Influence of Propranolol on Conditioned Pain Modulation

Konditionerende Smertestimuli - Sammenligning af Forskellige Test og Konditioneringsmodaliteter

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: propranolol

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg East, Denmark, 9220
    • Center for Sensory Motor Interaction, Aalborg University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Active Comparator: Propranolol; Propranolol is a beta-blocker	Drug: propranolol; Reduction of the ANS response

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Kristian Kjær Petersen
• Investigators: Principal Investigator: KRISTIAN K PETERSEN, Ph.D., Aalborg University

Publications and helpful links

General Publications

• Petersen KK, Andersen HH, Tsukamoto M, Tracy L, Koenig J, Arendt-Nielsen L. The effects of propranolol on heart rate variability and quantitative, mechanistic, pain profiling: a randomized placebo-controlled crossover study. Scand J Pain. 2018 Jul 26;18(3):479-489. doi: 10.1515/sjpain-2018-0054.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: June 17, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: N-20150055