A Relation of Morphine-induced Itch and Pain Processing
- Conditions
- ItchMorphine
- Interventions
- Drug: Placebo oral tabletDrug: Cowhage (Mucuna Pruriens)Drug: isotonic saline
- Registration Number
- NCT04115462
- Lead Sponsor
- Aalborg University
- Brief Summary
In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:
1. Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).
2. Opioids cause itch through a mast cell-destabilizing effect leading to release of histamine and tryptase in the skin where itch is evoked (peripheral mechanism).
- Detailed Description
Intrathecal and orally administered opioids are heavily used for the treatment of several acute pain conditions. However, while opioids are effective analgesics for acute pain, they are well-known to frequently cause itch (pruritus) as a side effect according with the two hypotheses stated above. So far, these two hypotheses have never been tested in humans.The present study describes a proposed study design for the purpose of confirming these two hypotheses in parallel in human subjects.
Primary endpoints of the study:
To evaluate changes itch and pain perception, and superficial perfusion after each itch provocations.
Secondary endpoints of the study:
To evaluate the existence of a correlation between itch sensitization and analgesic efficacy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- Healthy men and women in the age of 20-65 years
- The participants must be able to speak and understand English
- 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.
- Pregnant or lactating female persons
- Drug addiction defined as the use of cannabis, opioids or other drugs
- Previous or present neurologic, musculoskeletal or mental illnesses
- Current pain and itch causing diseases or psychiatric disorders
- Participants unable to understand or follow the instructions
- Participating in another study where investigational drug is used
- Participants had known allergy/discomfort to morphine
- Lack of ability to cooperate
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo oral tablet Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Placebo Cowhage (Mucuna Pruriens) Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Morphine isotonic saline Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Morphine Cowhage (Mucuna Pruriens) Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Placebo isotonic saline Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Morphine Morphine Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Morphine Histamine Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations. Placebo Histamine Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.
- Primary Outcome Measures
Name Time Method Microvascular reactivity 10 minutes after every itch inductions The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.
Assessment of itch 1 minute after every itch inductions 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 1 minute after every itch inductions 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
Name Time Method Cold (CPT) and heat (HPT) pain thesholds 60 minutes after morphine/placebo administration Thermal cold and heat stimuli will be applied by a contact heat-evoked potential stimulator (PATHWAYS; Medoc Ltd, Ramat Yishai, Israel), placed 5 cm distal to the elbow on the right dorsal forearm.
Pressure Pain Threshold 60 minutes after morphine/placebo administration Pressure will be applied to the supinator muscle on the left forearm, 15 cm distal to the elbow by a handheld electronic pressure algometer (Somedic AB, Stockholm, Sweden) with a standard probe of 1 cm2.
Trial Locations
- Locations (1)
Mech-Sense, Medicinsk Gastroenterologisk ambulatorium, Medicineshus, Aalborg Universitetshospitalet,
🇩🇰AAlborg, Nordjylland, Denmark