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The present study was designed to test the hypothesis that perineural dexmedetomidine provides a longer duration of analgesia than the same dose given subcutaneously in a peripheral nerve block in rats.Fifty-four rats received unilateral sciatic nerve blocks along with a subcutaneous injection at the base of the neck by a blinded investigator assigned at random. Combinations were as follows: perineural ropivacaine alone and subcutaneous (SQ) saline, perineural ropivacaine plus dexmedetomidine and SQ saline, perineural ropivacaine and SQ dexmedetomidine, perineural dexmedetomidine alone and SQ saline, and perineural saline and SQ dexmedetomidine. The ropivacaine concentration was fixed at 0.5%, and the dose of dexmedetomidine was 20.0 μg/kg (119.3 μmol/L). Sensory analgesia was assessed by paw withdrawal latency (PWL) to a thermal stimulus every 30 mins after the block for a minimum of 240 mins or until the return of normal sensory function. The unblocked paw served as the control for assessment of systemic, centrally mediated analgesia. Between-group and within-group comparisons of PWL were obtained for measures from operative and control paws.The analgesic effect of perineural dexmedetomidine was superior to that of subcutaneous dexmedetomidine in ropivacaine sciatic nerve blocks from time points 120 to 210 mins (P < 0.017). Perineural dexmedetomidine also showed less systemic effect as measured by the unblocked control paw at multiple time points (P < 0.05). Perineural dexmedetomidine alone provided a brief, partial sensory block.Sensory analgesia provided by dexmedetomidine added to ropivacaine for peripheral nerve blocks in rat is a peripherally mediated effect.