Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat

Abstract

Background: The current study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would increase the duration of antinociception to a thermal stimulus in a dose-dependent fashion in a rat model of sciatic nerve blockade.

Methods: Fifty adult Sprague-Dawley rats (10 rats/group) received unilateral sciatic nerve blocks with 0.2 ml ropivacaine (0.5%) or 0.2 ml ropivacaine (0.5%) plus dexmedetomidine (2.7 microm [0.5 microg/kg], 11.7 microm [2 microg/kg], 34.1 microm [6 microg/kg], or 120.6 microm [20 microg/kg]) in a randomized, blinded fashion. Time to paw withdrawal latency to a thermal stimulus for both paws and an assessment of motor function were measured every 30 min after the nerve block until a return to baseline.

Results: Dexmedetomidine added to ropivacaine increased the duration of dense sensory blockade and time for return to normal sensory function in a dose-dependent fashion (P < 0.005). There was a significant time (P < 0.005), dose (P < 0.005), and time-by-dose effect (P < 0.005) on paw withdrawal latencies of the operative paws. There were no significant differences in paw withdrawal latencies of the control paws, indicating little systemic effect of the dexmedetomidine. The duration of motor blockade was also increased with dexmedetomidine. High-dose dexmedetomidine (120.6 mum) was not neurotoxic.

Conclusion: This is the first study showing that dexmedetomidine added to ropivacaine increases the duration of sensory blockade in a dose-dependent fashion in rats. The findings are an essential first step encouraging future efficacy studies in humans.

Figures

Figure 1

Dexmedetomidine added to ropivacaine enhanced the duration of dense sensory blockade (p

Figure 2A-D

Increasing doses of dexmedetomidine prolonged the duration of paw withdrawal latency to a heat stimulus when compared to the ropivacaine control group. Between group comparisons from 90-210 min found multiple significant differences at individual time points. DEX = dexmedetomidine; PWL = paw withdrawal latency. * indicates statistical significance, p

Figure 3A-F

Between group comparisons from 90-210 min for the dexmedetomidine groups also found multiple significant differences at individual time points. DEX = dexmedetomidine; PWL = paw withdrawal latency. * indicates statistical significance, p

Figure 4A-E

Paw withdrawal latency values of the operative paw (color) versus the unblocked control paw (black) for each drug dose. The analgesic effects of ropivacaine (A) and ropivacaine plus different doses of dexmedetomidine (B-E) were significantly greater in the operative paws. There was little systemic analgesic effect of dexmedetomidine as measured by paw withdrawal latencies of the unblocked control paws. DEX = dexmedetomidine; PWL = paw withdrawal latency.

Figure 5

There was a direct increase in the duration of motor blockade with increasing doses of dexmedetomidine added to ropivacaine for sciatic nerve blockade. A motor block was identified by the observation of a curled paw (motor score = 1). A return to normal paw posture was given a motor score of 0. *All doses containing dexmedetomidine were significantly different from ropivacaine administered alone (p

Figure 6

The highest dose of dexmedetomidine (120.6 μM [20 μg/kg]) studied caused sedative effects immediately following anesthesia that prolonged the time to resumption of righting reflex (RoRR) when compared with all other groups (p