生物谷報(bào)道：神經(jīng)學(xué)家首次將感知冷暖的“冷纖維”可視化,。“冷纖維”是從脊髓附近的神經(jīng)元延伸到皮膚神經(jīng)末端，來感覺不同類 型的“冷”,。這項(xiàng)研究的結(jié)果刊登在12約19日的Journal of Neuroscience雜志上,。
纖維能夠回到神經(jīng)元的一個(gè)位置，在那里,，一種叫做TRPM8的蛋白質(zhì)能夠?qū)⒁粋€(gè)冷信號(hào)傳遞給脊髓,，然后傳送到大腦。
冷纖維的概念很簡(jiǎn)單,。例如,，當(dāng)牙醫(yī)用壓縮氣體吹牙齒時(shí)，這種纖維能夠從神經(jīng)末端攜帶一個(gè)信號(hào)到達(dá)感覺神經(jīng)元,。神經(jīng)元在將這個(gè)信號(hào)傳遞給大腦,，然后患者會(huì)冷的發(fā)抖。
領(lǐng)導(dǎo)這項(xiàng)研究的南加州大學(xué)的David McKemy博士解釋說,，實(shí)際情況中,，沒有人真正看到一根特殊的冷纖維。
McKemy的研究通過運(yùn)用遺傳工程改造的小鼠解決了這個(gè)問題,。這種小鼠的神經(jīng)元表達(dá)攜帶一種熒光標(biāo)記物的TRPM8蛋白,。這種熒光標(biāo)記能夠照亮這些纖維。
McKemy的研究提供了首個(gè)感知冷,、表達(dá)了TRPM8的神經(jīng)元的圖像,。之前的研究已經(jīng)證實(shí)，缺少TRPM8的小鼠喪失了它們的感覺冷的能力,。
研究人員指出,，人類和其他動(dòng)物似乎具有向他的機(jī)制。通過跟蹤熒光冷纖維，研究人員進(jìn)一步證實(shí)TRPM8與幾種感知“冷”類型有關(guān),。在牙齒中,，與最初的刺痛和之后的疼痛有關(guān)的不同神經(jīng)末梢都能與TRPM8反應(yīng)。
感覺薄荷糖的令人愉快的涼爽,、冰塊在皮膚上的刺冷,、受傷后的強(qiáng)烈的冷感都與TRPM8有關(guān)。
將TRPM8清除不會(huì)消除感知所有類型冷的感知能力,。極端的冷不會(huì)活化TRPM8,，而是會(huì)直接凍傷皮膚，進(jìn)而啟動(dòng)許多其他警告環(huán)路,。
McKemy表示,，冷能夠活化這些涼爽和冷細(xì)胞，我們的更高級(jí)的認(rèn)知中心能夠加工這些冷信號(hào)和疼信號(hào),，進(jìn)而我們?cè)跁?huì)感覺等冷和痛。
這項(xiàng)研究的一個(gè)目的是了解感覺得分子機(jī)制,，并希望能夠開發(fā)出用于緩解慢性疼痛的更有效,、安全的藥物。
原始出處：
The Journal of Neuroscience, December 19, 2007, 27(51):14147-14157; doi:10.1523/JNEUROSCI.4578-07.2007
Diversity in the Neural Circuitry of Cold Sensing Revealed by Genetic Axonal Labeling of Transient Receptor Potential Melastatin 8 Neurons
Yoshio Takashima,1 Richard L. Daniels,1 Wendy Knowlton,1 James Teng,3 Emily R. Liman,1,2 and David D. McKemy1,2,3
1Neuroscience Graduate Program, 2Neurobiology Section, Department of Biological Sciences, and 3School of Dentistry, University of Southern California, Los Angeles, California 90089
Correspondence should be addressed to Dr. David D. McKemy, 3641 Watt Way, HNB 228, University of Southern California, Los Angeles, CA 90089. Email: [email protected]
Sensory nerves detect an extensive array of somatosensory stimuli, including environmental temperatures. Despite activating only a small cohort of sensory neurons, cold temperatures generate a variety of distinct sensations that range from pleasantly cool to painfully aching, prickling, and burning. Psychophysical and functional data show that cold responses are mediated by both C- and A-fibers with separate peripheral receptive zones, each of which likely provides one or more of these distinct cold sensations. With this diversity in the neural basis for cold, it is remarkable that the majority of cold responses in vivo are dependent on the cold and menthol receptor transient receptor potential melastatin 8 (TRPM8). TRPM8-null mice are deficient in temperature discrimination, detection of noxious cold temperatures, injury-evoked hypersensitivity to cold, and nocifensive responses to cooling compounds. To determine how TRPM8 plays such a critical yet diverse role in cold signaling, we generated mice expressing a genetically encoded axonal tracer in TRPM8 neurons. Based on tracer expression, we show that TRPM8 neurons bear the neurochemical hallmarks of both C- and A-fibers, and presumptive nociceptors and non-nociceptors. More strikingly, TRPM8 axons diffusely innervate the skin and oral cavity, terminating in peripheral zones that contain nerve endings mediating distinct perceptions of innocuous cool, noxious cold, and first- and second-cold pain. These results further demonstrate that the peripheral neural circuitry of cold sensing is cellularly and anatomically complex, yet suggests that cold fibers, caused by the diverse neuronal context of TRPM8 expression, use a single molecular sensor to convey a wide range of cold sensations.
Key words: TRPM8; cold temperatures; menthol; neural circuit; sensory neuron; transgenic
