Heart rate variability (HRV) in juvenile fibromyalgia: a preliminary study

Abstract

Background

Juvenile fibromyalgia (JFM) is a chronic pain condition affecting children and adolescents, often accompanied by emotional distress. Evidence suggests that autonomic dysregulation, as measured by reduced heart rate variability (HRV), may play a key role in symptom expression. This study aimed to explore clinical, emotional, and physiological differences between children with and without JFM.

Methods

This observational cross-sectional study enrolled 30 participants aged 8 to 17, divided into two equal groups based on JFM diagnosis according to ACR 2010 criteria. Clinical evaluation included Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Numerical Rating Scale (NRS), and the Multidimensional Anxiety Scale for Children – Second Edition (MASC-2). HRV coherence was measured using the emWave Pro system. Group comparisons were analyzed using non-parametric Wilcoxon tests. Correlations were assessed with Spearman’s rank-order test, and logistic regression was used to examine HRV as a predictor of JFM.

Results

Children with JFM showed significantly higher levels of pain and anxiety compared to controls (p < 0.001), and significantly lower HRV coherence (mean 0.91 vs. 1.27; p < 0.01). Inverse correlations were found between HRV and symptom severity (WPI, SSS) as well as anxiety levels.

Conclusions

Reduced HRV coherence is associated with greater symptom burden and psychological distress in children with JFM. These preliminary findings suggest that HRV may represent a potential biomarker in pediatric fibromyalgia, but larger and more robust studies are required before drawing firm conclusions. HRV biofeedback may offer a supportive, non-pharmacological approach for improving autonomic regulation and managing chronic pain in youth.

Trial registration

Not applicable. This observational study was not registered as it did not involve a healthcare intervention.

Introduction

Musculoskeletal pain is common in children and adolescents and frequently results in medical consultation [1]. When pain persists for at least three months, it is defined as chronic and is often associated with a significant impact on daily functioning and psychological well-being [2].

Chronic musculoskeletal pain is generally classified into two main categories: disease-related pain and primary chronic pain conditions. Disease-related pain is associated with identifiable organic pathology, such as juvenile dermatomyositis (muscle involvement) or juvenile idiopathic arthritis (joint involvement). Primary chronic pain conditions, instead, include syndromes such as juvenile fibromyalgia (JFM), complex regional pain syndrome (CRPS), and idiopathic back pain, where pain occurs without clear underlying tissue pathology [2, 3].

Primary chronic musculoskeletal pain conditions are classified based on the distribution of pain [2–4], which may be widespread—as in JFM—or localized, as in CRPS or idiopathic back pain [3]. An increasing body of evidence indicates that enhanced pain signal processing and/or reduced inhibitory control within the nervous system significantly contribute to the pathophysiology of these conditions, which are now categorized as central sensitisation pain syndromes [5].

It is estimated that JFM affects between 2.1% and 6.1% of school-aged children, with a predominance among adolescent girls [6]. The prevalence of fibromyalgia is markedly higher among individuals with chronic illnesses.

Studies on adults estimate that rates may rise to approximately 30% in patients with rheumatologic conditions [7]. Individuals affected by JFM frequently report intense pain and notable functional limitations, significantly impacting daily activities and quality of life. In addition to pain, the clinical presentation often includes a constellation of somatic and neurovegetative symptoms, such as profound fatigue, non-restorative sleep, chronic headaches, and irritable bowel syndrome (IBS) [3]. Yunus and Masi first defined criteria for JFM in 1985, emphasizing chronic widespread pain with fatigue, sleep issues, anxiety, and tender points. Later studies showed that ACR criteria also apply to juveniles [6].

Heart rate variability (HRV) is the variation in time intervals between consecutive heartbeats and reflects autonomic nervous system activity. In individuals with normal HRV, there is a dynamic balance between parasympathetic and sympathetic branches, enabling adaptive responses to cognitive and environmental stressors. Thus, HRV is a marker of the body’s physiological flexibility and resilience [8]. Research has shown that individuals with anxiety, depression, or other psychopathological conditions often exhibit impaired autonomic regulation, characterized by sympathetic overactivity and reduced HRV [9]This pattern has also been observed in pediatric populations [10] Similarly, patients with fibromyalgia display reduced HRV. Studies suggest a proportional relationship between HRV reduction and increased pain perception [11].

