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The purpose of this prospective, double-blind, randomized study was to evaluate pain reduction using an intraosseous injection of slow-releasing methylprednisolone in teeth with irreversible pulpitis. Forty subjects presenting for emergency treatment completed the study. Each subject had a tooth with a clinical diagnosis of irreversible pulpitis with actively associated moderate to severe pain. After local anesthesia was attained, the subjects were randomly assigned to receive an intraosseous injection of either 1.0 ml of Depo-Medrol (40 mg) or 1.0 ml of sterile saline (control). No endodontic therapy was begun at the initial appointment. The subjects received ibuprofen and Tylenol #3 and completed a 7-day questionnaire on pain, percussion pain, and analgesic medications taken each day. Over the 7-day observation period, the subjects who received the intraosseous injection of Depo-Medrol reported significantly (p < 0.05) less pain and percussion pain while taking significantly (p < 0.05) fewer pain medications. Clinically the intraosseous injection of Depo-Medrol could be used to temporarily alleviate the symptoms of irreversible pulpitis until definitive treatment can be rendered.