Effect of Systemic and Intrathecal Morphine in a Rat Model of Postoperative Pain

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Abstract
Background: To learn more about persistent pain after an incision, a rat model for postoperative pain has been developed. To further evaluate this model, the authors examined the effect of intrathecal (IT) and subcutaneous (SC) morphine, effective for postoperative pain relief in patients, on pain behaviors immediately after surgery and 1 day after surgery. Methods: Rats were anesthetized with halothane, and a 1-cm incision was made in the plantar aspect of the foot and closed. After recovery, the rats were placed on an elevated plastic mesh floor, and withdrawal threshold was determined using calibrated von Frey filaments (15-522 mN) applied from beneath the test cage to an area adjacent to the wound at the heel. Pain behaviors also were assessed using the response frequency to a nonpunctate mechanical stimulus and a cumulative pain score. Results: Mechanical hyperalgesia and nonevoked pain behaviors were present on the day of surgery and 1 day after surgery. Administration of either SC (0.3-3.0 mg/kg) or IT (0.16-5.0 micrograms) morphine reversibly increased the withdrawal threshold. The response frequency to the nonpunctate stimulus and the nonevoked pain scores also were decreased by 3 mg/kg of SC or 5 micrograms of IT morphine. Naloxone (1 mg/kg) reversed morphine-produced hypoalgesia. Conclusion: This is the first study to demonstrate that mechanical hyperalgesia to a nonpunctate stimulus occurs after a surgical incision in the rat. This rat model of postoperative has several similarities to postoperative patients: mechanical hyperalgesia to punctate and nonpunctate stimuli, nonevoked pain, and pain behaviors inhibited by SC and IT morphine. This model also may be useful for predicting analgesia by investigational agents for postoperative pain.