Therapeutic approaches for managing juvenile fibromyalgia, as proposed in the scientific literature, include a combination of physical activity, cognitive-behavioral therapy (CBT), and biofeedback techniques. Among these, heart rate variability biofeedback (HRVB) has shown particular promise in adult fibromyalgia and in other pediatric chronic pain conditions. However, it has not yet been specifically tested in JFM. HRVB may enhance autonomic regulation by improving HRV, thereby promoting greater stress resilience, emotional adaptability, and a reduction in perceived pain [12]. Supporting this, a recent pilot study demonstrated that a brief HRV biofeedback intervention, when combined with guided breathing exercises practiced at home, was associated with amelioration of chronic pain symptoms, suggesting its potential as a low-risk, non-pharmacological adjunct in the management of chronic pain conditions such as JFM [13].

Emerging evidence suggests that JFM frequently persists into adulthood, often accompanied by chronic physical and psychological symptoms, thereby underscoring the importance of early diagnosis and timely intervention. However, compared to the extensive body of research on fibromyalgia in adults, knowledge regarding its pathophysiology, clinical course, and optimal treatment strategies in the pediatric population remains limited. Furthermore, considering the scarcity of empirical data and the potential utility of HRV as a physiological marker in children and adolescents, this aimed to evaluate clinical and HRV parameters in a cohort of patients diagnosed with JFM, followed at the Pediatric Rheumatology and Immunology Unit in Lecce, Italy, thereby contributing to this underexplored area of research [12, 14].

Material and methods

Aim, design, and setting of the study

This study aimed to assess the clinical, psychological, and physiological features of children and adolescents diagnosed with juvenile fibromyalgia (JFM) compared to healthy controls. It was conducted as a cross-sectional, observational study at the Pediatric Rheumatology and Immunology Unit of the Vito Fazzi Hospital in Lecce, Italy, as part of a single-center, non-pharmacological research program.

Participants and eligibility criteria

Thirty participants aged 8 to 17 years were enrolled, divided into two groups: 15 children with JFM and 15 healthy controls matched for age and sex. Healthy controls were recruited from the general pediatric outpatient clinic of our hospital, and only children without chronic or acute illnesses at the time of assessment were included. Inclusion criteria for the JFM group were: a diagnosis of juvenile fibromyalgia based on the 2010 American College of Rheumatology (ACR) criteria [6, 15], and a minimum symptom duration of three months. The diagnostic thresholds were WPI ≥ 7 and SSS ≥ 5, or WPI between 3 and 6 and SSS ≥ 9. Although updated criteria were published in 2016, the 2010 criteria were adopted given their better suitability for pediatric populations [15].

Exclusion criteria included use of medications affecting autonomic function or pain perception (such as antidepressants, benzodiazepines, NSAIDs, beta-blockers) within two weeks before enrollment, other chronic illnesses, or inability to comply with study procedures.

Informed consent was obtained from parents or legal guardians. The study was approved by the Ethics Committee of the “Giovanni Paolo II” Cancer Institute of Bari (Protocol code no. 656, approved on September 12, 2024).

Procedures and measures

Participants in the JFM group underwent a baseline heart rate variability (HRV) coherence assessment, followed by a single HRV biofeedback session with a licensed psychologist, using the emWave Pro system (HeartMath, Boulder Creek, CA), a validated non-invasive tool for autonomic regulation analysis. Only the assessment data collected prior to the biofeedback session were included in the present analyses [16]. HRV was recorded at rest over a 5-minute session using a plethysmographic sensor applied to the earlobe or finger.

Clinical assessments included:

• Widespread Pain Index (WPI) – evaluates pain across 19 anatomical regions

• Symptom Severity Scale (SSS) – includes fatigue, cognitive symptoms, and somatic burden

• Numerical Rating Scale (NRS) – self-reported pain severity from 0 to 10

• Multidimensional Anxiety Scale for Children – Second Edition (MASC-2) – measures anxiety in youth aged 8–19 years

The control group completed only baseline HRV and MASC-2 assessments.

Statistical analysis

The study sample was stratified according to JFM status to assess differences in clinical, demographic, and physiological variables. To determine the appropriate statistical approach, the distribution of continuous variables was evaluated using the Shapiro–Wilk test for normality, while Bartlett’s test was employed to assess the assumption of homogeneity of variances across groups. Due to the presence of non-normal distributions and the relatively small size of some subgroups, a non-parametric statistical approach was adopted.

