Transcutaneous Slowly Depolarizing Currents Elicit Pruritus in Patients with Atopic Dermatitis

Abstract

Slowly depolarizing currents applied for one minute have been shown to activate C-nociceptors and provoke increasing pain in patients with neuropathy. This study examined the effect of transcutaneous slowly depolarizing currents on pruritus in patients with atopic dermatitis. C-nociceptor-specific electrical stimulation was applied to areas of eczema-affected and non-affected skin in 26 patients with atopic dermatitis. Single half-sine wave pulses (500 ms, 0.2–1 mA) induced itch in 9 patients in eczema-affected areas of the skin (numerical rating scale 5 ± 1), but pain in control skin (numerical rating scale 6±1).Sinusoidal stimuli (4 Hz, 10 pulses, 0.025–0.4 mA) evoked itch in only 3 patients in eczema-affected areas of the skin but on delivering pulses for one minute (0.05–0.2 mA) 48% of the patients ( n = 12) reported itch with numerical rating scale 4 ± 1 in areas of eczema-affected skin. The number of patients reporting itch in eczema-affected areas of the skin increased with longer stimulation ( p < 0.005). These results demonstrate a reduced adaptation of peripheral C-fibres conveying itch in patients with atopic dermatitis. Sensitized spinal itch processing had been suggested before in atopic dermatitis patients, and this could be present also in our patients who therefore might benefit from centrally acting antipruritic therapy.

How Do Neurons Signal Itch?

“…Beyond the direct involvement of GRP in the generation of pruritus it may render the spinal cord more susceptible for evoked pruritus: in particular acute electrical stimulation may provoke mainly pain in healthy volunteers. However, in chronic itch patients it might also evoke itch (64) suggesting that the spinal cord processing of itch has been facilitated in these patients potentially be previous release of GRP. For experimental stimulation protocols therefore phasic and tonic stimulation paradigms and possible carry-over effects by spinal GRP release need to be considered.…”

Electrically Evoked Itch in Human Subjects

“…Importantly, when the sine wave pulses were delivered continuously for 1 min (4 Hz, max. 0.2 mA) to eczematous skin sites, the number of patients reporting itch increased progressively the longer the stimulation lasted, resulting in about 50% of AD patients perceiving an itch at 1 min (all of them also perceived half-sine wave itch) (28). When stimulating non-affected skin sites only three patients reported itch.…”

“…Notably, low-threshold unmyelinated tactile afferents also respond to that type of stimulus (34) but this fiber class is associated primarily with social touch rather than pain or itch processing (37,38). In contrast, "silent" and "polymodal" C-nociceptors are activated by 4 Hz sine wave pulses (33,36) of which "silent" nociceptors respond with one action potential per sinusoidal cycle compared (28) Summary and references of the electrical stimulation protocols. Note that with a rectangular stimulation paradigm of 0.25 Hz and 0.5 ms pulse duration the transcutaneous electrical thresholds were >9 mA for C-nociceptor stimulation (electrode covering 30 mm 2 ) (30).…”

“…In a recent study, we used this electrical stimulation protocol of differential ("polymodal" and "silent") C-nociceptor activation to investigate electrically evoked sensations in AD patients (28). Half-sine wave and sine wave stimuli were delivered to eczematous skin areas that had been particularly itchy before the investigation, and the corresponding sensation was compared to the electrically induced responses obtained from the patients' non-affected (if possible site matched) skin sites.…”

“…Independent of the exact coding mechanism of pruritus, it is a striking observation that AD patients often feel itch during stimulation of their eczematous skin upon a stimulus that is normally perceived as painful (28,58). One likely mechanism of such a shift from pain to itch can be a changed central processing of the pruriceptive and/or nociceptive input in AD.…”