Heart rate variability is not suitable as a surrogate marker for pain intensity in patients with chronic pain

The search towards more objective outcome measurements and consequently surrogate markers for pain started decades ago; however, no generally accepted biomarker for pain has qualified yet. The goal is to explore the value of heart rate variability (HRV) as surrogate marker for pain intensity chronic pain setting. Pain intensity scores and HRV were collected in 366 patients with chronic pain, through a cross-sectional multicenter study. Pain intensity was measured with both the visual analogue scale and numeric rating scale, whereas 16 statistical HRV parameters were derived. Canonical correlation analysis was performed to evaluate the correlation between the dependent pain variables and the HRV parameters. Surrogacy was determined for each HRV parameter with point estimates between 0 and 1 whereby values close to 1 indicate a strong association between the surrogate and the true endpoint at the patient level. Weak correlations were revealed between HRV parameters and pain intensity scores. The highest surrogacy point estimate was found for mean heart rate as marker for average pain intensity on the numeric rating scale with point estimates of 0.0961 (95% confidence interval [CI] 0.0384-0.1537) and 0.0209 (95% CI 0-0.05) for patients without medication use and with medication, respectively. This study indicated that HRV parameters as separate entities are no suitable surrogacy candidates for pain intensity, in a population of chronic pain patients. Further potential surrogate candidates and clinical robust true endpoints should be explored, to find a surrogate measure for the highly individual pain experience.

Automated summary

The search for a biomarker for pain has been ongoing for decades, but no widely accepted biomarker has been identified. This study explored the use of heart rate variability (HRV) as a surrogate marker for pain intensity in chronic pain patients. The study found weak correlations between HRV parameters and pain intensity scores, suggesting that HRV parameters are not suitable as surrogate candidates for pain intensity. Further research is needed to identify potential surrogate markers and true endpoints for the highly individual pain experience.