Morphine, Itch
Conditions
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.
Interventions
DRUGMorphine
A 20 mg tablet of morphine
DRUGPlacebo oral tablet
Matching tablet of placebo
DRUGHistamine
Histaminergic itch will be evoked by a 1% histamine solution. A droplet of histamine solution will be placed on the predetermined area on the forearm, and the SPT lancet will be pierced through the histamine with 120 g of pressure for 1-2 seconds.
25 spicules will be inserted in the centre of the predefined skin area on the forearm. The spicules will be gently rubbed for 15-20 seconds in circular motion to facilitate epidermal penetration
DRUGisotonic saline
A droplet of saline (0.9%) as vehicle control will be placed on the predetermined area on the forearm and the lancet will be pierced through the droplet.
Sponsors
Aalborg University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women in the age of 20-65 years * The participants must be able to 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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microvascular reactivity | Before and 70 minutes after morphine/placebo administration | 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
| Measure | Time frame | Description |
|---|---|---|
| Cold (CPT) and heat (HPT) pain thesholds | 10 minutes before 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 | 10 minutes before 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. |
Countries
Denmark
Outcome results
None listed