphine or ketoprofen initiated pre- or post-operatively on behavioral indicators of visceral pain and referred hyperalgesia in an animal model of artificial ureteric calculosis. In the morphine experiment, female Sprague–Dawley rats were treated i.p. with saline or morphine sulphate (2.5 or 5 mg/kg/day) starting either 45 min before or 45 min after surgery (pentobarbital anesthesia) for stone implantation in the left ureter, until the 4th day after intervention. Behavioral crises of ureteric pain were recorded (video-tape) in all rats over 4 days post-operatively. Number, duration and complexity of crises of stone-rats were significantly and dose-dependently reduced by administration of morphine with respect to saline in an identical manner for the pre- and post-operative treatment. In the ketoprofen experiment, rats were given saline or ketoprofen (15 mg/kg/day, in 3 i.p. injections per day) starting either pre- or post-operatively with the same paradigm as for the morphine study. Vocalization thresholds to electrical stimulation of the left oblique musculature were measured daily for 3 days pre- and 4 days post-operatively. Muscle hyperalgesia (post-operative decrease in threshold with respect to pre-stone implantation) was significantly reduced in extent and duration in ketoprofen with respect to saline-injected animals but no difference was found between the pre- and post-operative treatment. It is concluded that pre-emptive administration of morphine or ketoprofen has no advantage in reducing behavioral indicators of visceral pain and referred hyperalgesia in this animal model.