Löken Line S, Duff Eugene P, Tracey Irene
Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford , United Kingdom.
Department of Anatomy, University of California , San Francisco, California.
J Neurophysiol. 2017 Dec 1;118(6):3360-3369. doi: 10.1152/jn.00977.2016. Epub 2017 Sep 27.
In the setting of injury, myelinated primary afferent fibers that normally signal light touch are thought to switch modality and instead signal pain. In the absence of injury, touch is perceived as more intense when firing rates of Aβ afferents increase. However, it is not known if varying the firing rates of Aβ afferents have any consequence to the perception of dynamic mechanical allodynia (DMA). We hypothesized that, in the setting of injury, the unpleasantness of DMA would be intensified as the firing rates of Aβ afferents increase. Using a stimulus-response protocol established in normal skin, where an increase in brush velocity results in an increase of Aβ afferent firing rates, we tested if brush velocity modulated the unpleasantness of capsaicin-induced DMA. We analyzed how changes in estimated low-threshold mechanoreceptor firing activity influenced perception and brain activity (functional MRI) of DMA. Brushing on normal skin was perceived as pleasant, but brushing on sensitized skin produced both painful and pleasant sensations. Surprisingly, there was an inverse relationship between Aβ firing rates and unpleasantness such that brush stimuli that produced low firing rates were most painful and those that elicited high firing rates were rated as pleasant. Concurrently to this, we found increased cortical activity in response to low Aβ firing rates in regions previously implicated in pain processing during brushing of sensitized skin, but not normal skin. We suggest that Aβ signals do not merely switch modality to signal pain during injury. Instead, they exert a high- and low-frequency-dependent dual role in the injured state, with respectively both pleasant and unpleasant consequences. NEW & NOTEWORTHY We suggest that Aβ signals do not simply switch modality to signal pain during injury but play a frequency-dependent and dual role in the injured state with both pleasant and unpleasant consequences. These results provide a framework to resolve the apparent paradox of how touch can inhibit pain, as proposed by the Gate Control Theory and the existence of dynamic mechanical allodynia.
在损伤情况下,通常传递轻触觉信号的有髓初级传入纤维被认为会改变其功能模式,转而传递疼痛信号。在没有损伤时,当Aβ传入纤维的放电频率增加时,触觉会被感知为更强烈。然而,尚不清楚改变Aβ传入纤维的放电频率是否会对动态机械性异常性疼痛(DMA)的感知产生任何影响。我们假设,在损伤情况下,随着Aβ传入纤维放电频率的增加,DMA的不适感会加剧。我们使用在正常皮肤中建立的刺激-反应方案,即刷擦速度增加会导致Aβ传入纤维放电频率增加,来测试刷擦速度是否会调节辣椒素诱导的DMA的不适感。我们分析了估计的低阈值机械感受器放电活动的变化如何影响DMA的感知和大脑活动(功能磁共振成像)。在正常皮肤上刷擦被感知为愉悦的,但在致敏皮肤上刷擦会产生疼痛和愉悦两种感觉。令人惊讶的是,Aβ放电频率与不适感之间存在反比关系,即产生低放电频率的刷擦刺激最疼痛,而引发高放电频率的刺激则被评为愉悦。与此同时,我们发现在刷擦致敏皮肤而非正常皮肤时,先前与疼痛处理相关的区域对低Aβ放电频率的反应中皮质活动增加。我们认为,Aβ信号在损伤期间不仅仅是改变功能模式来传递疼痛信号。相反,它们在损伤状态下发挥高频和低频依赖性的双重作用,分别产生愉悦和不愉悦的后果。新发现与值得注意之处我们认为,Aβ信号在损伤期间并非简单地改变功能模式来传递疼痛信号,而是在损伤状态下发挥频率依赖性的双重作用,产生愉悦和不愉悦的后果。这些结果为解决门控理论提出的触摸如何能抑制疼痛以及动态机械性异常性疼痛的存在这一明显矛盾提供了一个框架。