美國科學家近日研究發(fā)現，辣椒中的辣椒素（Capsaicin）可幫助某些麻醉劑進入細胞,。這一研究將有助于開發(fā)新的治療手段——緩解疼痛而不會導致麻痹和暫時性的癱瘓,。相關論文發(fā)表在10月4日的《自然》上。
目前,，許多局部麻醉劑的工作原理是阻礙鈉離子通道以緩解疼痛。但是,，這一方法存在很多副作用,。它會關閉傳輸觸覺信息及控制運動信息的神經活動，這就是為什么很多人在進行口腔局部麻醉后,，出現流口水,、胡言亂語以及舌頭麻木等狀況的原因,。
在最新的研究中，美國哈佛醫(yī)學院的神經學家Bruce Bean發(fā)現,，辣椒素能夠開啟痛覺神經上的TRPV-1通道,，并且該通道異常寬大，看起來似乎能讓麻醉劑從中通過,。Bean和同事緊接著在小鼠身上進行了實驗,，他們首先向小鼠坐骨神經附近單獨注射了局部麻醉劑QX-314（它的作用機制也是阻礙鈉離子通道），小鼠一如所料表現出正常的疼痛反應,；接下來他們在注射QX-314之后又注射了辣椒素,，這樣TRPV-1通道被打開，小鼠的疼痛感覺消失,，這種止痛效應持續(xù)了90分鐘,。而且，注射辣椒素不會像注射傳統(tǒng)局部麻醉劑利多卡因（lidocaine）那樣會損害小鼠后肢的活動能力,。
Bean表示,，這種方法將來可能有助于醫(yī)生選擇性地減少疼痛，而不會導致麻痹或妨礙運動,。他說：“首先躍入我腦海的例子就是分娩,。”
美國加州大學舊金山分校的神經生理學家David Julius表示，這一觀點雖然簡單卻很精致,。不過他提醒說,，目前還不能保證該方法能很好地在人身上應用。其中一個問題就是,，注射QX-314能否完全抵消辣椒素帶來的火燒火燎的痛覺,。針對這一問題，Bean表示,，他已計劃研究其它類似藥物,，以發(fā)現比QX-314效率更高的替代品。（科學網 梅進/編譯）
原始出處:
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: [email protected]).
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.
