Heart Rate Variability and Autonomic Function: A Study of Adolescents with Chronic Abdominal Pain and Healthy Adolescents

Background: Chronic abdominal pain is often accompanied by autonomic dysfunction. It is hypothesized that dysregulation of the autonomic nervous system (ANS) results in poorer physiological modulation to physical and psychological stress in the context of persistent pain. Research in adults with chronic pain conditions identified decreased parasympathetic activation using heart rate variability (HRV), as a measure of ANS function. However, data are limited in pediatric chronic abdominal pain populations. Thus, the objectives were to: 1) characterize and compare the subjective and objective (HRV) assessment of autonomic dysfunction in adolescents with chronic abdominal pain to pain-free adolescents, 2) investigate the association of psychological factors (anxiety, depression and pain catastrophizing) with the subjective and objective autonomic dysfunction in adolescents with chronic abdominal pain, and 3) quantify and compare HRV under a psychologically stressful condition between adolescents with chronic abdominal pain and pain-free adolescents.Methods: This was a prospective study of adolescents with chronic abdominal pain and pain-free adolescents. Adolescents with chronic abdominal pain were recruited from Seattle Children’s Hospital’s (SCH) Gastroenterology and Pain Medicine Clinics; pain-free adolescents were recruited through mailings from Seattle Children’s Hospital (October 2019 to April 2022). Adolescents completed questionnaire measures on abdominal pain severity, pain-related disability, autonomic dysfunction, anxiety, depression, and pain catastrophizing. Adolescents also underwent continuous monitoring of HRV in the laboratory whilst undergoing the Trier Social Stress Test which included a baseline relaxed state, and an experimentally induced psychological stress state. The HRV parameters tested were the time-domain index root mean square of the successive differences of NN intervals (RMSSD) and frequency-domain index of the proportion of HRV occurring at low frequency (LF). Results: There were 60 adolescents, 33 with chronic abdominal pain, and 27 pain-free peers (females = 68.3%, mean age = 16.3 years, SD = 0.2) enrolled in the study. The groups were similar with respect to age, race, and ethnicity, with proportionately more females in the group with chronic abdominal pain. Adolescents in the chronic abdominal pain group reported an average pain intensity of 5.0 (SD = 2.2) on the 0 to 10 Numerical Rating Scale, and had clinically high levels of anxiety, depression, and pain catastrophizing. Multivariable analysis revealed that adolescents with chronic pain had, on average, a 22.3-point higher COMPASS31 scores compared to pain-free adolescents (p < 0.001, 95% confidence interval (CI): 14.1, 30.5) after adjusting for age and sex. For objective measures of HRV, adolescents with chronic pain had lower RMSSD by 157 msec2 (95% CI: -331, 17.5), and lower LF by 337 (95% CI: -1023, 350), however these differences were not statistically significant (RMSSD: p = 0.07, LF: p = 0.33) when adjusting for age and sex. Specific to adolescents with chronic abdominal pain, tests of the associations between anxiety, depression, and pain catastrophizing with self-reported autonomic dysfunction or HRV parameters (RMSSD, LF) were not statistically significant after accounting for age, sex, and abdominal pain severity. In a linear mixed model for RMSSD, the impact of induced stress (compared to baseline) for adolescents with chronic abdominal pain was not significantly different than what was seen in pain-free adolescents (130.9 msec2 higher, 95% CI: -159, 240), p = 0.37). LF was 1243.73 higher (95% CI: 374, 2113) for adolescents with chronic abdominal pain due to the impact of induced stress (from baseline assessment; p = 0.006) compared to pain-free adolescents. Conclusion: Adolescents with chronic abdominal pain evidenced greater autonomic symptomatology on subjective report compared to pain-free adolescents, however HRV parameters (RMSSD, LF) were not significantly different between groups. For adolescents with chronic abdominal pain, there was no statistically significant association between self-reported autonomic dysfunction or HRV parameters with the tested psychological factors. Compared to pain-free peers, adolescents with chronic abdominal pain had significantly higher increases in LF but not RMSSD from baseline to induced stress compared to pain-free peers. Findings in this study need to be replicated given the small sample sizes, and the differences identified with regard to time- versus frequency-domain HRV parameters.