The Role of the Spinal Opioid Receptor Like1 Receptor, the NK-1 Receptor, and Cyclooxygenase-2 in Maintaining Postoperative Pain in the Rat

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Abstract
1 receptor, the opioid receptor like1 (ORL1) receptor, and cyclooxygenase (COX)-2 reportedly are involved in the development of spinal sensitization. In this study, we clarified the role of the NK-1 receptor, the ORL1 receptor, and COX-2 in the maintenance of mechanical hyperalgesia induced by skin incision. A 1-cm longitudinal incision was made through skin and fascia of the plantar aspect of the right foot in the rat. Four hours after the skin incision, significant mechanical hyperalgesia developed. An ORL1 receptor agonist (nociceptin), NK-1 receptor antagonists (CP-96,345 and FK888), and COX-2 inhibitors (NS398 and JTE522) were administered intrathecally 4 h after the skin incision. An ORL1 receptor agonist and NK-1 receptor antagonists, but not COX-2 inhibitors, significantly attenuated the level of mechanical hyperalgesia induced by the skin incision. These findings suggest that the spinal ORL1 receptor and the NK-1 receptor play an important role in maintaining the mechanical hyperalgesia induced by skin incision. Implications Intrathecal injection of an NK-1 receptor antagonist and an ORL1 receptor agonist may be effective for the treatment of postoperative incident pain....