Sensory transduction in peripheral nerve axons elicits ectopic action potentials
Sensory transduction in peripheral nerve axons elicits ectopic action potentials
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DOI：
10.1523/jneurosci.1627-08.2008
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发表时间：
2008-06-11
影响因子：
5.3
通讯作者：
Reeh, Peter W.
中科院分区：
文献类型：
--
作者：
Hoffmann, Tal;Sauer, Susanne K.;Reeh, Peter W.
在离体大鼠坐骨神经中，无髓鞘轴突的感觉特性先前已经通过测量刺激的神经肽释放来响应伤害性刺激而被揭示。此外，炎症介质引起的轴突致敏作用已被证明并显示依赖于热和质子激活的离子通道瞬时受体电位香草素受体-1。目前还不清楚这种反应是否伴随着异位产生的动作电位，这可能在疼痛性神经病变中发挥关键作用。我们探讨了这一假设，使用离体小鼠皮肤神经制备。这种方法使我们能够直接比较周围神经轴突的感觉特性，其特征在于在感受野中的皮肤末梢，使用传播的动作电位作为轴突激活的指标。从51 mechanosensitive小鼠C-纤维的单纤维记录显示，大多数的多模态伤害感受器响应与编码放电率分级加热的皮肤感受野（n = 38），以及隐神经携带的纤维调查（n = 25; 66%）。轴突热反应在阈值和放电率方面优于感受野的热反应（41.5 +/- 4.3 ℃;在20 s 32-48 ℃范围内刺激中7.7 +/- 9.6个尖峰）。相比之下，轴突机械敏感性差，冷敏感性更少见。总之，周围神经轴突表现出的感觉转导能力类似于他们的伤害性终端在皮肤方面的有害热，虽然没有机械和冷敏感性。如果轴突热阈值下降到体温，这可能成为异位放电和疼痛的来源，就像周围神经中的炎症样过程中的情况一样。
Sensory properties of unmyelinated axons in the isolated rat sciatic nerve have been revealed previously by measuring stimulated neuropeptide release in response to noxious stimuli. In addition, axonal sensitization by inflammatory mediators has been demonstrated and shown to depend on the heat-and proton-activated ion channel transient receptor potential vanilloid receptor-1. It was unclear whether this responsiveness is accompanied by ectopic generation of action potentials, which may play a crucial role in painful neuropathies. We explored this hypothesis using the isolated mouse skin-nerve preparation. This method enabled us to directly compare the sensory properties of axons in the peripheral nerve with their characterized cutaneous terminals in the receptive field using propagated action potentials as an index of axonal activation. Single-fiber recordings from 51 mechanosensitive mouse C-fibers revealed that a majority of the polymodal nociceptors responded with an encoding discharge rate to graded heating of the cutaneous receptive field (n = 38) as well as of the saphenous nerve carrying the fiber under investigation (n = 25; 66%). Axonal heat responses paralleled those of the receptive fields with regard to thresholds and discharge rates (41.5 +/- 4.3 degrees C; 7.7 +/- 9.6 spikes in a 20 s 32-48 degrees C ranged stimulation). In contrast, axonal mechanosensitivity was poor and noxious cold sensitivity more rarely encountered. In conclusion, peripheral nerve axons exhibit sensory transduction capacities similar to their nociceptive terminals in the skin with respect to noxious heat, although not to mechanical and cold sensitivity. This may become a source of ectopic discharge and pain if axonal heat threshold drops to body temperature, as may be the case during inflammation-like processes in peripheral nerves.