美国科学家近日研究发现，辣椒中的辣椒素（Capsaicin）可帮助某些麻醉剂进入细胞。这一研究将有助于开发新的治疗手段——缓解疼痛而不会导致麻痹和暂时性的瘫痪。相关论文发表在10月4日的《自然》上。
目前，许多局部麻醉剂的工作原理是阻碍钠离子通道以缓解疼痛。但是，这一方法存在很多副作用。它会关闭传输触觉信息及控制运动信息的神经活动，这就是为什么很多人在进行口腔局部麻醉后，出现流口水、胡言乱语以及舌头麻木等状况的原因。
在最新的研究中，美国哈佛医学院的神经学家Bruce Bean发现，辣椒素能够开启痛觉神经上的TRPV-1通道，并且该通道异常宽大，看起来似乎能让麻醉剂从中通过。Bean和同事紧接着在小鼠身上进行了实验，他们首先向小鼠坐骨神经附近单独注射了局部麻醉剂QX-314（它的作用机制也是阻碍钠离子通道），小鼠一如所料表现出正常的疼痛反应；接下来他们在注射QX-314之后又注射了辣椒素，这样TRPV-1通道被打开，小鼠的疼痛感觉消失，这种止痛效应持续了90分钟。而且，注射辣椒素不会像注射传统局部麻醉剂利多卡因（lidocaine）那样会损害小鼠后肢的活动能力。
Bean表示，这种方法将来可能有助于医生选择性地减少疼痛，而不会导致麻痹或妨碍运动。他说：“首先跃入我脑海的例子就是分娩。”
美国加州大学旧金山分校的神经生理学家David Julius表示，这一观点虽然简单却很精致。不过他提醒说，目前还不能保证该方法能很好地在人身上应用。其中一个问题就是，注射QX-314能否完全抵消辣椒素带来的火烧火燎的痛觉。针对这一问题，Bean表示，他已计划研究其它类似药物，以发现比QX-314效率更高的替代品。（科学网 梅进/编译）
原始出处:
Nature 449, 607-610 (4 October 2007) | doi:10.1038/nature06191; Received 21 June 2007; Accepted 28 August 2007
Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers
Alexander M. Binshtok1, Bruce P. Bean2 & Clifford J. Woolf1
Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
Correspondence to: Bruce P. Bean2 Correspondence and requests for materials should be addressed to B.P.B. (Email: bruce_bean@hms.harvard.edu).
Most local anaesthetics used clinically are relatively hydrophobic molecules that gain access to their blocking site on the sodium channel by diffusing into or through the cell membrane1. These anaesthetics block sodium channels and thereby the excitability of all neurons, not just sensory neurons. We tested the possibility of selectively blocking the excitability of primary sensory nociceptor (pain-sensing) neurons by introducing the charged, membrane-impermeant lidocaine derivative QX-314 through the pore of the noxious-heat-sensitive TRPV1 channel. Here we show that charged sodium-channel blockers can be targeted into nociceptors by the application of TRPV1 agonists to produce a pain-specific local anaesthesia. QX-314 applied externally had no effect on the activity of sodium channels in small sensory neurons when applied alone, but when applied in the presence of the TRPV1 agonist capsaicin, QX-314 blocked sodium channels and inhibited excitability. Inhibition by co-applied QX-314 and capsaicin was restricted to neurons expressing TRPV1. Injection of QX-314 together with capsaicin into rat hindpaws produced a long-lasting (more than 2 h) increase in mechanical and thermal nociceptive thresholds. Long-lasting decreases in pain sensitivity were also seen with regional injection of QX-314 and capsaicin near the sciatic nerve; however, in contrast to the effect of lidocaine, the application of QX-314 and capsaicin together was not accompanied by motor or tactile deficits.
