Influence of Propranolol on Conditioned Pain Modulation

Study Overview
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Brief Summary
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An extensive amount of studies indicate that conditioned pain modulation (CPM) test paradigms can be of use to evaluate the efficacy of the endogenous pain inhibition pathway in healthy controls and pain patients. A number of studies indicate that the autonomic nervous system (ANS) responds to painful stimulation by parasympathetic activity withdrawal and up-regulation of sympathetic activity (flight-or-fight mode), but it remains unknown whether these responses predict individual pain susceptibility or CPM efficacy and whether different pain modalities evoke different physiological stress responses, i.e. do individuals with low pain tolerance exhibit more vigorous ANS responses when subjected to controlled acute pain stimuli, and do high ANS responsiveness to pain coincide with altered psychophysical pain levels/CPM efficacy. This study aims to investigate the effect of ANS responsiveness on CPM paradigms and to investigate if an exogenous, pharmaceutically induced decrease in the sympathetic drive of the ANS will yield decreased CPM efficacy.

Official Title
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Konditionerende Smertestimuli - Sammenligning af Forskellige Test og Konditioneringsmodaliteter

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: propranolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects Exclusion Criteria: Drug addiction defined as the use of cannabis, opioids or other drugs Previous history of neurologic, musculoskeletal, mental illnesses or a chronic pain condition Lack of ability to cooperate Current use of medications that may affect the trial, e.g., analgesics, anti-inflammatory drugs Consumption of alcohol, caffeine, nicotine or painkillers the morning and until termination of the study on the study day Recent history of acute pain affecting the lower limb Participation in other pain trials throughout the study period Known diagnosis of cardio vascular diseases (low blood pressure, heart conditions) Asthma Decreased function of liver and kidneys Diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propranolol<br>Propranolol is a beta-blocker | Drug: propranolol<br>* Reduction of the ANS response<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CPM efficacy | A test stimuli will be applied and compared with a test stimuli simultaneous a condition stimuli. | 1-2 hours after propranolol/placebo and after 10 minutes break. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temporal summation of pain | 10 stimuli will be applied and subjects will back asked to rate the pain for each individual stimuli. | 1-2 hours after propranolol/placebo and after 10 minutes break. | 
| Heart-rate variability | Two-point Heart-rate variability recording will be conducted using the Polar RS800CX heart rate monitor. | 1-2 hours after propranolol/placebo and after 10 minutes break. | 
| Offset analgesia | Temperatures ranging from 45-48°C will be applied to the forearm in three phases (phase 1: 5 seconds, phase 2: 5 seconds, and phase 3: 20 seconds). The subjects will be asked to assess the pain of the thermal stimuli using the electronic VAS scale. | 1-2 hours after propranolol/placebo and after 10 minutes break. |