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Unlabelled: Butamben, a lipophilic local anesthetic of the ester class, produces a differential nerve block of long duration. Epidural and peripheral nerve blocks with butamben, formulated as a 5%--10% suspension, result in prolonged analgesia without significant motor blockade. We evaluated the effect of butamben sciatic nerve block on antinociception using the rat paw formalin test, as well as withdrawal latencies to thermal stimulation, and assessed histologic changes in the nerve. After right sciatic nerve block with butamben 5% or saline, responses to intradermal injection of 5% formalin were recorded in randomly selected groups of 6 animals each on days 1, 2, 5, 10, 21, and 28. In an additional group of 8 thermal challenges to both hind paws were recorded at 1, 2, 5, 7, 10, 14, 17, 21, and 28 days after right sciatic butamben 5% blocks. Butamben injection decreased the formalin-induced flinches on days 2, 5, 10, 21 and 28 and decreased thermal challenges on days 1 through 17. Histologic changes were minimal. This study demonstrates a prolonged antinociceptive effect from butamben nerve block to both formalin-induced nociception and heat hyperalgesia, without an effect on gross motor function or histologic morphology., Implications: Butamben 5% nerve blocks produced a prolonged antinociceptive effect to formalin-induced nociception and heat hyperalgesia, without significant motor effect or evidence of substantial histologic changes.