Haugan F, Wibrand K, Fiskå A, Bramham C R, Tjølsen A
Department of Biomedicine, University of Bergen, Bergen, Norway.
Neuroscience. 2008 Jul 17;154(4):1568-75. doi: 10.1016/j.neuroscience.2008.05.010. Epub 2008 May 21.
Long term facilitation (LTF) of C-fiber-evoked firing of wide dynamic range neurons in the spinal dorsal horn in response to conditioning stimulation (CS) of afferent fibers is a widely studied cellular model of spinal nociceptive sensitization. Although 100 Hz CS of primary afferent fibers is commonly used to induce spinal cord LTF, this frequency exceeds the physiological firing range. Here, we examined the effects of electrical stimulation of the sciatic nerve within the physiological frequency range on the magnitude and stability of the C-fiber-evoked responses of wide dynamic range neurons and the expression of immediate early genes (c-fos, zif268, and Arc) in anesthetized rats. Stimulation frequencies of 3, 30 and 100 Hz all induced facilitation of similar magnitude as recorded at 1 h post-CS. Strikingly, however, 3 Hz-induced potentiation of the C-fiber responses was decremental, whereas both 30 and 100 Hz stimulation resulted in stable, non-decremental facilitation over 3 h of recording. The number of dorsal horn neurons expressing c-fos, but not zif268 or Arc, was significantly elevated after 3 Hz CS and increased proportionally with stimulation rate. In contrast, a stable LTF of C-fiber responses was obtained at 30 and 100 Hz CS, and at these frequencies there was a sharp increase in zif268 expression and appearance of Arc-positive neurons. The results show that response facilitation can be induced by stimulation frequencies in the physiological range (3 and 30 Hz). Three hertz stimulation induced the early phase of LTF, but the responses were decremental. Arc and zif268, two genes previously coupled to LTP of synaptic transmission in the adult brain, are upregulated at the same frequencies that give stable LTF (30 and 100 Hz). This frequency-dependence is important for understanding how the afferent firing pattern affects neuronal plasticity and nociception in the spinal dorsal horn.
脊髓背角中广动力范围神经元对传入纤维条件刺激（CS）产生的C纤维诱发放电的长期易化（LTF）是一种被广泛研究的脊髓伤害性感受敏化的细胞模型。虽然通常使用100Hz的初级传入纤维CS来诱导脊髓LTF，但该频率超出了生理放电范围。在此，我们研究了在生理频率范围内电刺激坐骨神经对麻醉大鼠广动力范围神经元C纤维诱发反应的幅度和稳定性以及即刻早期基因（c-fos、zif268和Arc）表达的影响。3Hz、30Hz和100Hz的刺激频率均诱导出与CS后1小时记录到的相似幅度的易化。然而，令人惊讶的是，3Hz诱导的C纤维反应增强是递减的，而30Hz和100Hz刺激在记录的3小时内均导致稳定的、非递减的易化。3Hz CS后，表达c-fos但不表达zif268或Arc的背角神经元数量显著增加，且与刺激频率成比例增加。相比之下，在30Hz和100Hz CS时获得了稳定的C纤维反应LTF，在这些频率下，zif268表达急剧增加且出现Arc阳性神经元。结果表明，生理频率范围（3Hz和30Hz）内的刺激频率可诱导反应易化。3Hz刺激诱导了LTF的早期阶段，但反应是递减的。Arc和zif268这两个先前与成年大脑中突触传递的LTP相关的基因，在产生稳定LTF的相同频率（30Hz和100Hz）下上调。这种频率依赖性对于理解传入放电模式如何影响脊髓背角中的神经元可塑性和伤害感受至关重要。
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