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

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 beta-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 beta-blocker propranolol, and subsequently assessing the response to standardized, quantitative, mechanistic pain biomarkers. Methods: 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. Results: 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. Conclusions: The current study demonstrated that propranolol increased HRV, but did not affect pressure pain sensitivity or any pain facilitatory or modulatory outcomes. Implications: 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.