Line S Löken, Eugene P Duff, Irene Tracey

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 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 increased 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 mechanoreceptor firing activity influenced perception and brain activity (fMRI) 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, we found increased cortical activity in response to low Aβ firing rates in regions previously implicated in pain processing while brushing sensitized 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.