Colburn Raymond W, Lubin Mary Lou, Stone Dennis J, Wang Yan, Lawrence Danielle, D'Andrea Michael R, Brandt Michael R, Liu Yi, Flores Christopher M, Qin Ning
Analgesics Team, East Coast Research and Early Development, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Spring House, PA 19477-0776, USA.
Neuron. 2007 May 3;54(3):379-86. doi: 10.1016/j.neuron.2007.04.017.
Thermosensation is an essential sensory function that is subserved by a variety of transducer molecules, including those from the Transient Receptor Potential (TRP) ion channel superfamily. One of its members, TRPM8 (CMR1), a ligand-gated, nonselective cation channel, is activated by both cold and chemical stimuli in vitro. However, its roles in cold thermosensation and pain in vivo have not been fully elucidated. Here, we show that sensory neurons derived from TRPM8 null mice lack detectable levels of TRPM8 mRNA and protein and that the number of these neurons responding to cold (18 degrees C) and menthol (100 microM) is greatly decreased. Furthermore, compared with WT mice, TRPM8 null mice display deficiencies in certain behaviors, including icilin-induced jumping and cold sensation, as well as a significant reduction in injury-induced responsiveness to acetone cooling. These results suggest that TRPM8 may play an important role in certain types of cold-induced pain in humans.
温度感觉是一种重要的感觉功能，由多种转导分子介导，包括来自瞬时受体电位（TRP）离子通道超家族的分子。其中一个成员TRPM8（CMR1）是一种配体门控的非选择性阳离子通道，在体外可被寒冷和化学刺激激活。然而，其在体内冷觉和疼痛中的作用尚未完全阐明。在这里，我们表明，来自TRPM8基因敲除小鼠的感觉神经元缺乏可检测水平的TRPM8 mRNA和蛋白质，并且对寒冷（18摄氏度）和薄荷醇（100微摩尔）作出反应的这些神经元数量大幅减少。此外，与野生型小鼠相比，TRPM8基因敲除小鼠在某些行为上存在缺陷，包括艾西利定诱导的跳跃和冷觉，以及损伤诱导的对丙酮冷却反应性的显著降低。这些结果表明，TRPM8可能在人类某些类型的冷诱导疼痛中起重要作用。