Comparisons between participants with and without JFM were conducted using the Wilcoxon rank-sum test (also known as the Mann–Whitney U test) for continuous variables. This method was selected due to its robustness to violations of normality and heteroscedasticity. A two-sided p-value < 0.05 was considered statistically significant for all analyses.

To explore potential associations among continuous and ordinal variables, such as HRV indices, symptom severity, psychological scores, and age, a Spearman’s rank-order correlation matrix was constructed. This non-parametric measure was chosen for its ability to detect monotonic relationships regardless of linearity or normality. Where appropriate, Bonferroni correction was applied to adjust for multiple comparisons.

A box plot was generated to visualize the distribution of HRV metrics according to JFM status. This visualization facilitated comparison between groups by highlighting central tendency, interquartile ranges, and potential outliers.

All statistical analyses were performed using R software (RStudio 2023.03.1 or equivalent), and visualizations were generated using the ggplot2 and corrplot packages. All tests were two-sided, and results were considered statistically significant at p < 0.05 unless otherwise specified.

Results

A total of 30 participants (mean age 12.13 ± 2.94 years; 60% female) were enrolled, with 15 diagnosed with JFM and 15 age- and sex-matched controls without JFM. Table 1 describes the demographic and clinical features of the entire cohort based on fibromyalgia status.

Table 1.

Demographic and clinical features of the entire cohort based on fibromyalgia status

	Without JF		With JF
	mean ± sd	median (iqr)	mean ± sd	median (iqr)	p
N (%)	15 (50.00)		15 (50.00)
Age (years)	12.533 ± 2.924	13 (4.5)	11.733 ± 2.963	11 (3)	0.45
Gender
0	6 (40.00)		3 (20.00)		0.42
1	9 (60.00)		12 (80.00)
Disease Onset Age (years)	--	--	8.867 ± 2.2	9 (2.5)	--
Diagnosis Delay	--	--	1.86 ± 1.409	1.1 (2.3)	--
Diagnosis Age (years)	--	--	10.8 ± 2.981	10 (3.5)	--
WPI score	--	--	9.4 ± 2.384	9 (2.5)	--
ss2a score	--	--	3.867 ± 0.743	4 (1)	--
Symptoms (n)	--	--	10.6 ± 3.397	11 (4.5)	--
ss2b score	--	--	1.6 ± 0.507	2 (1)	--
SS score	--	--	5.467 ± 0.834	5 (0.5)	--
NRS	--	--	6.467 ± 1.846	7 (2)	--
HRV	1.267 ± 0.383	1.2 (0.45)	0.907 ± 0.301	1 (0.35)	< 0.01
Family History	0 (0.00)		5 (33.30)		0.04
Chronic Disease Family History	5 (3.30)		11 (73.30)		0.02
MASC
40–54	12 (80.00)		5 (33.30)		0.02
55–59	2 (13.30)		1 (6.70)
60–64	--		2 (13.30)
65–69	--		2 (13.30)
70–90	1 (6.70)		5 (33.30)

Demographic and clinical characteristics

There were no significant differences between groups in terms of age (p = 0.45) or sex distribution (p = 0.42). Among patients with JFM, the mean age at onset was 8.87 ± 2.2 years, the mean age at diagnosis was 10.8 ± 2.98 years, and the mean diagnostic delay was 1.86 ± 1.41 years.

Each patient underwent a comprehensive assessment using the specific ACR criteria. The mean WPI score was 9.4 ± 2.38. The components of the SSS were as follows: SSS2a, 3.87 ± 0.74; symptom count, 10.6 ± 3.40; and SSS2b, 1.6 ± 0.51, resulting in an overall SSS score of 5.47 ± 0.83. Pain intensity, assessed using the NRS, had a mean value of 6.47 ± 1.85.

HRV was compared between the two groups, resulting in a significant reduction in JFM participants (mean 0.91 ± 0.30) compared to controls (mean 1.27 ± 0.38, p < 0.01), suggesting impaired autonomic regulation. This is illustrated in the box plot (Fig. 1), which shows a lower median HRV and greater dispersion in the JFM group. Figure 2 shows the Spearman’s rank correlation plot results for relationships among clinical variables.

Fig. 1.

