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The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is the most common nonopioid analgesic currently used for postoperative pain management. We tested the sustained analgesic effect of ketoprofen emanating from a biodegradable gelatin hydrogel in a rat model of postoperative pain.A sheet of analgesic-infiltrated hydrogel was inserted below the plantaris muscle at the end of surgery. Mechanical thresholds were measured by use of von Frey filaments before and 2 weeks after the operation. The effect of ketoprofen on the postoperative pain was also assessed immunohistochemically by assessing microglial activation in the spinal cord with anti-OX-42 and phosphorylated p38 mitogen-activated protein kinase antibodies.Implantation of ketoprofen-infiltrated gelatin hydrogel exerted a sustained analgesic effect for 1 week after the operation. Preemptive analgesia with zaltoprofen, another NSAID, produced an additive analgesic effect in conjunction with the ketoprofen-infiltrated hydrogel. Microglial activation was attenuated by the treatment with ketoprofen-infiltrated hydrogel on day 3 after the incision.These results demonstrate that ketoprofen was effective in reducing mechanical hypersensitivity for 1 week in a rat model of postoperative pain and that the implantation of NSAID-infiltrated gelatin hydrogel may serve as a useful analgesic method for the long-term relief of patients after surgery.