This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Omote, K. Articles by Namiki, A. Search for Related Content PubMed PubMed Citation Articles by Omote, K. Articles by Namiki, A. Related Collections Regional Anesthesia Pain Pharmacology

---

PAIN MEDICINE

The Effects of Intrathecal Administration of an Antagonist for Prostaglandin E Receptor Subtype EP₁ on Mechanical and Thermal Hyperalgesia in a Rat Model of Postoperative Pain

Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan

Address correspondence and reprint requests to Keiichi Omote, MD, Associate Professor, Department of Anesthesiology, Sapporo Medical University School of Medicine, South-1, West-16, Chuoke, Sapporo 060-8543, Japan. Address e-mail to komote{at}sapmed.ac.jp

Despite substantial advances in understanding acute pain mechanisms and in the treatment of pain, postoperative pain, especially mechanically evoked pain (incident pain), is generally not effectively treated. Tissue injury and inflammation increase the release of prostaglandin E₂ in the spinal cord, contributing to the development of hyperalgesia. We designed the present study to determine whether the intrathecal administration of an antagonist for prostaglandin E₂ receptor subtype EP₁, ONO-8711, has an analgesic effect on incision-induced mechanical and thermal hyperalgesia. A 1-cm longitudinal skin incision was made in the plantar aspect of the rat foot. The withdrawal threshold to mechanical stimulation and the withdrawal latency to thermal stimulation applied adjacent to the wound of the hindpaw were investigated. Both mechanical and thermal hyperalgesia were observed at 2 h and 24 h after the incision had been made. ONO-8711 (50, 80, 100 µg) or saline was administered intrathecally. ONO-8711 significantly increased the withdrawal thresholds to mechanical stimulation, but not to thermal stimulation, in a dose- and time-dependent manner. We conclude that EP₁ receptor-mediated sensitization of the spinal dorsal horn may contribute to the generation of mechanical, but not thermal, hyperalgesia and that an EP₁ receptor antagonist administered intrathecally is a potential analgesic for postoperative pain, especially mechanically evoked pain (incident pain).

IMPLICATIONS: We examined the effects of an intrathecally administered selective EP₁ receptor antagonist on mechanical and thermal hyperalgesia in a postoperative pain model. The intrathecal EP₁ receptor antagonist inhibited the mechanical, but not thermal, hyperalgesia, indicating the potential for an EP₁ receptor antagonist to be used as an analgesic for postoperative pain, especially incident pain.

This article has been cited by other articles:

				C.-R. Lin, F. Amaya, L. Barrett, H. Wang, J. Takada, T. A. Samad, and C. J. Woolf Prostaglandin E2 Receptor EP4 Contributes to Inflammatory Pain Hypersensitivity J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1096 - 1103. [Abstract] [Full Text] [PDF]