Liu L, Zhu W, Zhang Z-S, Yang T, Grant A, Oxford G, Simon S A
Department of Anesthesiology, Duke University, Durham 27710, USA.
J Neurophysiol. 2004 Apr;91(4):1482-91. doi: 10.1152/jn.00922.2003. Epub 2003 Dec 3.
Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (approximately 41 degrees C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.
尼古丁是一种被大量人群使用的生物碱。进入人体后，它会产生大量主要通过激活神经元烟碱型乙酰胆碱受体（nAChRs）而发生的生理作用。我们研究了其调节瞬时受体电位香草酸亚型1（TRPV1）受体和电压门控钠通道的能力。研究尼古丁对钠通道作用的原因是为了更好地理解其抗伤害感受特性。研究其对辣椒素激活的TRPV1通道作用的原因是为了了解它如何调节这个涉及疼痛、炎症和味觉生理的通道。来自大鼠三叉神经节（TG）伤害感受器的全细胞膜片钳记录显示，尼古丁通过减少诱发动作电位的数量和抑制河豚毒素抗性钠电流而表现出麻醉特性。这种麻醉特性无需激活nAChRs即可产生。尼古丁还调节TRPV1受体，在TG神经元和异源表达TRPV1受体的细胞中，使辣椒素激活的电流增加数倍。这种敏化作用不需要激活nAChRs。尼古丁并未改变TG神经元中归因于TRPV1受体激活的热激活电流的阈值温度（约41摄氏度）。在这方面，它对TRPV1受体的作用不同于乙醇，乙醇已被证明会增加辣椒素激活的电流，但会降低阈值温度。这些研究记录了尼古丁对涉及伤害感受的通道的几种新作用，并表明它们可能如何影响涉及疼痛和味觉的生理过程。
