The effects of intrathecal administration of an antagonist for prostaglandin E receptor subtype EP(1) on mechanical and thermal hyperalgesia in a rat model of postoperative pain.

Abstract

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 E(2) 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 E(2) receptor subtype EP(1), 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 micro g) 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 EP(1) receptor-mediated sensitization of the spinal dorsal horn may contribute to the generation of mechanical, but not thermal, hyperalgesia and that an EP(1) receptor antagonist administered intrathecally is a potential analgesic for postoperative pain, especially mechanically evoked pain (incident pain). We examined the effects of an intrathecally administered selective EP(1) receptor antagonist on mechanical and thermal hyperalgesia in a postoperative pain model. The intrathecal EP(1) receptor antagonist inhibited the mechanical, but not thermal, hyperalgesia, indicating the potential for an EP(1) receptor antagonist to be used as an analgesic for postoperative pain, especially incident pain.