Chen Chih-Li, Broom Daniel C, Liu Yang, de Nooij Joriene C, Li Zhe, Cen Chuan, Samad Omar Abdel, Jessell Thomas M, Woolf Clifford J, Ma Qiufu
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
Neuron. 2006 Feb 2;49(3):365-77. doi: 10.1016/j.neuron.2005.10.036.
In mammals, the perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by nociceptive sensory neurons. The molecular mechanisms responsible for the specification of distinct sensory modality are, however, largely unknown. We show here that Runx1, a Runt domain transcription factor, is expressed in most nociceptors during embryonic development but in adult mice, becomes restricted to nociceptors marked by expression of the neurotrophin receptor Ret. In these neurons, Runx1 regulates the expression of many ion channels and receptors, including TRP class thermal receptors, Na+-gated, ATP-gated, and H+-gated channels, the opioid receptor MOR, and Mrgpr class G protein coupled receptors. Runx1 also controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a finding with implications for pain therapy.
在哺乳动物中，疼痛的感知是由伤害性刺激通过伤害性感觉神经元表达的特殊离子通道和受体进行转导而启动的。然而，负责区分不同感觉模式的分子机制在很大程度上尚不清楚。我们在此表明，Runx1是一种Runt结构域转录因子，在胚胎发育过程中在大多数伤害感受器中表达，但在成年小鼠中，局限于以神经营养因子受体Ret表达为标志的伤害感受器。在这些神经元中，Runx1调节许多离子通道和受体的表达，包括TRP类热受体、钠门控、ATP门控和氢门控通道、阿片受体MOR以及Mrgpr类G蛋白偶联受体。Runx1还控制脊髓中伤害性传入纤维的板层特异性支配模式。此外，缺乏Runx1的小鼠在热痛和神经性疼痛方面表现出特定缺陷。因此，Runx1协调了大量伤害感受器的表型，这一发现对疼痛治疗具有重要意义。
