全身麻醉药激活伤害性离子通道以加重疼痛和炎症。
General anesthetics activate a nociceptive ion channel to enhance pain and inflammation.
作者信息
Matta José A, Cornett Paul M, Miyares Rosa L, Abe Ken, Sahibzada Niaz, Ahern Gerard P
机构信息
Departments of Pharmacology and Physiology and Biophysics, Georgetown University, 3900 Reservoir Road, NW, Washington, DC 20007, USA.
出版信息
Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8784-9. doi: 10.1073/pnas.0711038105. Epub 2008 Jun 23.
General anesthetics (GAs) have transformed surgery through their actions to depress the central nervous system and blunt the perception of surgical insults. Counterintuitively, many of these agents activate peripheral nociceptive neurons. However, the underlying mechanisms and significance of these effects have not been explored. Here, we show that clinical concentrations of noxious i.v. and inhalation GAs excite sensory neurons by selectively activating TRPA1, a key ion channel in the pain pathway. Further, these GAs induce pain-related responses in mice that are abolished in TRPA1-null animals. Significantly, TRPA1-dependent neurogenic inflammation is greater in mice anesthetized with pungent compared with nonpungent anesthetics. Thus, our results show that TRPA1 is essential for sensing noxious GAs. The pronociceptive effects of GAs combined with surgical tissue damage could lead to a paradoxical increase in postoperative pain and inflammation.
全身麻醉药（GAs）通过抑制中枢神经系统和减轻对手术创伤的感知，改变了外科手术。与直觉相反的是，许多这类药物会激活外周伤害性神经元。然而，这些效应的潜在机制和意义尚未得到探索。在这里，我们表明，临床浓度的有害静脉注射和吸入性全身麻醉药通过选择性激活TRPA1（疼痛通路中的关键离子通道）来刺激感觉神经元。此外，这些全身麻醉药在小鼠中诱发与疼痛相关的反应，而在TRPA1基因敲除的动物中这些反应则消失。值得注意的是，与无刺激性麻醉药相比，用刺激性麻醉药麻醉的小鼠中，TRPA1依赖性神经源性炎症更严重。因此，我们的结果表明，TRPA1对于感知有害的全身麻醉药至关重要。全身麻醉药的促痛作用与手术组织损伤相结合，可能导致术后疼痛和炎症出现反常增加。
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