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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

CiteScore 2018: 0.85

SCImago Journal Rank (SJR) 2018: 0.494
Source Normalized Impact per Paper (SNIP) 2018: 0.427

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Volume 18, Issue 3


The effects of propranolol on heart rate variability and quantitative, mechanistic, pain profiling: a randomized placebo-controlled crossover study

Kristian Kjær Petersen
  • Corresponding author
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Aalborg, Denmark
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hjalte Holm Andersen
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Masato Tsukamoto
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Clinical Development Department, Asahi Kasei Pharma Corporation, Tokyo, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lincoln Tracy
  • School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, VIC, Australia
  • School of Psychology, Faculty of Health Sciences, Australian Catholic University, VIC, Australia
  • Pain Management and Research Centre, Caulfield Hospital, VIC, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Julian Koenig
  • Section for Translational Psychobiology in Child and Adolescent Psychiatry, Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany
  • University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lars Arendt-Nielsen
  • SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-06-02 | DOI: https://doi.org/10.1515/sjpain-2018-0054


Background and aims

The autonomic nervous system (ANS) is capable of modulating pain. Aberrations in heart rate variability (HRV), reflective of ANS activity, are associated with experimental pain sensitivity, chronic pain, and more recently, pain modulatory mechanisms but the underlying mechanisms are still unclear. HRV is lowered during experimental pain as well as in chronic pain conditions and HRV can be increased by propranolol, which is a non-selective β-blocker. Sensitization of central pain pathways have been observed in several chronic pain conditions and human mechanistic pain biomarkers for these central pain pathways include temporal summation of pain (TSP) and conditioned pain modulation (CPM). The current study aimed to investigate the effect of the β-blocker propranolol, and subsequently assessing the response to standardized, quantitative, mechanistic pain biomarkers.


In this placebo-controlled, double-blinded, randomized crossover study, 25 healthy male volunteers (mean age 25.6 years) were randomized to receive 40 mg propranolol and 40 mg placebo. Heart rate, blood pressure, and HRV were assessed before and during experimental pain tests. Cuff pressure pain stimulation was used for assessment of pain detection (cPDTs) and pain tolerance (cPTTs) thresholds, TSP, and CPM. Offset analgesia (OA) was assessed using heat stimulation.


Propranolol significantly reduced heart rate (p<0.001), blood pressure (p<0.02) and increased HRV (p<0.01) compared with placebo. No significant differences were found comparing cPDT (p>0.70), cPTT (p>0.93), TSP (p>0.70), OA-effect (p>0.87) or CPM (p>0.65) between propranolol and placebo.


The current study demonstrated that propranolol increased HRV, but did not affect pressure pain sensitivity or any pain facilitatory or modulatory outcomes.


Analgesic effects of propranolol have been reported in clinical pain populations and the results from the current study could indicate that increased HRV from propranolol is not associated with peripheral and central pain pathways in healthy male subjects.

Keywords: β-blockers; heart rate variability; conditioned pain modulation; offset analgesia; temporal summation of pain; pressure pain threshold


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About the article

Corresponding author: Kristian Kjær Petersen, Associate Professor, PhD, SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7 D3, DK-9220 Aalborg, Denmark, Phone: +45 9940 7529, Fax: +45 9815 4008

Received: 2018-03-12

Revised: 2018-04-13

Accepted: 2018-04-23

Published Online: 2018-06-02

Published in Print: 2018-07-26

Authors’ statements

Research funding: The authors thank The Innovation Fund Denmark (j.no. 136-2014-5), The Shionogi Science Program and the TaNeDS Europe grant for providing the opportunity to conduct the study.

Conflict of interest: Masato Tsukamoto is an employee of Asahi Kasei Pharma Corporation.

Informed consent: All participants were given oral and written information and signed written informed consent prior to the initiation of the study.

Ethical approval: The study complied with the Helsinki Declaration, was approved by the local Ethical Committee (reference number: N-20120043), and registered at ClinicalTrials.gov (registration number: NCT02808611).

Citation Information: Scandinavian Journal of Pain, Volume 18, Issue 3, Pages 479–489, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-0054.

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