The Relationship Between Heart Rate Variability, Psychological Flexibility, and Pain in Neurofibromatosis Type 1

Individuals with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) can experience chronic pain. Previous research has examined the relationship between heart rate variability (HRV) and persistent pain. HRV is an index of autonomic nervous system functioning, and reflects the variability in time elapsed between heartbeats. Patients with chronic pain tend to exhibit lower HRV, which has been associated with poor adaptability, or psychological flexibility, to stress. The aim of the current study was to examine relationships between HRV, psychological flexibility, and pain in a sample of adolescents and young adults (AYAs) with NF1 and PNs. AYA participants (n = 40) 16 to 34 years of age with NF1 completed baseline measures of pain and psychological functioning, and underwent a 5‐minute electrocardiogram (ECG). A subset of 20 participants completed follow‐up questionnaires and a second ECG 8 weeks later. Spectral analyses of ECGs yielded a measure of high‐frequency heart rate variability (HF‐HRV). Baseline correlations revealed that lower HF‐HRV is related to greater inflexibility and more pain interference, but not pain intensity. Moreover, psychological inflexibility significantly mediated the relationship between HF‐HRV and pain interference. Finally, regression models indicated that baseline psychological inflexibility is a significant predictor of HF‐HRV at follow‐up and, separately, that baseline HF‐HRV significantly predicted pain intensity at follow‐up. These findings suggest complex mind–body processes in the experience of pain in NF1, which have not been studied previously. Implications for pain‐related interventions and future research are discussed.

[1]  Kristopher J Preacher,et al.  Mediation Analysis in Social Psychology: Current Practices and New Recommendations , 2011 .

[2]  F. Aarsen,et al.  Health-related quality of life in children with neurofibromatosis type 1: contribution of demographic factors, disease-related factors, and behavior. , 2009, The Journal of pediatrics.

[3]  P. Jacobsen,et al.  Measurement of depressive symptoms in cancer patients: evaluation of the Center for Epidemiological Studies Depression Scale (CES-D). , 1999, Journal of psychosomatic research.

[4]  S. Hayes,et al.  Psychological flexibility as a mediator of improvement in Acceptance and Commitment Therapy for patients with chronic pain following whiplash , 2010, European journal of pain.

[5]  L. McCracken,et al.  A Comprehensive Examination of Changes in Psychological Flexibility Following Acceptance and Commitment Therapy for Chronic Pain , 2016, Journal of Contemporary Psychotherapy.

[6]  B. Widemann,et al.  Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social‐emotional functioning, and quality of life , 2015, American journal of medical genetics. Part A.

[7]  L. von Essen,et al.  Acceptance as a Mediator for Change in Acceptance and Commitment Therapy for Persons with Chronic Pain? , 2015, International Journal of Behavioral Medicine.

[8]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[9]  H. Moll,et al.  Parental reports of health-related quality of life in young children with neurofibromatosis type 1: influence of condition specific determinants. , 2007, The Journal of pediatrics.

[10]  L. McCracken,et al.  A short version of the Pain Anxiety Symptoms Scale (PASS-20): preliminary development and validity. , 2002, Pain research & management.

[11]  D. Amtmann,et al.  Development of a PROMIS item bank to measure pain interference , 2010, PAIN.

[12]  J. Thayer,et al.  Heart Rate Variability, Prefrontal Neural Function, and Cognitive Performance: The Neurovisceral Integration Perspective on Self-regulation, Adaptation, and Health , 2009, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[13]  Allison C White,et al.  Are we Speaking the Same Language? , 1993 .

[14]  J. Thayer,et al.  eview meta-analysis of heart rate variability and neuroimaging studies : Implications or heart rate variability as a marker of stress and health , 2012 .

[15]  D. Turk,et al.  Biopsychosocial perspective on chronic pain. , 1996 .

[16]  Richard Gevirtz,et al.  Heart Rate Variability as a Marker of Self-Regulation , 2011, Applied psychophysiology and biofeedback.

[17]  John G. Lynch,et al.  Reconsidering Baron and Kenny: Myths and Truths about Mediation Analysis , 2010 .

[18]  D. Turk,et al.  Detecting depression in chronic pain patients: adequacy of self-reports. , 1994, Behaviour research and therapy.

[19]  S. Huson,et al.  Von Recklinghausen neurofibromatosis: a clinical and population study in south-east Wales , 1988 .

[20]  J. Tonsgard,et al.  Patient-reported outcomes in neurofibromatosis and schwannomatosis clinical trials , 2013, Neurology.

[21]  Paula G. Williams Self-regulation, executive functioning, and neurovisceral integration , 2010, PAIN.

[22]  Julian F Thayer,et al.  Lower Resting State Heart Rate Variability Relates to High Pain Catastrophizing in Patients with Chronic Whiplash‐Associated Disorders and Healthy Controls , 2016, Pain practice : the official journal of World Institute of Pain.

