651: Placebo Effects on Histaminergic and Non-Histaminergic Itch: Interplay with Psychological Factors

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Itch, Psychology, Placebo/Nocebo

Background and Aims: Chronic itch represents a common yet underestimated public health problem due to its prevalence of ~20%, the negative impact on quality of life and the lack of optimal treatments. According to the biopsychosocial model, internal and external factors are involved in itch perception 1. Although placebo effect is well established in pain treatment, little is known about this phenomenon in chronic itch 2. Evidence suggests placebo can improve pruritus, overall symptoms, and quality of life in chronic itch conditions 3.
This study aimed to evaluate the placebo effect on itch perception in healthy volunteers and its relationship with psychological factors.

Methods: Twenty-six healthy subjects were recruited for this study. The participants completed questionnaires about helplessness (Learned Helplessness Scale - LHS), and emotional regulation (Difficulties in Emotion Regulation Scale Short Form - DERS-SF, and Emotion Regulation Questionnaire - ERQ). Two 4×4 cm areas were marked on each forearm. All areas were treated with the same vehicle cream for 20 minutes, but participants were instructed that two areas contain “active cream” and two contain “vehicle”. Afterwards, two areas received histamine and the other two cowhage. Itch was continuously recorded on a VAS during the 10-minute pruritogen application.

Results: Histamine- and cowhage-induced itch peak intensity and area under the curve (AUC) induced were lower after pretreatment with “active cream” compared to “vehicle” (p<0.001). The effect on histamine-induced peak intensity was 30.77% (Cohen’s D=0.57), while it was 19.11% (D=0.52) for cowhage. AUC of histamine decreased by 33.50% (D=0.50), while cowhage by 20.92% (D=0.53). Negative correlations were found between cowhage-AUC after vehicle and ERQ (r=-0.393, p<0.05), specifically for the emotion suppression component (r=-0.511, p<0.01). Regarding the placebo effect, the reduction of histaminergic itch was negatively correlated with LHS (peak: r=-0590, AUC: r=-0.504, p<0.01).

Conclusions: This study demonstrates that placebo treatment significantly reduces experimentally induced both histaminergic and non-histaminergic itch in healthy volunteers. The magnitude of the placebo effect, comparable of what has been found for pain, was influenced by psychological factors, with higher helplessness associated with smaller reductions in histamine-induced itch. Psychological factors were also associated with the perception of non-histaminergic itch, with higher emotion regulation linked to lower cowhage-induced itch.
These findings highlight the role of psychological factors in itch and suggest that leveraging placebo mechanisms could improve symptom management and quality of life in chronic itch patients alongside standard treatments.

References: 1. Verhoeven EWM, Klerk S de, Kraaimaat FW, Van de Kerkhof PCM, De Jong EMGJ, Evers AWM. Biopsychosocial mechanisms of chronic itch in patients with skin diseases: a review. Published online 2008.
2. van Laarhoven AIM, van der Sman-Mauriks IM, Donders ART, Pronk MC, van de Kerkhof PCM, Evers AWM. Placebo effects on itch: a meta-analysis of clinical trials of patients with dermatological conditions. J Invest Dermatol. 2015 May;135(5):1234-1243. doi: 10.1038/jid.2014.522. Epub 2014 Dec 1. PMID: 25609025.
3. Xue, P., Qin, H., Qin, D. et al. The Effect of Placebo on Pruritus in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Clin Drug Investig 44, 635–654 (2024). https://doi.org/10.1007/s40261-024-01389-5

Presenting Author: Giulia Erica Aliotta
Submitting Author: Giulia Erica Aliotta

Senior Author: Silvia Lo Vecchio

IASP 2026 Global Year theme of Neuropathic Pain: No

• Niccoló Paladini - Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Universitá degli Studi di Milano, Milan, Italy and CNAP, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark
• Benedetta Riboldi: MSc - Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Universitá degli Studi di Milano, Milan, Italy and CNAP, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark
• Jesper Elberling: PhD - Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Denmark and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
• Lars Arendt-Nielsen: PhD - CNAP, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark and Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark and Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark
• Laura Petrini: PhD - CNAP, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark
• Stefania Ceruti: PhD - Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Universitá degli Studi di Milano, Milan, Italy
• Silvia Lo Vecchio: PhD - CNAP, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark