Itch and pain share numerous mechanistic similarities. Patients with chronic itch conditions (for instance atopic dermatitis or neuropathic itch) often experience symptoms such as mechanical... Show moreItch and pain share numerous mechanistic similarities. Patients with chronic itch conditions (for instance atopic dermatitis or neuropathic itch) often experience symptoms such as mechanical alloknesis and hyperknesis. These dysesthesias are analogous to the pain-associated phenomena allodynia and hyperalgesia, which are often observed, for example, in neuropathic pain conditions. Mechanical itch dysesthesias represent abnormal sensory states (caused by neuroplastic changes), wherein considerable itch is evoked, for instance by light cutaneous stimuli such as from clothing (alloknesis), or where increased itch is perceived in response to normally itch-evoking stimuli (hyperknesis). These itch sensitization phenomena have been explored in experimental human studies, observed in chronic itch patients, and in animal models of itch. Limited attention has been paid to these sensory phenomena in clinical studies, and it is unknown how they respond to antipruritics. Psychophysical quantitative sensory testing can quantify the presence, severity, and spatial extent of itch dysesthesias in chronic itch patients, providing a proxy measurement of itch sensitization. This review outlines current assessment techniques, knowledge on the mechanisms of mechanical alloknesis and hyperknesis, and presents the diverse results derived from clinical studies exploring the presence of itch dysesthesias in chronic itch patients. A key role of quantitative sensory testing and neuronal sensitization in patients with chronic pain is accepted and used in clinical assessments. However, the precise mechanisms and potential clinical implications of itch sensitization in chronic itch patients remain to be evaluated. Show less
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... Show moreSpecially 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. Show less
Häufig erfahren Patienten positive (Placebo) oder negative (Nocebo) Behandlungseffekte aufgrund ihrer eigenen positiven oder negativen Erwartungen gegenüber der Behandlung. Die systematische... Show moreHäufig erfahren Patienten positive (Placebo) oder negative (Nocebo) Behandlungseffekte aufgrund ihrer eigenen positiven oder negativen Erwartungen gegenüber der Behandlung. Die systematische Erforschung dieser Placebo- und Noceboeffekte bei Pruritus hat erst in den letzten Jahren vermehrt Aufmerksamkeit erfahren. Experimentelle Studien belegen, dass Placebo- und Noceboeffekten bei Pruritus wie auch bei anderen Symptomen (z. B. Schmerz) Lernprozesse wie verbale Suggestionen und Konditionierung zugrunde liegen. Untersuchungen zum Phänomen „übertragbares Jucken“ zeigen, dass Beobachtungslernen bei Pruritus eine wichtige Rolle spielt, und suggerieren des Weiteren eine erhöhte Empfindlichkeit von Pruritus für Suggestionen und somit Placebo- und Noceboeffekte. Substanzielle Reduktionen von Pruritus in den Placebogruppen klinischer Studien implizieren, dass Placeboeffekte auch im klinischen Bereich eine maßgebliche Bedeutung haben. Der vorliegende Beitrag bietet eine Übersicht, wie Placebo- und Noceboeffekte bei Pruritus im wissenschaftlichen Bereich und im klinischen Alltag eingesetzt werden können. Show less
Itch is a prevalent somatosensory symptom that can be highly disabling, because it is likely to draw attention and, as a result, may interfere with the performance of daily activities. Yet,... Show moreItch is a prevalent somatosensory symptom that can be highly disabling, because it is likely to draw attention and, as a result, may interfere with the performance of daily activities. Yet, research experimentally investigating attention to itch is lacking. In this study we aimed to investigate attentional processing of itch using multiple behavioral attention tasks. Forty-one healthy participants performed (1) a modified Stroop task with itch-related words, (2) a dot-probe task with itch-related pictures, and (3) a recently developed somatosensory attention task in which the effect of experimentally induced itch on the localization of visual targets was examined. Additionally, a number of self-report questionnaires related to somatosensory attentional processing were administered. Results indicated that participants’ attention was biased toward itch-related words and pictures assessed by means of the dot-probe and modified Stroop task, respectively. For the somatosensory attention task, results showed that itch did not significantly influence the allocation of attention. However, when taking into account the time course of attention during the itch stimulus, data suggested that participants tended to disengage attention away during the itch stimulus. This is the first study that indicates an attentional bias for itch, using methods that have previously been validated for other sensations such as pain. In addition, the newly developed somatosensory attention task may reflect the time course of attention toward a tonic itch stimulus. Show less
Meeuwis, S.H.; Middendorp, H. van; Veldhuijzen, D.S.; Laarhoven, A.I.M. van; De Houwer, J.; Lavrijsen, A.P.M.; Evers, A.W.M. 2018
Placebo effects are positive outcomes that are not due to active treatment components, which may be elicited even when patients are aware of receiving an inert substance (open-label). This proof-of... Show morePlacebo effects are positive outcomes that are not due to active treatment components, which may be elicited even when patients are aware of receiving an inert substance (open-label). This proof-of-principle study investigated for the first time whether open-label placebo effects on itch can be induced by verbal suggestions alone. Ninety-two healthy volunteers were randomized to experimental (open-label suggestions) or control (no suggestions) groups. Self-reported itch evoked by histamine iontophoresis was the primary study outcome. In addition, itch expectations, skin condition and affect were assessed. The experimental group expected lower itch than the control group, which was, in turn, related to less experienced itch in this group only, although no significantly different itch levels were reported between groups. The results illustrate a potential role for open-label placebo effects in itch, and suggest that further study of verbal suggestions through an extensive explanation of placebo effects might be promising for clinical practice. Show less
Nocebo effects, i.e. reduced treatment effects due to patients’ negative expectations, play a role in itch. Recent studies have shown that nocebo effects can be induced experimentally on itch and... Show moreNocebo effects, i.e. reduced treatment effects due to patients’ negative expectations, play a role in itch. Recent studies have shown that nocebo effects can be induced experimentally on itch and also be minimized and even turned into the opposite direction, i.e. placebo effects. It is not known whether these effects generalize to itch-associated scratching behaviour. The aim of this study was to determine whether induction and reversal of nocebo effects on itch evoked by electrical and histamine stimuli generalized to scratching. Ninety-seven healthy participants were included in the study. The manipulation was successful, as during the nocebo learning phase, increased scratching responses were found for higher intensity compared with lower intensity itch stimuli. During the testing phase of induction or reversal of the nocebo effects, however, no significant nocebo effects or reversed nocebo effects, were found in scratching. Thus, no straightforward generalization of nocebo effects from itch to scratching was found in this laboratory setting. Further investigation into possible generalization is needed in different settings and in patients with chronic itch. Show less
