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Wiley InterScience | |
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KEYWORDS analgesia • anti-emetic • dopamine D2 receptor antagonist • 5-HT3 receptor antagonist • hyperalgesia • ondansetron
- 1.
Opioid analgesics and anti-emetics are often used concomitantly to treat pain and nausea and vomiting in people with malignant disease. We investigated interactions between the opioid analgesic morphine and the anti-emetic metoclopramide, a dopamine D2 receptor antagonist, on nociception and gross motor function. - 2.
To assess for antinociceptive interactions, 11 Sprague-Dawley rats were injected intraperitoneally with morphine (5.0 mg/kg) or saline in combination with metoclopramide (0.5, 1.5 and 5.0 mg/kg) or saline and, 30 min later, the tail-flick latencies to a noxious thermal stimulus (49°C water) were measured. Immediately thereafter we induced reperfusion hyperalgesia in the rats' tails using a tourniquet cuff and tested nociception again. Because, in addition to its ability to block D2 receptors, metoclopramide is also a weak 5-HT3 receptor antagonist, we assessed in a further 11 rats whether any antinociceptive interactions occurred between morphine (5.0 mg/kg) and ondansetron (0.2 and 2.0 mg/kg), an anti-emetic that selectively antagonizes 5-HT3 receptors. To assess for motor interactions, we injected another group of nine rats with morphine (5.0 mg/kg) or saline in combination with metoclopramide (0.5 and 5.0 mg/kg) or saline and tested the ability of the animals to run on an 80 mm diameter rod rotating at 25 r.p.m. for 30 min. - 3.
Metoclopramide was not inherently analgesic or antihyperalgesic, but the highest dose of metoclopramide (5.0 mg/kg) enhanced the analgesic and antihyperalgesic effects of morphine. Neither dose of ondansetron was analgesic or antihyperalgesic or enhanced the antinociceptive actions of morphine. - 4.
Only the high dose of metoclopramide compromised running performance when administered with saline. However, coadministering morphine with metoclopramide (both doses) decreased motor performance. - 5.
Therefore, metoclopramide, possibly through its actions on D2 receptors and not 5-HT3 receptors, enhances the analgesic and antihyperalgesic effects of morphine, but morphine exacerbates metoclopramide-induced motor dysfunction in rats.
Received 7 February 2006; revision 21 June 2006; accepted 25 June 2006. DIGITAL OBJECT IDENTIFIER (DOI) 10.1111/j.1440-1681.2007.04533.x About DOI
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