Neural activation during experimental allodynia: a functional magnetic resonance imaging study

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Abstract
Pain induced by gentle stroking, i.e. dynamic–mechanical allodynia, is one of the most distressing symptoms of neuropathic pain. The underlying neuronal pathways are still a matter of debate. Here, we investigated the cortical activations associated with dynamic‐mechanical allodynia in an experimental human pain model by functional magnetic resonance imaging (fMRI). Large and stable areas of brush‐evoked allodynia were induced in 11 healthy subjects by topical capsaicin (2.5%, 30 min) application following local heating (45 °C for 5 min), thus combining both physical and chemical sensitization. During the fMRI experiments, allodynia was rekindled by local heat application (40 °C for 5 min) immediately before the allodynia testing. Brushing the untreated forearm (control condition) led to activations of the contralateral primary somatosensory cortex (S1), contralateral parietal association cortex (PA), bilateral secondary somatosensory cortices (S2) and insula (contralateral). Brushing the allodynic skin was painful and the cortical responses were partially overlapping with those induced by the nonpainful brush stimulation. Additionally, the contralateral inferior frontal cortex (IFC) and the ipsilateral insula were activated. Direct comparison between nonpainful brushing and brush‐evoked allodynia revealed significant increases in blood oxygenation level‐dependent (BOLD) signals in contralateral S1, PA, IFC and bilateral S2/insula during allodynia. This study highlights the importance of a cortical network comprising S1, PA, S2/insula and IFC in the processing of dynamic–mechanical allodynia in the human brain. Furthermore, it demonstrates that the combined heat/capsaicin model can be used successfully in the exploration of brain processes underlying stimulus‐evoked pain.