کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5829843 | 1559007 | 2012 | 7 صفحه PDF | دانلود رایگان |

The present study examined effects of caffeine on antinociception by acetaminophen in the formalin test in mice. It demonstrates that caffeine 10Â mg/kg inhibits antinociception produced by acetaminophen 300Â mg/kg i.p. against phase 2 flinches. Chronic administration of caffeine in the drinking water (0.1, 0.3Â g/l) for 8Â days also inhibits the action of acetaminophen. The selective adenosine A1 receptor antagonist DPCPX 1Â mg/kg i.p. mimics the action of caffeine, but the selective adenosine A2A receptor antagonist SCH58261 3Â mg/kg i.p. does not. While acetaminophen produced the same effect in mice that were +/+, +/â and â/â for adenosine A1 receptors, inhibition of antinociception by caffeine was seen only in +/+ and +/â mice. A higher dose of caffeine, 40Â mg/kg, produced an intrinsic antinociception against formalin-evoked flinches, an effect also seen when caffeine was administered intrathecally. SCH58261 30Â nmol, but not DPCPX 10Â nmol, also produced antinociception when administered intrathecally indicating involvement of adenosine A2A receptors in spinal antinociception. Caffeine reversal of acetaminophen results from actions in the spinal cord, as intrathecal DPCPX 10Â nmol inhibited antinociception by systemic acetaminophen; this was also observed in +/+ but not in â/â adenosine A1 receptor mice. We propose that spinal adenosine A1 receptors contribute to the action of acetaminophen secondarily to involvement of descending serotonin pathways and release of adenosine within the spinal cord. Inhibition of acetaminophen antinociception by doses of caffeine relevant to dietary human intake levels suggests a more detailed consideration of acetaminophen-caffeine interactions in humans is warranted.
Journal: European Journal of Pharmacology - Volume 674, Issues 2â3, 15 January 2012, Pages 248-254