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Repetitive Applications of Pruritogens and Effects of a Cutaneous-induced Pain Stimulation on Nonhistaminergic Itch Perception

Not Applicable
Active, not recruiting
Conditions
Cowhage
Histamine
Interventions
Other: Cowhage
Other: Histamine
Registration Number
NCT06154824
Lead Sponsor
Aalborg University
Brief Summary

In This experiment, the investigators would like to test following hypotheses:

repetitive cutaneous administration of pruritogens will lead to a more robust and longer lasting itch sensation compared with a single application. The aim of this project is to investigate a new itch model based on repetitive administration of three different pruritogens: histamine (histaminergic itch), cowhage, and BAM 8-22 (non-histaminergic itch).

Detailed Description

Chronic itch affects approximately a fifth of the global population and is associated with substantial negative consequences for the affected individuals. Furthermore, there is a lack of efficient treatment options for chronic itch. In order to mimic a clinical itch condition as presented in patients, the aim of the project is to investigate a new itch model based on repetitive administration of three different pruritogens: histamine (histaminergic itch), cowhage, and BAM 8-22 (non-histaminergic itch). The hypothesis is that repetitive cutaneous administration of pruritogens will lead to a more robust and longer-lasting itch sensation compared with a single application. This proposal for a new itch model could better mimic clinical itch conditions and be used to investigate fundamental mechanisms, new anti-pruritic drugs, and their possible mechanisms of action.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
30
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 addictive drugs
  • Previous or current history of neurological (e.g. neuropathy), immunological (e.g. asthma, immune deficiencies, arthritis) musculoskeletal (e.g. muscular pain in the upper extremities,), cardiac disorder, or mental illnesses that may affect the results
  • Lack of ability to cooperate
  • Current use of medications that may affect the trial such as antihistamines, antipsychotics, and pain killers, as well as systemic or topical steroids
  • Skin diseases (e.g. atopic dermatitis, pruritus nodularis, eczema, psoriasis)
  • Moles, scars, or tattoos in the area to be treated or tested.
  • Consumption of alcohol or painkillers 24 hours before the study days and between these
  • Acute or chronic pain
  • Participation in other trials within one week of study entry (four weeks in the case of pharmaceutical trials)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1st pruritogenCowhageThe study takes place over two sessions over a period of 7 days. The duration of the sessions is approx. 4 hours in total. In the 1st session, a squared area of 4x4 cm will be selected at the center of each middle forearm of the subject. The two areas will be randomly treated with one of the following substances: cowhage, histamine, BAM 8-22 or vehicle. Each substance will be applied for 10 minutes, during which the pain/itch following the substance application will be monitored. Twenty minutes after each application, the measurements with FLPI will be conducted. Then the measurements of alloknesis and mechanically evoked itch, will be conducted. This procedure will be repeated three times for each substance; so in total each substance will be applied three times, each application lasting 10 minutes.
2nd pruritogenHistamineThe study takes place over two sessions over a period of 7 days. The duration of the sessions is approx. 4 hours in total. In the 1st session, a squared area of 4x4 cm will be selected at the center of each middle forearm of the subject. The two areas will be randomly treated with one of the following substances: cowhage, histamine, BAM 8-22 or vehicle. Each substance will be applied for 10 minutes, during which the pain/itch following the substance application will be monitored. Twenty minutes after each application, the measurements with FLPI will be conducted. Then the measurements of alloknesis and mechanically evoked itch, will be conducted. This procedure will be repeated three times for each substance; so in total each substance will be applied three times, each application lasting 10 minutes.
Primary Outcome Measures
NameTimeMethod
Assessment of itch intensity1 minute post itch provocation

Immediately following the itch provocations, participants will be instructed to rate the itch intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no itch' and 100 'worst itch imaginable'.

Assessment of pain intensity1 minute post itch provocation

Immediately following the itch provocations, participants will be instructed to rate the pain intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no pain' and 100 'worst pain imaginable'.

Secondary Outcome Measures
NameTimeMethod
Alloknesis12 minutes post itch provocation

Alloknesis sensation is measured using a standardized sensory brush (SENSELab Brush-05, Somedic AB, Hörby, Sweden) exerting a force of 200 to 400 mN.

Superficial blood perfusion10 minutes post itch provocation

The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.

Mechanically evoked itch15 minutes post itch provocation

Mechanically evoked itch is measured using three von Frey filaments of 4.08, 4.16 and 4.31 (1.0, 1.4, 2.0 g, respectively) (North Coast Medical, Gilroy, CA). The center of the skin area is stimulated by 3 pricks, repeated 3 times in short succession. After a total of 9 stimulations, the participants will report the itch elicited on a numerical rating scale (NRS) from 0 to 10 (0 = "no itch"; 10 = "worst imaginable itch").

Trial Locations

Locations (1)

Aalborg University

🇩🇰

Aalborg, Denmark

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