Evaluation of Peripheral Itch Mechanisms Following Injection of Morphine (Second Sub-Project)

Effect of Intradermal Morphine Application on Histaminergic and Non-histaminergic Itch and Related TRPV1 and Antihistamine Treatments (2nd Sub-project)

The aim of our 2nd sub-project is to clarify if the capsaicin receptor TRPV1 is implicated in the mechanism of morphine-induced mast cell degranulation. Moreover, we also aim to clarify if the mechanism of opioid-induced itch relay on the histaminergic pathway by using the antihistamine (diphenhydramine) to suppress the release of histamine from peripheral mast cells.

Study Overview

• Status: Completed
• Conditions: Itch
• Intervention / Treatment: Drug: Capsaicin; Drug: Diphenhydramine; Drug: Morphine Chloride; Drug: Isotonic saline; Drug: Histamine

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Nordjylland
    • AAlborg, Nordjylland, Denmark, 9000
      • Mech-Sense, Medicinsk Gastroenterologisk ambulatorium, Medicineshus, Aalborn Universitethospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Participants with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
• Pregnancy or lactation
• Drug addiction defined as any use of cannabis, opioids or other addictive drugs
• 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.
• Participants with known allergy/discomfort to the opioid morphine and antihistamine.
• Skin diseases
• 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 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Study group

Drug: Capsaicin; A capsaicin patch will be applied on a 3x3 cm squared area on the volar forearm. The patch will be left in place for 24h after which it will be removed.; Drug: Diphenhydramine; Diphenhydramin cream 1% (Restamine®) will be applied on a 3x3 cm squared predetermined area on the volar forearm for 24 hours.; Other Names: Antihistamine; Drug: Morphine Chloride; Morphine solution (0.1mg/ml, Morphine Hydrochloride) 50 μl will be applied intradermally to the center of a predetermined area on the volar forearm by a 1 ml syringe.; Drug: Isotonic saline; injections of isotonic saline (0.05 ml, 0.9%) as vehicle will be performed.; Drug: Histamine; A small drop of histamine dihydrochloride (1%, in saline) will be applied to a previously determined area on the volar forearm followed by a prick through the drop.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring itch intensity by computerized Visual Analog Scale Scoring	We will ask the subjects to rate the sensation of itch on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates "no itch" and 100 indicates "worst itch imaginable".	For 10 minutes
Measuring pain intensity by computerized Visual Analog Scale Scoring	We will ask the subjects to rate the sensation of pain on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates "no pain" and 100 indicates "worst pain imaginable".	For 10 minutes
Superficial blood perfusion measurement	Superficial blood perfusion is measured by a Speckle contrast imager	After 15 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
While size	While size will be assessed using a ruler	After 15 minutes

Collaborators and Investigators

• Sponsor: Aalborg University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 18, 2021
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): December 31, 2021

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (ACTUAL): January 7, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 26, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Agents; Antipruritics; Histamine Agonists; Diphenhydramine; Promethazine; Morphine; Capsaicin; Histamine Antagonists; Histamine
• Other Study ID Numbers: N-20200084 2nd sub-project

Drug and device information, study documents

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