生物谷报道:神经学家首次将感知冷暖的“冷纤维”可视化。“冷纤维”是从脊髓附近的神经元延伸到皮肤神经末端,来感觉不同类 型的“冷”。这项研究的结果刊登在12约19日的Journal of Neuroscience杂志上。
纤维能够回到神经元的一个位置,在那里,一种叫做TRPM8的蛋白质能够将一个冷信号传递给脊髓,然后传送到大脑。
冷纤维的概念很简单。例如,当牙医用压缩气体吹牙齿时,这种纤维能够从神经末端携带一个信号到达感觉神经元。神经元在将这个信号传递给大脑,然后患者会冷的发抖。
领导这项研究的南加州大学的David McKemy博士解释说,实际情况中,没有人真正看到一根特殊的冷纤维。
McKemy的研究通过运用遗传工程改造的小鼠解决了这个问题。这种小鼠的神经元表达携带一种荧光标记物的TRPM8蛋白。这种荧光标记能够照亮这些纤维。
McKemy的研究提供了首个感知冷、表达了TRPM8的神经元的图像。之前的研究已经证实,缺少TRPM8的小鼠丧失了它们的感觉冷的能力。
研究人员指出,人类和其他动物似乎具有向他的机制。通过跟踪荧光冷纤维,研究人员进一步证实TRPM8与几种感知“冷”类型有关。在牙齿中,与最初的刺痛和之后的疼痛有关的不同神经末梢都能与TRPM8反应。
感觉薄荷糖的令人愉快的凉爽、冰块在皮肤上的刺冷、受伤后的强烈的冷感都与TRPM8有关。
将TRPM8清除不会消除感知所有类型冷的感知能力。极端的冷不会活化TRPM8,而是会直接冻伤皮肤,进而启动许多其他警告环路。
McKemy表示,冷能够活化这些凉爽和冷细胞,我们的更高级的认知中心能够加工这些冷信号和疼信号,进而我们在会感觉等冷和痛。
这项研究的一个目的是了解感觉得分子机制,并希望能够开发出用于缓解慢性疼痛的更有效、安全的药物。
原始出处:
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: mckemy@usc.edu
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