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The aim of the current project is to use a model of painful stimulation of skin, muscles and internal organs, where it is possible to measure activity in the brain centers that process pain simultaneously. Magnetic resonance imaging and electroencephalography are combined to optimize the anatomical and physiological description of brain activation. During administration of morphine we will identify how different brain areas are affected. This knowledge will be used to:
1. Understand the mechanisms of morphine to a greater extent than is possible today, including:
The tests will consist of one main study (I) and one sub-study (i):
I) Experiments in the painlaboratory in the gastroenterology clinic, where 40 healthy subjects will be examined with different pain tests i) Experiments in the MRI scanner, where only 20 of the 40 from the main study will be investigated in a more simple pain model. The individuals who also participate in MRI studies, will consist of those who first sign up
An equal distribution of men and women is wanted. The trial will be a double-blind, placebo-controlled crossover study in which all subjects will be investigated on two seperate days and receive respectively placebo or morphine in random order
Skin stimulation
Skin will be stimulated with thermal and electrical stimuli. Stimulated by:
Muscle stimulation
The muscles can be stimulated by:
• mechanical stimuli by pressing the muscle with an approved pressure algometer (Somedic produktion AB, Sweden). There is an upper limit for the pressure to avoid injury.
Bone stimulation
Bone associated pain can be studied by:
• mechanical stimuli by pressing the right shin bone 15cm below the patella, medial of the tibia. Pressed with a handheld trykalgometer (Type 2, Somedic produktion AB, Sweden) with a probe size of 2mm in diameter until trial participants reach their pain tolerance threshold.
Visceral stimuli Stimuli to the rectum will be performed through the probe specifically designed for this purpose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Morphine | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Morphine | Drug | Morphine oral mixture |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Morphine modulation of composite pain assessments | october 2010 - december 2012 |
| Measure | Description | Time Frame |
|---|---|---|
| Side effects of morphine | october 2010 - december 2012 |
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Inclusion Criteria:
Signed and dated "Written informed consent"
Age between 20 and 65.
Caucasian
That it is in the researcher's belief that the subject fully understand the contents of the study and is willing and able to comply with instructions, have the opportunity to meet with visitors, and is expected to complete the entire study. Further, it is in the researcher's beliefs (by which demanded strict action to exclusion criterion 4 and 5) that subjects with abusive tendencies are not included .
The person must be healthy ie. without previous chronic or recurrent pain rewarding diseases. Including the person must have:
That women use safe contraceptive methods as the pill, coil, depot injection of progestin subdermal implantation, hormonal vaginal ring and transdermal patch.
Negative pregnancy test prior to the conclusion of the experiment
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne E Olesen, PhD | Aalborg University Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Gastroenterology, Aalborg Hospital | Aalborg | 9000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25924691 | Derived | Hansen TM, Olesen AE, Graversen C, Drewes AM, Frokjaer JB. The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study. Basic Clin Pharmacol Toxicol. 2015 Nov;117(5):316-22. doi: 10.1111/bcpt.12415. Epub 2015 May 29. | |
| 25556985 | Derived | Hansen TM, Graversen C, Frokjaer JB, Olesen AE, Valeriani M, Drewes AM. Single-sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment. Br J Clin Pharmacol. 2015 Jun;79(6):926-36. doi: 10.1111/bcp.12579. |
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| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D009020 | Morphine |
| ID | Term |
|---|---|
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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| orange juice | Other | orange juice |
|
|
| 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 |