Boxplots showing HRV distribution stratified by fibromyalgia status

Fig. 2.

Spearman’s rank correlation plot showing relationships among clinical variables

Family history and psychological features

A family history of fibromyalgia was present in 33.3% of JFM participants, compared to none in the control group (p = 0.04). Additionally, chronic disease in family members was significantly more frequent in the JFM group (73.3% vs. 33.3%, p = 0.02).

Anxiety symptom severity, assessed using the MASC-2, differed markedly between groups. A clinically significant MASC-2 score (T-score ≥ 65) was observed in 33.3% of JFM participants, versus 6.7% in controls. Furthermore, 66.7% of JFM participants scored ≥ 55, indicating elevated anxiety, compared to only 13.3% of controls (p = 0.02).

Discussion

This study examined the clinical, emotional, and physiological profiles of children and adolescents diagnosed with JFM compared to matched healthy peers, with a particular focus on autonomic regulation as measured by HRV. Our findings underscore the complex, multidimensional nature of JFM and point to significant impairments in autonomic functioning that may have diagnostic and therapeutic implications.

Patients with JFM may experience symptom onset at a particularly young age [6]. In our study, families reported the first episodes of musculoskeletal pain at a median age of 9 years. Although the median age at symptom onset reported in the literature tends to be slightly higher, the overall age range is typically broad. Diagnosing and managing the condition in younger children can be particularly challenging, while adolescents are often more accessible to clinical evaluation and intervention. In many cases, the diagnosis is made only after other conditions have been ruled out and after a relatively long period of clinical observation. This diagnostic delay often results in numerous medical consultations and tests, with the potential for significant psychological distress. In our cohort, the latency between symptom onset and diagnosis was consistent with findings from other published studies [17, 18].

Familial aggregation of fibromyalgia and other chronic pain conditions has been reported in prior studies and may reflect inherited alterations in pain processing pathways, autonomic regulation, or psychological resilience [6]. In our cohort, no cases of fibromyalgia were reported among family members of healthy controls, whereas up to one-third of patients with JFM had at least one affected relative. In addition to potential genetic factors, this correlation may also reflect behavioral influences, such as maladaptive coping responses to pain or a highly controlling family environment [19, 20].

As expected based on the inclusion criteria, WPI and SSS scores in our cohort were above the minimum thresholds required for a fibromyalgia diagnosis [15] The average values of these scores, which reflect the extent and severity of the condition, were consistent with findings reported in adult populations [21]. In the pediatric literature, data are more heterogeneous; however, cohorts with a predominance of adolescents tend to report higher scores, more closely resembling adult values [22, 23]. Studies specifically examining WPI and SSS scores exclusively in younger children remain scarce.

The dysautonomia observed in FM is marked by persistent autonomic nervous system hyperactivity at rest and diminished reactivity under stress [24, 25]. Autonomic dysfunction has been documented across a range of conditions, several of which are commonly comorbid with FM, including irritable bowel syndrome, chronic fatigue syndrome, and migraine [26].

In our study, children and adolescents with JFM exhibited a significant reduction in HRV compared to healthy controls. Although no other studies have specifically analyzed this pattern in JFM, encouraging data are available from research on chronic pain in children. Evans et al. examined 104 healthy children and 48 with various chronic pain conditions, both musculoskeletal and visceral in origin. They found that affected children had reduced resting HRV and a diminished capacity to modulate HRV in response to external stimuli [27]. In contrast, a separate study on recurrent abdominal pain reported no significant difference in HRV between cases and controls [28].

The association between reduced HRV and JFM was further supported by logistic regression analysis. HRV emerged as a significant predictor of JFM diagnosis, even after adjusting for age and sex, indicating that physiological markers of autonomic function may offer diagnostic value beyond conventional clinical evaluation. Given the small sample size, these results should be considered exploratory and interpreted with caution. In a study on adults, Ladisa et al. reported a moderate correlation between the non-linear HRV parameter D₂ and the Fibromyalgia Impact Questionnaire (FIQ), a measure of disease-specific impairment [29] To date, similar studies in pediatric populations are lacking. Considering that HRV measurement is non-invasive and well tolerated in children, it may represent not only a potential biomarker for JFM but also a useful tool to monitor progress during behavioral interventions.

