General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1
General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1
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DOI：
10.1124/mol.108.049684
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Ahern, Gerard P.
中科院分区：
文献类型：
--
作者：
Cornett, Paul M.;Matta, Jose A.;Ahern, Gerard P.
全身麻醉药（GA）是中枢神经系统抑制剂，使患者对外界刺激无反应。相比之下，这些药物中的许多也已知刺激外周感觉神经，增加了它们可能加剧组织炎症的可能性。我们已经发现刺激性GAs通过直接激活瞬时受体电位（TRP）A1离子通道来兴奋感觉神经元。在这里，我们表明，气体也敏感辣椒素受体TRPV1，一个关键的离子通道表达在伤害性神经元。临床相关浓度的异氟烷、七氟烷、恩氟烷和地氟烷使TRPV 1对辣椒素和质子敏感，并降低热激活阈值。此外，异氟烷在刺激蛋白激酶C后直接激活TRPV 1。同样，在同时应用缓激肽（组织损伤期间形成的关键炎症介质）期间，异氟烷兴奋TRPV1和感觉神经元。因此，GA可以增强手术诱导的组织损伤期间发生的TRPV1的激活。这些结果支持了这样的假设，即一些GAs，通过直接作用于TRP通道，增加术后疼痛和炎症。
General anesthetics (GAs) are central nervous system depressants that render patients unresponsive to external stimuli. In contrast, many of these agents are also known to stimulate peripheral sensory nerves, raising the possibility that they may exacerbate tissue inflammation. We have found that pungent GAs excite sensory neurons by directly activating the transient receptor potential (TRP) A1 ion channel. Here, we show that GAs also sensitize the capsaicin receptor TRPV1, a key ion channel expressed in nociceptive neurons. Clinically relevant concentrations of isoflurane, sevoflurane, enflurane, and desflurane sensitize TRPV1 to capsaicin and protons and reduce the threshold for heat activation. Furthermore, isoflurane directly activates TRPV1 after stimulation of protein kinase C. Likewise, isoflurane excites TRPV1 and sensory neurons during concomitant application of bradykinin, a key inflammatory mediator formed during tissue injury. Thus, GAs can enhance the activation of TRPV1 that occurs during surgically induced tissue damage. These results support the hypothesis that some GAs, through direct actions at TRP channels, increase postsurgical pain and inflammation.