Rapid flare development evoked by current frequency-dependent stimulation analyzed by full-field laser perfusion imaging

Abstract

We analyzed, with a new imaging technique, the rapid axon reflex flare responses in human skin upon transcutaneous delivery of electrical stimuli at 1, 5, 10 and 50 Hz in single bursts of five pulses each. Two-dimensional perfusion images covering an area of 8 x 8 cm(2) were captured at 25 Hz and their averages saved at 0.5 Hz. The stimulation caused an axon reflex flare (maximum 3 cm(2), 20 s after stimulation) that gradually resolved within 2 min. Maximum flare responses developed at 5 Hz, whereas pain ratings increased with stimulation frequency. The highest neuropeptide release at 5 Hz correlates to the discharge characteristics of mechanoinsensitive C-fibers, whereas the maximum pain intensity at 50 Hz may be attributed to the activation of A-delta fibers.

Long‐term facilitation of nociceptive withdrawal reflexes following low‐frequency conditioning electrical stimulation: A new model for central sensitization in humans

“…LFS, on the other hand, had previously been used mainly for eliciting long-term depression (LTD) of synaptic transmission in the hippocampus (Dudek and Bear, 1992;Mulkey and Malenka, 1992), although this paradigm was later shown to cause a similar effect in spinal cord synapses . In line with these observations, the present study shows that LFS at sufficient intensity activates thin nociceptive afferents, including C fibers as judged by the increase in cutaneous blood flow (Jänig and Lisney, 1989;Schmelz et al, 2000;Dusch et al, 2007). Moreover, it has been shown that a low-frequency afferent barrage at C-fiber intensity could also induce LTP at superficial (Ikeda et al, 2006;Drdla and Sandkühler, 2008) and deep (Haugan et al, 2008) dorsal horn neurons.…”

Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans

“…In this study, the mechano-insensitive C-fibers could also be recruited by the EPE. 10 Hz CES induced a higher and longer duration of blood flow changes compared with the other two conditioning paradigms which is in agreement with Dusch et al, 2007, who observed a greater flare response following low frequency electrical stimulation due to additional recruitment of mechano-insensitive C-fibers. Moreover, the peptidergic C-fiber nociceptors were found prone to be activated and conduct signals at lower frequencies (below 10 Hz) and the response latencies were increased with higher frequencies stimulation (Raymond et al, 1990).…”

“…2A), whereas 10 Hz and 200 Hz CES showed no significant changes of pain sensation over time. The results of the SF-MPQ during the conditioning process showed that the 10 Hz CES was less painful than the 100 Hz CES which may be related to the report that high frequency CES to a higher degree activates mechanosensitive nociceptors and A-δ fibers (Dusch et al, 2007). The pain ratings induced by 200 Hz CES were lower than 100 Hz CES for the first 10 sec stimulation.…”

Mechano-insensitive Nociceptors are Sufficient to Induce Histamine-induced Itch

“…Interestingly, the axon reflex flare, mediated by mechano-insensitive nociceptors (12), is already maximum at frequencies of approximately 2-5 Hz (19). Bursts of action potentials at higher frequencies are therefore expected to cause intense itching, but not necessarily a further increase in the axon reflex erythema.…”