Patients with Rett syndrome may manifest altered pain perception/experience and are vulnerable to conditions associated with chronic pain. Pain response is difficult to measure, however, because of severe communicative impairment. There is also documented autonomic dysfunction, including decreased heart rate variability. Given the relation between pain and the autonomic nervous system, we tested the feasibility of using resting heart rate variability to predict nonverbal pain/discomfort behavior during a standardized modified quantitative sensory test in Rett syndrome. All stimulus applications resulted in increased behavioral reactivity compared to baseline, with repeated von Frey significantly greater than all other stimuli. Resting heart rate variability predicted behavioral reactivity to repeated von Frey. These preliminary findings provide feasibility evidence for an integrated autonomic-sensory measurement approach and are consistent at a construct level with preclinical evidence in Rett syndrome. Further work is needed to determine how heart rate variability changes during stimulus application.
Bibliographical noteFunding Information:
We would like to thank all the participants and their families, as well as RettSyndrome.org , without whom this work would not be possible. Thanks also to Ashley Nelson, Christopher Lindgren, Mia Koski, and Michael Gleaves for their technical assistance coding the behavioral data for this project. We would also like to thank the National Institute of Child Health and Human Development, RettSyndrome.org (formerly the International Rett Syndrome Foundation), and the Mayday Fund for their support. Author Contributions AMM and BJB are co–first authors who contributed equally to the work. AMM, BJB, ACD, and JH collected the data; AMM, CCB, BJB, and FJS contributed to the creation of the behavioral coding system; BJB and AMM analyzed the cardiac data and behavioral reactivity analyses, respectively; BB performed the statistical modeling; and AB, TJF, and AAB contributed to interpretation of the results. AMM, BJB, and FJS drafted significant portions of the manuscript. All authors critically reviewed the manuscript. Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BJB, JH, ACD, CCB, and FJS declare funding from the National Institute of Child Health and Human Development. AMM, BJB, and ACD declare funding from Rettsyndrome.org (formerly International Rett Syndrome Foundation). CCB and FJS declare funding from the Mayday Fund. The other authors declare no conflicts of interest related to this study. Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported, in part, by the National Institute of Child Health and Human Development grant No. 44763, RettSyndrome.org (formerly the International Rett Syndrome Foundation), and the Mayday Fund. No funder had involvement in the study design, collection, analysis, interpretation of the data, or preparation or submission of this manuscript. ORCID iD Alyssa M. Merbler, MA https://orcid.org/0000-0002-8038-3368 Ethical Approval This study was approved by the University of Minnesota Human Research Protection Program’s Institutional Review Board prior to data collection (IRB no.: 1105M99437). All participants’ parents/legal guardians provided informed, written consent prior to data collection.
© The Author(s) 2019.
- Rett syndrome
- heart rate variability
- quantitative sensory testing