Modality-specific sensory changes in humans after the induction of long-term potentiation (LTP) in cutaneous nociceptive pathways

The impact of long-term potentiation (LTP) in nociceptive pathways on somatosensory perception was examined by means of quantitative sensory testing (QST) in the ventral forearm of 12 healthy human subjects. Electrical high-frequency stimulation of the forearm skin (HFS; 5 × 1 s at 100 Hz and 10 × detection threshold) led to an abrupt increase of pain to single electrical test stimuli, which were applied through the same electrode (perceptual LTP +72%, p < 0.01). Perceptual LTP outlasted the 1-h observation period. The effects of HFS on somatosensory perception of natural test stimuli in the conditioned skin area were restricted to mechanical submodalities. Subjects exhibited a significant decrease of pain threshold and an increase of pain ratings to suprathreshold pinprick stimuli (p < 0.01). In 5 out of 12 subjects (42%) light tactile stimuli led to painful sensations (dynamic mechanical allodynia). Furthermore, a small but significant decrease of threshold to blunt pressure stimuli (p < 0.05) was found. In contrast, all thermal modalities comprising cold and warm detection thresholds, cold and heat pain thresholds as well as pain summation (perceptual wind up) remained unaltered. These data show that HFS of peptidergic cutaneous C-fiber afferents predominantly modulates Aδ- and Aβ-fiber mediated somatosensory functions, suggesting that LTP in nociceptive pathways enhances human pain sensitivity via interaction of two afferent pathways (extrinsic sensitization).