Analgesic and Antihyperalgesic Effects of Morphine and Buprenorphine

Study Overview
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Brief Summary
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Tissue injury is associated with pain from the injured site (primary hyperalgesia) and pain from non-injured tissue in the vicinity of the trauma (secondary hyperalgesia). In the present study we investigate primary and secondary hyperalgesia in healthy volunteers following an experimental first degree burn injury. The objectives are: to compare analgesic and anti-hyperalgesic effects of two opioids (morphine and buprenorphine). to investigate if these effects are related to the volunteers individual pain sensitivity

Detailed Description
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Please refer to: Ravn P, Secher EL, Skram U, Therkildsen T, Christrup LL, Werner MU (2013) Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study. J Pain Res 6: 23-38. 10.2147/JPR.S36827 [doi];jpr-6-023 [pii].

Official Title
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Analgesic and Antihyperalgesic Effects of Morphine and Buprenorphine Following an Experimental Inflammatory Injury in Volunteers.

Conditions
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Pain

Intervention / Treatment
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* Drug: morphine LO
* Drug: Morphine Hi
* Drug: Buprenorphine LO
* Drug: Buprenorphine Hi
* Other: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy individuals adequate psychomotor performance to perform pain tests pain-sensitive or pain-nonsensitive according to prespecified criteria Exclusion Criteria: known allergy to morphine or buprenorphine prior adverse experiences with opioids history of abuse females not taking P-pills skin lesions on the test-sites suffering from chronic pain medication with analgesics BMI > 28 smoker

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: morphine low dose<br>morphine infusion 10 mg over a 210 min period | Drug: morphine LO<br>* intravenous infusion, 10 mg, once, 4 hours<br>* Other names: Morfin SAD;|
| Experimental: morphine high dose<br>morphine infusion 20 mg over a 210 min period | Drug: Morphine Hi<br>* intravenous infusion, 20 mg, once, 4 hours<br>* Other names: Morfin SAD;|
| Experimental: buprenorphine low dose<br>buprenorphine infusion 0.3 mg over a 210 min period | Drug: Buprenorphine LO<br>* intravenous infusion, 0.3 mg, once, 4 hours<br>* Other names: Temgesic;|
| Experimental: buprenorphine high dose<br>buprenorphine infusion 0.6 mg over a 210 min period | Drug: Buprenorphine Hi<br>* intravenous infusion, 0.6 mg, once, 4 hours<br>* Other names: Temgesic;|
| Placebo Comparator: placebo<br>placebo (normal saline) infusion 0.6 mg over a 210 min period | Other: saline<br>* intravenous infusion, 0.9% saline, once, 4 hours<br>* Other names: 0.9% NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analgesic and antihyperalgesic effects | Analgesic effect is assessed by change in primary hyperalgesia (pain rating [VAS]) Antihyperalgesic effect is assessed by reduction in area of hyperalgesia (sq. cm) VAS-area under curve is calculated for 0, 60, 120 and 180 min after first degree burn injury | 0 to 180 min after a first degree burn injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in analgesic/antihyperalgesic profile between pain-sensitive and pain-non-sensitive individuals | The ratios between areas under curve (0-180 min after first degree burn injury) for analgesic effect assessed by change in primary hyperalgesia (pain rating VAS])and antihyperalgesic effect assessed by reduction in area of hyperalgesia (sq. cm). | 0-180 min after first degree burn injury | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioids, analgesia, secondary hyperalgesia, quantitative sensory testing, inflammatory injury