Articles: hyperalgesia.
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Our aim was to determine whether G protein-gated potassium (Kir3) channels contribute to thermonociception and morphine analgesia. Western blotting was used to probe for the presence of Kir3.1, Kir3.2, Kir3.3, and Kir3.4 subunits in the mouse brain and spinal cord. Hot-plate paw-lick latencies for wild-type, Kir3.2 knockout, Kir3.3 knockout, and Kir3.4 knockout mice were measured at 52 degrees C and 55 degrees C, following the s.c. injection of either saline or 10 mg/kg morphine. ⋯ We conclude that G protein-gated potassium channels containing Kir3.2 and/or Kir3.3 play a significant role in responses to moderate thermal stimuli. Furthermore, the activation of Kir3 channels containing the Kir3.2 subunit contributes to the analgesia evoked by a moderate dose of morphine. As such, receptor-independent Kir3 channel agonists may represent a novel and selective class of analgesic agent.
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Anesthesia and analgesia · Dec 2002
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.
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.
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Randomized Controlled Trial Clinical Trial
Mechanisms of postoperative pain: clinical indications for a contribution of central neuronal sensitization.
The relative importance of different nociceptive mechanisms for the intensity, duration, and character of postoperative pain is not well established. It has been suggested that sensitization of dorsal horn neurones may contribute to pain in the postoperative period. We hypothesized that wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia share a common mechanism, sensitization of central neurones, and consequently, that the short-acting opioid remifentanil would have comparable effects on hyperalgesia in both conditions. ⋯ Although remifentanil is not a highly targeted "antihyperalgesic," these results support the hypothesis that both wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia may share common mechanisms, and that central neuronal sensitization may contribute to some aspects of postoperative pain. Antihyperalgesic drugs should be further developed and evaluated in clinical trials of postoperative pain.