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Activation of sleeping nociceptors (CMi) is a crucial mechanism for the peripheral component of intense and long\u2010lasting pain. Thus, activation of CMi might be especially effective in itch reduction. Electrical stimulation using sinusoidal pulses activates CMi with tolerable pain intensity, whereas short rectangular pulses with low intensity do not. In humans, histaminergic itch is mediated by histamine\u2010sensitive CMi, whereas other pruritogens activate polymodal nociceptors (CM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a psychophysical approach in a balanced crossover repeated\u2010measures design in healthy volunteers, we activated nociceptors by two different electrical stimulation paradigms via a matrix electrode: 4\u2009Hz sinusoidal pulses that activate C\u2010nociceptors including CMi or 4\u2009Hz rectangular stimuli to activate nociceptors excluding CMi. After 5\u2010min stimulation, itch was induced by either histamine iontophoresis or application of cowhage spicules. Itch ratings were assessed via a numerical rating scale (NRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Electrical 4\u2009Hz sine wave stimulation (0.1\u2009mA) with low pain ratings of 1.5 (NRS; 0\u201310) induced an axon reflex erythema (3\u2009cm<jats:sup>2<\/jats:sup>), indicating activation of CMi, whereas rectangular 0.2\u2009ms pulses (average 0.91\u2009mA) with the same pain rating did not. Both electrical stimulation paradigms reduced itch magnitude over time evoked by either histamine or cowhage to a similar extent. Peak maximum itch evoked by histamine was reduced by both stimulation paradigms, but not cowhage maximum itch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Since electrical stimulation with the rectangular pulse paradigm reduces itch to a similar extent as the sine wave stimulation paradigm, the input of CMi is not necessarily required for itch suppression. The input of A\u2010fibres and polymodal nociceptors, similarly, as also achieved by scratching, seems to be sufficient for both forms of chemically evoked itch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Since activation of CMi does not provide additional benefit for itch suppression, spinal pain pathways transmitted via CM versus CMi have differential effects on itch\u2010processing circuits. This is important knowledge for using electrical matrix stimulation as itch suppressor since activation of sleeping nociceptors either requires significantly painful stimulation paradigms or specialized stimulation paradigms as sinusoidal pulses. An alternative approach using half\u2010sine wave pulses with low pain intensity activating specifically polymodal nociceptors to suppress itch via matrix electrode stimulation may be considered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.2177","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T08:45:35Z","timestamp":1694853935000},"page":"285-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Electrical matrix stimulation suppresses acute itch independently of activation of sleeping nociceptors"],"prefix":"10.1002","volume":"28","author":[{"given":"M.","family":"Schwarzenauer","sequence":"first","affiliation":[{"name":"IZKF Research Group Neuroscience Medical Faculty RWTH Aachen University  Aachen Germany"},{"name":"Department of Palliative Medicine Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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