Heart Rate Variability Measures Are Not a Surrogate Marker for Pain Intensity

Heart rate variability was not determined to be suitable as a biomarker for pain intensity among patients with chronic pain.

Authors of a study published in Pain found that individual heart rate variability (HRV) parameters are not suitable surrogates for pain intensity in the setting of chronic pain.

Patients (N=363) with chronic pain were recruited from the Universitair Ziekenhuis Brussels and the Pain Clinic of AZ Delta in Belgium to participate in this observational, cross-sectional study (ClinicalTrials.gov Identifier: NCT04539353). Participants were offered a consultation during which they responded to questionnaires about pain outcomes and underwent a 5-minute HRV recording session. The relationship between pain intensity and HRV parameters was evaluated using a canonical correlation analysis.

The mean age of study patients was 56.3 (standard deviation [SD], 14.01) years, 67.22% were women, most (n=257) had musculoskeletal pain, median Medication Quantification Scale (MQS) score was 5.6 (interquartile range [IQR], 1.9-10.7) points, the average numeric rating scale (NRS) score for pain was 7 (IQR, 5-8) points, and the average visual analogue scale (VAS) score for pain was 60.3 (SD, 21.48) mm.

In the univariate analysis, no significant correlations were established between the 16 HRV measures and the 4 pain intensity scores. Among HRV measures, strong negative correlations were identified among heart rate, interbeat interval, normalized low frequency, and normalized high frequency parameters. The 4 pain scores were positively correlated.

Despite the biological knowledge underpinning the association between HRV and pain intensity, individual-level surrogacy could not be demonstrated in this population.

In the canonical correlation analysis, the null hypothesis that all correlations were 0 was rejected for both NRS (Λ, 0.814; P <.001) and VAS (Λ, 0.803; P <.001) pain outcomes. In the NRS and VAS analyses, the first canonical correlations accounted for 14.2% and 14.97% and the HRV, and clinical parameter redundancies accounted for 11% and 12.4% of the variance in pain scores, respectively.

The highest individual HRV measure correlations were associated with mean heart rate,  which estimated mean NRS with no medication use (R2, 0.0961) and with medication use (R2, 0.0209).

The average and current NRS and VAS pain scores were stratified into mild (NRS, 1-3 points; VAS, >31 mm), moderate (NRS, 4-6 points; VAS, 31-54 mm), and severe (NRS, 7-10 points; VAS, 55-100 mm) categories. In general, most patients fell into the severe pain group for the 4 measures (range, 45.2%-63.6%).

When pain was used as a categorical variable in the model, mean heart rate remained the best predictor (R2, 0.022).

This study may have been limited by including patients with different types of chronic pain.

Study authors conclude, “Despite the biological knowledge underpinning the association between HRV and pain intensity, individual-level surrogacy could not be demonstrated in this population. This indicates that HRV is not a biomarker that could substitute a pain intensity reporting in clinical practice.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Moens M, Billet B, Molenberghs G, et al. Heart rate variability is not suitable as surrogate marker for pain intensity in patients with chronic pain. Pain. Published online January 19, 2023. doi:10.1097/j.pain.0000000000002868