Dpto. Fisiología, Edificio de Medicina Universidad de Alcalá, Madrid, Spain.
Eur J Pain. 2013 Oct;17(9):1281-90. doi: 10.1002/j.1532-2149.2013.00302.x. Epub 2013 Mar 14.
Slowing refers to the gradual decrease in conduction velocity evoked by repetitive electrical stimuli. The underlying mechanisms are still poorly understood, and its physiological/pathological relevance scarcely discussed; however, changes in axonal conduction properties might unmask abnormal nociceptor function and alter the encoding time window at the spinal cord.
Here, we characterized and compared the slowing in isolated units recorded from intact and axotomized saphenous nerves from mice, in vitro. We evaluated the role of hyperpolarization-activated/HCN channel current, Ih , in the generation of slowing, by examining the effect of the specific Ih blocker ZD7288.
Based on their degree of slowing, intact C-fibres were classified as presumed nociceptors or non-nociceptors (>13% or <7% latency increase, respectively). Upon ZD7288 treatment, slowing was significantly augmented in 19/25 of the presumed C-nociceptors. In nerve-end neuromas, axotomized C-fibres could not be classified by their degree of slowing, which, in addition, was unrelated to the presence of ectopic mechanosensitivity. Axotomized fibres showed a ∼2.5-fold reduction in their slowing as compared with intact units and the effects of ZD7288 were more prominent, both in magnitude and percentage of sensitive fibres. Interestingly, in control conditions, all fibres sensitive to ZD7288 were more resistant to slowing.
Under our experimental conditions, slowing seems largely dependent on functional Ih . The marked decrease in slowing after axotomy in C-fibres fits with the increased expression of functional hyperpolarization-activated/HCN channel current and may underlie the analgesic effects of the specific Ih blocker ZD7288 previously described in neuropathic pain models.
迟滞是指重复电刺激引起的传导速度逐渐减慢。其潜在机制仍知之甚少，其生理/病理相关性也鲜有讨论；然而，轴突传导特性的变化可能会揭示异常伤害感受器的功能，并改变脊髓的编码时间窗口。
在这里，我们在体外对来自完整和切断的坐骨神经的分离单位进行了特征描述和比较。我们通过检查特定的 Ih 阻断剂 ZD7288 的作用，评估了超极化激活/HCN 通道电流 Ih 在迟滞产生中的作用。
根据其迟滞程度，完整的 C 纤维被分类为假定的伤害感受器或非伤害感受器（分别为潜伏期增加 >13%或 <7%）。在用 ZD7288 处理后，在 25 个假定的 C 伤害感受器中，有 19 个明显增强了迟滞。在神经末梢神经瘤中，不能根据其迟滞程度对切断的 C 纤维进行分类，而且，迟滞与异位机械敏感性的存在无关。与完整的单位相比，切断的纤维表现出约 2.5 倍的迟滞减少，并且 ZD7288 的作用更为明显，无论是在幅度还是敏感纤维的百分比上。有趣的是，在对照条件下，所有对 ZD7288 敏感的纤维对迟滞的抵抗力更强。
在我们的实验条件下，迟滞似乎在很大程度上依赖于功能性 Ih。C 纤维在切断后迟滞的明显减少与功能性超极化激活/HCN 通道电流的表达增加相吻合，这可能是先前在神经病理性疼痛模型中描述的特定 Ih 阻断剂 ZD7288 的镇痛作用的基础。
