Mechanisms Underlying the Placebo Effect in Both Histaminergic and Non-histaminergic Itch

Pain and Itch Neuromodulation: Effects of Offset Analgesia, Placebo, and Nocebo and Topographical Distribution of Itch and Pain Receptors

The study consists of one experimental session of approximately 1½ hours. The participant will fill in a series of questionnaires about how you perceive itch and pain, and about some traits of your personality, such as depression, anxiety and stress. Afterwards, two areas will be selected on each forearm of the subjects. The four areas will be treated with the same vehicle cream for 20 minutes, in order to test the placebo effect. At the end of the cream application, two areas will be randomly treated with histamine while cowhage will be applied on the other two areas. During the 10 minutes of the application of the pruritogens, itch and pain will be continuously monitored using a Visual Analog Scale.

Study Overview

• Status: Recruiting
• Conditions: ITCH
• Intervention / Treatment: Other: Histamine; Other: Cowhage

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Silvia Lo Vecchio; Phone Number: +4521397785; Email: slv@hst.aau.dk

Study Locations

• Denmark
  • Gistrup, Denmark, 9260
    • Recruiting
    • Aalborg University
    • Contact: Silvia Lo Vecchio, PhD; Phone Number: Denmark; Email: slv@hst.aau.dk
    • Contact: Phone Number: Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy men and women
• 18-60 years
• Speak and understand English

Exclusion Criteria:

• Pregnancy or lactation
• Drug addiction defined as any use of cannabis, opioids, or other drugs
• Previous or current history of neurological, immunological, musculoskeletal, cardiac disorder or psychiatric diagnoses that may affect the results (e.g., neuropathy, muscular pain in the upper extremities, anxiety, depression, schizophrenia, etc.)
• Moles, wounds, scars, or tattoos in the area to be treated or tested
• Current use of medications that may affect the trial such as antihistamines and pain killers
• Skin diseases
• Consumption of alcohol or painkillers 24 hours before the study days and between these
• Acute or chronic pain and itch
• Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical studies)
• Contraindications to capsaicin, including intolerance to chili or burns or wounds at the application site
• The subject is assessed as unable to engage in the necessary cooperation required by the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; A placebo cream (Pentravan cream) will be applied on the volar forearm for 20 minutes.	Other: Histamine; To deliver histamine, standard allergy skin prick test (SPT) lancets are applied; Other: Cowhage; The spicules will be manually inserted. Approximately 30-35 spicules are gently rubbed into a 1 cm diameter skin area on the forearm/face

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring pain by computerized Visual Analog Scale Scoring	We will ask the subjects to rate the sensation of pain on a 100 mm Visual Analog Scale ranging from 0 to 100 where 0 indicates" no pain" and 100 indicates "worst pain imaginable".	Immediately after the intervention
Measuring itch by computerized Visual Analog Scale Scoring	We will ask the subjects to rate the sensation of itch on a 100 mm Visual Analog Scale ranging from 0 to 100 where 0 indicates "no itch" and 100 indicates "worst itch imaginable".	Immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Learned Helplessness Scale (LHS)	The questionnaire consists of 20 items, and the participant's response to each item is rated on a 4-point Likert scale ranging from strongly agree (1) to strongly disagree (4).	Baseline
Pain Catastrophizing Scale (PCS).	The PCS assesses negative and exaggerated coping concerning anticipated or experienced painful stimuli. Thirteen items have to be answered on a 5-point Likert-type scale ranging from 0 (Not at all) to 4 (all the time).	Baseline
Itch Catastrophizing Scale (ICS).	The ICS assesses negative and exaggerated coping concerning anticipated or experienced itchy stimuli. Thirteen items have to be answered on a 5-point Likert-type scale ranging from 0 (Not at all) to 4 (all the time).	Baseline
Depression, Anxiety, Stress Scale (DASS-21)	The questionnaire measures the magnitude of depression, anxiety, and stress. Each of these three subscales consists of 7 questions answered using a 0-3 Likert scale, with 0 meaning "it did not apply to me", and 3 meaning "it applied to me very much"	Baseline
Difficulties in Emotion Regulation Scale Short Form (DERS-SF)	The questionnaire is an 18-item measure used to identify emotional regulation issues in adults. Participants rate each item on a 5-point Likert scale (from 1 to 5).	Baseline
Emotion Regulation Questionnaire (ERQ	This questionnaire is designed to assess individual differences in the habitual use of two emotion regulation strategies: cognitive reappraisal and expressive suppression. Respondents answer each item on a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree), where 4 means (neutral).	Baseline
Reinforcement Sensitivity Theory - Personality Questionnaire (RST-PQ).	The RST-PQ contains in total 65 items must be answered on a Response scale: 4-point Likert (Strongly disagree → Strongly agree).	Baseline
Positive And Negative Affect Schedule (PANAS)	Twenty words are associated with the subject's current feelings and have to be rated on a 5-points Likert-type scale from: Very slightly or not at all to extremely.	Baseline

Collaborators and Investigators

• Sponsor: Aalborg University
• Investigators: Principal Investigator: Silvia Lo Vecchio, Aalborg Universitet

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Estimated): November 25, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Biological Factors; Imidazoles; Amines; Ethylamines; Autacoids; Inflammation Mediators; Biogenic Monoamines; Biogenic Amines; Histamine
• Other Study ID Numbers: N-20250017 Project 2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No