Patients with JFM are well known to have an increased risk of psychopathological comorbidities, such as anxiety and depression, although the overall impact appears to be less pronounced compared to adults [6]. In our cohort, clinical measures of anxiety assessed through the MASC-2 were significantly more elevated in JFM patients compared to controls. Anxiety may amplify pain perception and autonomic arousal, creating a vicious cycle of stress and symptom exacerbation. Gmuca et al. studied 31 adolescents with JFM and found that 60% had MASC-2 scores above 60—remarkably similar to the values observed in our cohort [30].

Notably, in our cohort, HRV coherence showed a negative correlation with MASC-2 scores, indicating that children with more severe anxiety symptoms also exhibited poorer autonomic regulation. Gmuca’s group also reported, in a different analysis, a correlation between higher anxiety levels on the MASC-2 and suicidal ideation, as well as an association between suicidal ideation and greater pain intensity [31].

Taken together, these findings support the integration of psychophysiological assessment and intervention in the management of JFM. Biofeedback-based approaches, such as HRV training, may offer a promising adjunct to pharmacological treatment by targeting autonomic dysregulation and enhancing self-regulation skills [3, 13, 32]. Moreover, incorporating HRV into routine assessment could allow for more personalized and responsive treatment strategies, especially in patients with comorbid anxiety or high symptom burden.

Several limitations should be acknowledged. The relatively small sample size limits the generalizability of the findings, and the cross-sectional design precludes causal inference. Furthermore, WPI and SSS were not administered to healthy controls. Although some pain-related items would likely not have been endorsed, other symptoms included in the SSS might have been reported, and the absence of these data restricts the scope of comparisons between groups. Longitudinal studies are needed to determine whether improvements in HRV through biofeedback or other modalities translate into sustained symptom relief and functional gains. Additionally, while HRV coherence is a clinically relevant measure, it does not capture the full complexity of autonomic nervous system activity, and future studies should consider complementary physiological indices.

In light of the cross-sectional design, thus lacking a follow-up data collection, this study is proposed as seminal for future causative investigations centered on the modifications in HRV parameters after biofeedback sessions, aiming to improve autonomic balance, potentiate parasympathetic activity (rest and digestion) and reduce sympathetic activation (linked to stress) in the same young fibromyalgia population.

In conclusion, this study provides preliminary evidence that autonomic dysregulation, as measured by HRV coherence, is significantly associated with symptom severity and psychological distress in JFM. In conclusion, this preliminary study suggests an association between reduced HRV and symptom burden in JFM. While promising, these results require confirmation in larger, longitudinal cohorts before clinical applications can be defined.

Abbreviations

ACR

American College of Rheumatology

ANS

Autonomic Nervous System

CBT

Cognitive Behavioral Therapy

CI

Confidence Interval

CRPS

Complex Regional Pain Syndrome

FIQ

Fibromyalgia Impact Questionnaire

FM

Fibromyalgia

HRV

Heart Rate Variability

HRVB

Heart Rate Variability Biofeedback

IBI

Inter–Beat Interval

IBS

Irritable Bowel Syndrome

JFM

Juvenile Fibromyalgia

JIA

Juvenile Idiopathic Arthritis

MASC-2

Multidimensional Anxiety Scale for Children–Second Edition

NRS

Numerical Rating Scale

OR

Odds Ratio

SD

Standard Deviation

SSS

Symptom Severity Scale

WPI

Widespread Pain Index

Author contributions

Federico Diomeda: Conceptualization, Investigation, Data Curation, Writing - Original Draft, Writing - Review and Editing, Project administration; Brigitte Dell’Anna: Investigation, Data Curation, Writing - Review and Editing; Rossella Greco: Investigation, Data Curation, Writing - Review and Editing; Giulia Loiacono: Investigation, Data Curation, Writing - Review and Editing; Roberta Zupo: Investigation, Data Curation, Writing - Original Draft, Writing - Review and Editing; Fabio Castellana: Data Curation, Formal analysis, Writing - Review and Editing; Adele Civino: Conceptualization, Methodology, Writing - Review and Editing, Supervision.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the “Giovanni Paolo II” Cancer Institute of Bari (Protocol code No. 656, approved on September 12, 2024). Written informed consent was obtained from all participants and/or their legal guardians prior to enrollment.

Consent for publication

Not applicable. This manuscript does not contain any individual person’s data in any form (including images or personal details).

Competing interests

The authors declare no competing interests.