Background & Aims

Heart rate variability (HRV) is a common measure of autonomic cardiovascular activity. Higher HRV parameters reflect greater vagal (parasympathetic) activity. The parasympathetic system, along with the sympathetic system, responds to various stressors, including pain, and tries to restore cardiovascular balance. Vagal nerve activation may also reduce clinical pain and experimental pain sensitivity through descending endogenous analgesia.

Previous research in autistic people investigated the HRV responses to social and general stress, indicating lower HRV and impaired vagal reactivity. However, these HRV changes have not been studied in relation to the increased pain sensitivity reported in high-functioning autistic people (Hoffman et al., 2023).

In this study, we explored the association between experimental pain sensitivity and HRV in high-functioning autistic adults.

Methods

We assessed experimental pain sensitivity in 74 autistic adults and 88 neurotypical healthy controls (age and sex-matched) in response to 20 phasic noxious heat stimuli (PATHWAY, Medoc, Israel), forearm, delivered at a temperature eliciting pain intensity of 50 on a 0-100 NPS. Mean pain intensity ratings during phasic pain stimuli, and a minute following stimuli termination (i.e. aftersensation) were calculated.
HRV (Empatica E4 wristband, USA) was measured during 3 phases: baseline, phasic pain stimuli (i.e. reactive phase), and aftersensation. Two established parameters of vagal activity were calculated: the root mean square of the successive differences (RMSSD) and the proportion of NN50 divided by the total number of NN (R-R) intervals (pNN50).
The rmANOVA explored the effect of group, phase, and their interaction, on the HRV parameters. Within each group, we tested the associations between baseline vagal activity and pain ratings of the phasic pain stimuli and aftersensation.

Results

A group effect was found, indicating lower vagal activity in autistic people compared to neurotypical controls (RMSSD, p=0.012; pNN50, p=0.024). A phase effect was also found (RMSSD, p<0.001; pNN50, p=0.004). Interestingly, both groups had similar patterns of increased vagal response during pain and aftersensation compared to baseline. No influence of the stimulation temperature was indicated. Additionally, vagal activity and pain ratings were differently related across groups. In the autistic group, higher baseline vagal activity correlated with lower experimental pain (Spearman ?=-0.316, p=0.044 for RMSSD; ?=-0.303, p=0.054 for pNN50) and aftersensation (Spearman ?=-0.344, p=0.028 for RMSSD; ?=-0.335, p=0.032 for pNN50) pain ratings, while no significant correlations were found in the control group for any of these parameters.

Conclusions

This study elicited two main findings: (1) The autistic group had lower vagal activity but, contrary to our expectation, showed no change in their reactivity pattern, compared to the control group, indicating effective activation of the cardiovascular parasympathetic system in response to pain. (2) The correlations between higher baseline vagal activity and lower pain sensitivity in people with autism highlight the protective role of the vagus via inducing endogenous analgesia in pain hyper-sensitive populations (i.e. our autistic cohort).

References

Hoffman T, Bar-Shalita T, Granovsky Y, Gal E, Kalingel-Levi M, Dori Y, Buxbaum C, Yarovinsky N, Weissman-Fogel I. Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism. Pain. 2023 Apr 1;164(4):791-803.

Presenting Author

Yelena Granovsky

Poster Authors

Yelena Granovsky

PhD

Rambam Health Care Campus

Lead Author

Merry Kalingel-Levi

Lead Author

Tseela Hoffman

Lead Author

Einat Gal

Lead Author

Irit Weissman-Fogel

University of Haifa

Lead Author

Tami Bar-Shalita

Tel-Aviv University

Lead Author

Topics

  • Pain in Special Populations: Intellectual, Developmental, and Functional Disability