Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans

Hjalte Holm Andersen, Antoinette I. M. van Laarhoven, Frederik D. Justesen, Jacob B. Pedersen, Laurits L Sørensen, Line P. Jensen, Lars Arendt-Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50 Hz stimulation, 100 μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy male volunteers a placebo-controlled, 24-h 8% topical capsaicin-induced defunctionalization of capsaicin-sensitive (transient receptor potential V1-positive, ‘TRPV1’ +) cutaneous fibers was performed. Histaminergic itch (1% solution introduced by a prick test lancet) was provoked as a positive control condition. Capsaicin pretreatment induced profound loss of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, indicative of efficient TRPV1-fiber defunctionalization (all outcomes: P < 0.0001). The topical capsaicin robustly, and with similar efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (−89 ± 4.1% and −78 ± 4.9%, respectively, both: P < 0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.

Original languageEnglish
JournalNeuroscience Letters
Volume666
Pages (from-to)186-189
Number of pages4
ISSN0304-3940
DOIs
Publication statusPublished - 14 Feb 2018

Fingerprint

Capsaicin
Skin
Unmyelinated Nerve Fibers
Placebos
Transcutaneous Electric Nerve Stimulation
Vasopressin Receptors
Pain Threshold
Histamine
Electric Stimulation
Healthy Volunteers
Hot Temperature
Pain

Keywords

  • C-Fibers
  • Capsaicin
  • Histamine
  • Itch
  • Nociceptors
  • Pruriceptors
  • TPRV1

Cite this

Andersen, H. H., van Laarhoven, A. I. M., Justesen, F. D., Pedersen, J. B., Sørensen, L. L., Jensen, L. P., & Arendt-Nielsen, L. (2018). Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans. Neuroscience Letters, 666, 186-189. https://doi.org/10.1016/j.neulet.2017.11.061
Andersen, Hjalte Holm ; van Laarhoven, Antoinette I. M. ; Justesen, Frederik D. ; Pedersen, Jacob B. ; Sørensen, Laurits L ; Jensen, Line P. ; Arendt-Nielsen, Lars. / Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans. In: Neuroscience Letters. 2018 ; Vol. 666. pp. 186-189.
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abstract = "Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50 Hz stimulation, 100 μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy male volunteers a placebo-controlled, 24-h 8{\%} topical capsaicin-induced defunctionalization of capsaicin-sensitive (transient receptor potential V1-positive, ‘TRPV1’ +) cutaneous fibers was performed. Histaminergic itch (1{\%} solution introduced by a prick test lancet) was provoked as a positive control condition. Capsaicin pretreatment induced profound loss of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, indicative of efficient TRPV1-fiber defunctionalization (all outcomes: P < 0.0001). The topical capsaicin robustly, and with similar efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (−89 ± 4.1{\%} and −78 ± 4.9{\%}, respectively, both: P < 0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.",
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Andersen, HH, van Laarhoven, AIM, Justesen, FD, Pedersen, JB, Sørensen, LL, Jensen, LP & Arendt-Nielsen, L 2018, 'Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans' Neuroscience Letters, vol. 666, pp. 186-189. https://doi.org/10.1016/j.neulet.2017.11.061

Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans. / Andersen, Hjalte Holm; van Laarhoven, Antoinette I. M.; Justesen, Frederik D.; Pedersen, Jacob B.; Sørensen, Laurits L; Jensen, Line P.; Arendt-Nielsen, Lars.

In: Neuroscience Letters, Vol. 666, 14.02.2018, p. 186-189.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans

AU - Andersen, Hjalte Holm

AU - van Laarhoven, Antoinette I. M.

AU - Justesen, Frederik D.

AU - Pedersen, Jacob B.

AU - Sørensen, Laurits L

AU - Jensen, Line P.

AU - Arendt-Nielsen, Lars

PY - 2018/2/14

Y1 - 2018/2/14

N2 - Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50 Hz stimulation, 100 μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy male volunteers a placebo-controlled, 24-h 8% topical capsaicin-induced defunctionalization of capsaicin-sensitive (transient receptor potential V1-positive, ‘TRPV1’ +) cutaneous fibers was performed. Histaminergic itch (1% solution introduced by a prick test lancet) was provoked as a positive control condition. Capsaicin pretreatment induced profound loss of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, indicative of efficient TRPV1-fiber defunctionalization (all outcomes: P < 0.0001). The topical capsaicin robustly, and with similar efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (−89 ± 4.1% and −78 ± 4.9%, respectively, both: P < 0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.

AB - Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50 Hz stimulation, 100 μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy male volunteers a placebo-controlled, 24-h 8% topical capsaicin-induced defunctionalization of capsaicin-sensitive (transient receptor potential V1-positive, ‘TRPV1’ +) cutaneous fibers was performed. Histaminergic itch (1% solution introduced by a prick test lancet) was provoked as a positive control condition. Capsaicin pretreatment induced profound loss of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, indicative of efficient TRPV1-fiber defunctionalization (all outcomes: P < 0.0001). The topical capsaicin robustly, and with similar efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (−89 ± 4.1% and −78 ± 4.9%, respectively, both: P < 0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.

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KW - Histamine

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Andersen HH, van Laarhoven AIM, Justesen FD, Pedersen JB, Sørensen LL, Jensen LP et al. Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans. Neuroscience Letters. 2018 Feb 14;666:186-189. https://doi.org/10.1016/j.neulet.2017.11.061