The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients.
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 vs 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.
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|Department of Radiology, Logan University, Chesterfield, MO, USA.
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V
Napadow
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
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A
Li
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
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Loggia
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
J
J
Kim
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
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I
Mawla
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
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G
Desbordes
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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PC
Schalock
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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EA
Lerner
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Tran
Department of Dermatology and Allergy, Technische Universität München, Munich, Germany.
J
J
Ring
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
B R
BR
Rosen
Program in Placebo Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
T J
TJ
Kaptchuk
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.|Department of Dermatology and Allergy, Technische Universität München, Munich, Germany.|Department of Prevention and Sports Medicine, Technische Universität München, Munich, Germany.
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Pfab
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D001921:Brain / Q000503:physiopathology*; D003876:Dermatitis, Atopic / Q000175:diagnosis* / Q000523:psychology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D064786:Nocebo Effect; D011537:Pruritus / Q000175:diagnosis / Q000523:psychology*; D012882:Skin Tests; D055815:Young Adult
D000485:Allergens
atopic dermatitis; caudate; nocebo; placebo; pruritus