The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients

Abstract

Background Psychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. Methods We collected functional MRI (fMRI) data from atopic dermatitis (AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen versus open-label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. Results Nocebo saline produced greater itch than open saline control (p<0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dlPFC), and intraparietal sulcus (iPS) - brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dlPFC and caudate activation to nocebo-induced itch also demonstrated greater dlPFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen-evoked itch, suggesting increased generalized modulation of itch perception. Conclusions Our study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients.

Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible

“…Apart from such neuroendocrineimmunological mechanisms, the brain modulates skin sensations also by emotional and cognitive aspects. For example, itch stimuli may be perceived diminished [11] by distraction or enhanced by negative suggestion [12] or in depression. [13] Further evidence for the skin-brain connection includes various neurocutaneous conditions such as phakomatoses [14][15][16][17] and the large field of psychodermatology.…”

“…To date, itch has been studied using fMRI in a small number of patients with atopic dermatitis (AD), [12,[82][83][84][85][86][87] lichen simplex chronicus, [88] prurigo nodularis, [88] end-stage renal disease [89] and psoriasis. [82] Most of these studies were within-subject and placebo-controlled but without direct comparison to healthy controls.…”

“…[78] Placebo effects have not as yet been specifically addressed through fMRI; however, one study reported that nocebo-saline was perceived to be more itchy than open saline and produced a greater response in itch-processing brain regions. [12] Evidence from several non-imaging studies indicates that patients with AD and other chronic itch conditions are particularly susceptible to placebo effects and nocebo effects. [95] Whereas nocebo effects seem to be correlated with individual characteristics, distress, worrying and neuroticism, almost no correlation between these characteristics and placebo were found.…”

Placebo and nocebo effects on itch: effects, mechanisms, and predictors

“…One of the first studies on verbal suggestion and itch found that patients with AD reported more itch and had a stronger skin response to a topical histamine application when exaggerated verbal suggestions were given, than when downplayed suggestions were given (Scholz and Hermanns, 1994). Further evidence for the role of verbal suggestion in nocebo effects on itch comes from a study investigating the neurobiology of nocebo effects in patients with AD (Napadow et al, 2013). Participants who were told that 95% of the healthy people experience itch from the stimuli to be applied reported significantly higher levels of evoked itch than those who were told that only 5% of the healthy people experience itch from the stimuli.…”

Single‐use IgE‐selective immunoadsorber column for the treatment of severe atopic dermatitis

“…In addition, based on the vascular status of our probands, IA in this study could be performed using just peripheral instead of central venous catheters, the latter which harbor an increased risk for Staphylococcus aureus septicemia 12,16 or air embolism. [22][23][24] Likewise, seasonal variations of AD severity could have had an impact on SCORAD as an outcome measure. 13 One major limitation of this pilot study is the absence of a placebo control.…”