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In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Morphine | Active Comparator | 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 | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Morphine | Drug | A 20 mg tablet of morphine |
| |
| Placebo oral tablet |
| Measure | Description | Time Frame |
|---|---|---|
| Microvascular reactivity | The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging. | Before and 70 minutes after morphine/placebo administration |
| Microvascular reactivity | The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging. | 10 minutes after every itch inductions |
| Assessment of itch | 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'. | 1 minute after every itch inductions |
| Assessment of pain | 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'. | 1 minute after every itch inductions |
| Measure | Description | Time Frame |
|---|---|---|
| Cold (CPT) and heat (HPT) pain thesholds | 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. | 10 minutes before morphine/placebo administration |
| Cold (CPT) and heat (HPT) pain thesholds |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mech-Sense, Medicinsk Gastroenterologisk ambulatorium, Medicineshus, Aalborg Universitetshospitalet, | Aalborg | North Denmark | 9000 | Denmark |
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| ID | Term |
|---|---|
| D011537 | Pruritus |
| ID | Term |
|---|---|
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D009020 | Morphine |
| D006632 | Histamine |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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| Drug |
Matching tablet of placebo |
|
| Histamine | Drug | 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. |
|
| Cowhage (Mucuna Pruriens) | Drug | 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 |
|
| isotonic saline | Drug | 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. |
|
|
| Histamine | Drug | Histaminergic itch will be evoked by a 1% histamine solution. A droplet of histamine solution will be placed on the predetermined area on the mandibular area, and the SPT lancet will be pierced through the histamine with 120 g of pressure for 1-2 seconds. |
|
| Cowhage (Mucuna Pruriens) | Drug | 25 spicules will be inserted in the centre of the predefined skin area on the mandibular area. The spicules will be gently rubbed for 15-20 seconds in circular motion to facilitate epidermal penetration |
|
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. |
| 60 minutes after morphine/placebo administration |
| Pressure Pain Threshold | 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. | 10 minutes before morphine/placebo administration |
| Pressure Pain Threshold | 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. | 60 minutes after morphine/placebo administration |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D005021 | Ethylamines |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |