Influence of timing of administration on the analgesic effect of bupivacaine infiltration in carrageenin-injected rats

Recent evidence has suggested that the timing of administration of analgesic drugs could influence their efficacy by reducing the sensitization of the nervous system induced by the nociceptive inputs, but this concept of preemptive analgesia is still debated in both clinical and basic research. The model of acute inflammatory pain induced by carrageenin was used to study the influence of timing of administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005 mg/ml epinephrine) on the development of hyperalgesia, edema, and increase in temperature. The animals received bupivacaine 5 min before (BUPI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrageenin (1 ml/kg of 1% solution) was injected into the left hind paw. Two control groups (n = 15 in each) received saline 5 min before or 60 min after administration of carrageenin. Hyperalgesia of the injected paw was evaluated by the vocalization threshold to paw pressure, edema by measuring paw circumference with a thread, and plantar temperature with a thermocouple thermometer. All measurements were done before carrageenin injection then every 30 min thereafter for 240 min. Another series (n = 24), with the same four groups was also evaluated at 24 h. Local injection of bupivacaine 60 min after carrageenin partially reduced the edema and hyperalgesia. The injection of bupivacaine 5 min before carrageenin was more efficient than the delayed injection and reduced hyperalgesia, edema and the increase in temperature temporarily, but did not totally prevent their development. All groups were similar at 240 min and 24 h. These results show that a slight advantage of infiltration with bupivacaine before injury exists in this carrageenin model of acute inflammatory pain. However, this benefit is limited in time and bupivacaine did not have any preemptive analgesic effect.