Crawley Brianna, Saito Osamu, Malkmus Shelle, Fitzsimmons Bethany, Hua Xiao-Ying, Yaksh Tony L
Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Neurosci Lett. 2008 Sep 5;442(1):50-3. doi: 10.1016/j.neulet.2008.06.062. Epub 2008 Jun 27.
Acetaminophen is an analgesic and antipyretic drug believed to exert its effect through interruption of nociceptive processing. In order to determine whether this effect is due to peripheral or central activity, we studied the efficacy of systemic (oral) and intrathecal (IT) application of acetaminophen in preventing the development of hyperalgesia induced through the direct activation of pro-algogenic spinal receptors. Spinal administration of substance P (SP, 30 nmol, IT) in rats produced a decreased thermal threshold, indicating centrally mediated hyperalgesia. Pretreatment of rats with oral acetaminophen (300 mg/kg), but not vehicle, significantly attenuated IT SP-induced hyperalgesia. Acetaminophen given IT also produced a dose-dependent (10-200 microg) antinociceptive effect. In addition, oral acetaminophen suppressed spinal PGE(2) release evoked by IT SP in an in vivo IT dialysis model. The ability of IT as well as oral acetaminophen to reverse this spinally initiated hyperalgesia emphasizes the likely central action and bioavailability of the systemically delivered drug. Jointly, these data argue for an important central antihyperalgesic action of acetaminophen.
对乙酰氨基酚是一种镇痛和解热药物，据信其通过中断伤害性感受过程发挥作用。为了确定这种作用是由于外周还是中枢活性，我们研究了对乙酰氨基酚全身（口服）和鞘内（IT）给药在预防通过直接激活促痛性脊髓受体诱导的痛觉过敏发展中的疗效。在大鼠中鞘内注射P物质（SP，30 nmol，IT）导致热阈值降低，表明存在中枢介导的痛觉过敏。用口服对乙酰氨基酚（300 mg/kg）而非赋形剂预处理大鼠，可显著减轻IT SP诱导的痛觉过敏。鞘内给予对乙酰氨基酚也产生剂量依赖性（10 - 200 μg）的镇痛作用。此外，在体内IT透析模型中，口服对乙酰氨基酚抑制了IT SP引起的脊髓PGE₂释放。鞘内以及口服对乙酰氨基酚逆转这种脊髓引发的痛觉过敏的能力强调了全身给药药物可能的中枢作用和生物利用度。综合这些数据表明对乙酰氨基酚具有重要的中枢抗痛觉过敏作用。