[23]  R. Lane,et al.  A model of neurovisceral integration in emotion regulation and dysregulation. , 2000, Journal of affective disorders.

[24]  C. Woolf Central sensitization: Implications for the diagnosis and treatment of pain , 2011, PAIN.

[25]  B. Appelhans,et al.  Heart Rate Variability as an Index of Regulated Emotional Responding , 2006 .

[26]  Kimberly J. Johnson,et al.  Neurofibromatosis type 1 , 2017, Nature Reviews Disease Primers.

[27]  Brooke E. Magnus,et al.  Psychometric properties of the PROMIS® pediatric scales: precision, stability, and comparison of different scoring and administration options , 2014, Quality of Life Research.

[28]  B. Appelhans,et al.  Heart rate variability and pain: Associations of two interrelated homeostatic processes , 2008, Biological Psychology.

[29]  S. Steinberg,et al.  NF1 plexiform neurofibroma growth rate by volumetric MRI , 2007, Neurology.

[30]  B. Widemann,et al.  Acceptance and commitment therapy in youth with neurofibromatosis type 1 (NF1) and chronic pain and their parents: A pilot study of feasibility and preliminary efficacy , 2016, American journal of medical genetics. Part A.

[31]  M. Jensen,et al.  Clinical Trial Methodology of Pain Treatment Studies: Selection and Measurement of Self-Report Primary Outcomes for Efficacy , 2011, Regional Anesthesia & Pain Medicine.

[32]  A. Dachman,et al.  CT imaging in adults with neurofibromatosis‐1 , 1998, Neurology.

[33]  T. Kashdan,et al.  Psychological flexibility as a fundamental aspect of health. , 2010, Clinical psychology review.

[34]  R. Friedrich,et al.  Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas , 2008, Journal of Medical Genetics.

[35]  G. Crombez,et al.  Psychometric Evaluation of the Pain Anxiety Symptoms Scale (PASS) in Chronic Pain Patients , 2004, Journal of Behavioral Medicine.

[36]  S. Segerstrom,et al.  Executive Functions, Self-Regulation, and Chronic Pain: A Review , 2009, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[37]  D. Borsook,et al.  Psychological processing in chronic pain: A neural systems approach , 2014, Neuroscience & Biobehavioral Reviews.

[38]  L. McCracken,et al.  Comparing the role of psychological flexibility and traditional pain management coping strategies in chronic pain treatment outcomes. , 2010, Behaviour research and therapy.

[39]  M. Lekander,et al.  The Psychological Inflexibility in Pain Scale (PIPS) – Statistical properties and model fit of an instrument to assess change processes in pain related disability , 2010, European journal of pain.

[40]  L. McCracken,et al.  Are We Speaking the Same Language? Finding Theoretical Coherence and Precision in "Mindfulness-Based Mechanisms" in Chronic Pain. , 2017, Pain medicine.

[41]  A. Vincent,et al.  Self‐Regulatory Fatigue: A Missing Link in Understanding Fibromyalgia and Other Chronic MultiSymptom Illnesses , 2017, Pain practice : the official journal of World Institute of Pain.

[42]  M. Ingvar,et al.  Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgeia , 2012, PAIN.

[43]  A. Hayes PROCESS : A Versatile Computational Tool for Observed Variable Mediation , Moderation , and Conditional Process Modeling 1 , 2012 .

[44]  J. Tonsgard Clinical manifestations and management of neurofibromatosis type 1. , 2006, Seminars in pediatric neurology.

[45]  A. Hayes Beyond Baron and Kenny: Statistical Mediation Analysis in the New Millennium , 2009 .

[46]  S. Khalsa,et al.  The hierarchical basis of neurovisceral integration , 2017, Neuroscience & Biobehavioral Reviews.

[47]  S. Segerstrom,et al.  Self-regulatory deficits in fibromyalgia and temporomandibular disorders , 2010, PAIN.

[48]  B. Ditto,et al.  Short-term autonomic and cardiovascular effects of mindfulness body scan meditation , 2006, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[49]  Niloofar Afari,et al.  Health and distress predictors of heart rate variability in fibromyalgia and other forms of chronic pain. , 2012, Journal of psychosomatic research.

[50]  H. Trompetter,et al.  Acceptance- and mindfulness-based interventions for the treatment of chronic pain: a meta-analytic review , 2016, Cognitive behaviour therapy.

[51]  André Diedrich,et al.  Interacting influences of gender and chronic pain status on parasympathetically mediated heart rate variability in adolescents and young adults , 2017, Pain.

[52]  Mara Mather,et al.  Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults , 2016, NeuroImage.

[53]  J. Vlaeyen,et al.  Beyond nociception: the imprecision hypothesis of chronic pain. , 2015, Pain.

[54]  K. Jackson,et al.  The CES-D as a screen for depression and other psychiatric disorders in adolescents. , 1991, Journal of the American Academy of Child and Adolescent Psychiatry.