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Modulation of Itch by Conditioning Itch and Pain Stimulation in Healthy Humans

  • Hjalte H. Andersen
    Affiliations
    Laboratory for Experimental Cutaneous Pain Research, Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
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  • Antoinette I.M. van Laarhoven
    Affiliations
    Laboratory for Experimental Cutaneous Pain Research, Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark

    Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioral Sciences, Leiden University, Leiden, The Netherlands

    Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands

    Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
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  • Jesper Elberling
    Affiliations
    Department of Dermato-Allergology, Copenhagen University Hospital, Herlev-Gentofte, Copenhagen, Denmark
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  • Lars Arendt-Nielsen
    Correspondence
    Address reprint requests to Lars Arendt-Nielsen, PhD, Fredrik Bajers Vej 7, Bld D3, Aalborg E DK-9220, Denmark.
    Affiliations
    Laboratory for Experimental Cutaneous Pain Research, Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
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      Highlights

      • Little is known about descending control of itch and techniques to assess conditioned itch modulation in humans.
      • In this study conditioned itch modulation was systemically tested using psychophysical paradigms.
      • A prioritization favoring pain-induced, rather than itch-induced, endogenous modulation of itch and pain was found.
      • Investigations of pain-evoked conditioned itch modulation in chronic itch patients are warranted.

      Abstract

      Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P < .001), but not by the conditioning itch stimulus (negative control condition). Itch was significantly reduced (conditioned itch modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P < .001), whereas conditioning itch stimulation only marginally reduced itch. Endogenous descending itch inhibition through mechanisms that are independent of segmental gating can be readily evoked by heterotopic conditioning pain stimulation. However, robust descending inhibition of itch cannot be evoked with conditioning itch stimulation.

      Perspective

      The study showed a hierarchical prioritization favoring pain-induced central descending modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted.

      Key words

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