A model of intravenous regional anesthesia in rats.

Abstract

We developed an IV regional anesthesia (IVRA) model using the tails of rats to allow preclinical evaluation of the safety and efficacy of drugs used in IVRA and analgesia. Three sequential experiments were designed to determine local anesthetic and analgesic effects of drugs injected IV in the tail. The anesthesia was assessed by monitoring the response of the tail-clamp (RTC) test on the tail, whereas the analgesia was assessed by recording the latency in the tail-flick test on the tail. In the first 2 experiments, we studied the effects of different environmental temperatures (15 degrees C, 25 degrees C, and 37 degrees C) and length of tourniquet time on the tail-flick and tail-clamp tests, respectively. Based on the outcomes of these 2 experiments, the pharmacological effects of 1% lidocaine (L group) and 0.5% bupivacaine (B group) were compared with normal saline (NS group) to evaluate this model in experiment 3. In experiment 1, compared with its baseline, tail-flick latency increased rapidly in the 15 degrees C group (P < 0.0001), whereas there were no changes in tail-flick latency in the 25 degrees C group (P = 0.3640) and the 37 degrees C group (P = 0.0641) after the first 20 minutes of tail submersion in a water bath. RTCs in all rats were positive during the entire observation period. In experiment 2, tail-flick latency did not change compared with baseline tail-flick latency after the first 20 minutes of tourniquet application (P = 0.0902), but significantly increased at the 30-, 40-, 50-, and 60-minute intervals (P = 0.0001). RTCs in all rats were positive during the experiment. In experiment 3, local anesthesia was generated in the tail (distal to the tourniquet) in the L and B groups with a similar onset time of anesthesia (approximately 1 minute), but with a longer recovery time of anesthesia and analgesia in the B group (56.0 +/- 22.0 minutes) than the L group (31.0 +/- 19.0 minutes), whereas no anesthetic and analgesic effects were observed in the NS group. A reliable model for studying IVRA and analgesia has been developed in rats.