Pain intensity in anatomical regions in relation to psychological factors in hypermobile Ehlers–Danlos syndrome

1 Introduction

The hypermobile subtype of Ehlers–Danlos Syndrome (hEDS) is a condition with a genetic background, which is estimated to affect 1 per 10,000–15,000 [1]. The hEDS diagnosis is based on clinical findings based on the international hEDS criteria [2]. Increased joint mobility, stretchable skin, and tissue fragility due to collagen defects, and a broad range of neurological, mucocutaneous, musculoskeletal, and gastrointestinal symptoms present with considerable variation in hEDS [2]. Musculoskeletal pain in two or more limbs for at least 3 months or chronic widespread pain is included in the diagnostic criteria [2]. Pain prevalence in hEDS patients ranges from 43 [3] to 97% [4] with the pain intensity showing a gradual increase over time in 75% of patients [4]. The pain is typically localized in several parts of the body [5,6].

Chronic pain conditions in general implicate complex, multidimensional developmental processes in which various psychosocial factors play a major role [7]. In patients with hEDS pain often impairs daily life and social interactions moderately to severely [8] and relates to lower health-related quality-of-life and greater psychological distress such as anxiety and depression, when compared to healthy individuals [9]. Most commonly diagnosed psychiatric disorders in hEDS are mood disorders and anxiety disorders [10]. It has been proposed that there is a relationship between anxiety, psychological dysfunction, and emotional problems, with indications that 70% of patients with hEDS report lifetime clinical anxiety [11]. It has been shown that 22.4% of patients with hEDS scored high on depression [12]. Further, high depressive symptomatology is significantly higher in highly anxious patients with hEDS [11].

A strong linear relationship between the number of pain sites with a decline in overall health, sleep quality, and psychological health have been shown in chronic conditions [13]. Pain at multiple locations is a risk indicator for developing depressive and anxiety disorders [14]. Patients with hEDS often experience chronic pain that can manifest across various anatomical regions [8]. The features of pain in hEDS are complex and poorly understood by clinicians [4] and the interrelations between anatomical region-specific pain in relation to psychological factors in hEDS have not been studied. Therefore, we investigated pain intensity in specific anatomical regions in relation to depressive symptoms and pain anxiety in patients with hEDS.

2 Methods

The study participants, all patients with a verified diagnosed hEDS, were recruited through a private clinic and the Finnish Ehlers–Danlos Association. Questionnaires were administered to 111 patients with hEDS: 17 received the questionnaires during a rehabilitation course at a private clinic, and 94 received theirs via mail. A total of 89 questionnaires were returned, yielding a response rate of 80%. Due to insufficient data or an incorrect diagnosis, eight questionnaires were discarded. The participants were provided with written information about the study.

This research project received ethics approval from the Research Ethical Committee at Helsinki University Hospital, Hospital District of Helsinki and Uusimaa (HUS), with reference number 312/13/03/2014.

3 Results

The number of anatomical regions in which participants reported pain ranged from 6 of 7 (3.7%) to 7 of 7 (96.3%). The total mean pain intensity reported in the study sample was 4.80 (SD = 1.65), while the most intense level of pain reported was 7.4 (SD = 1.87) on the NRS. The anatomical region for which the most intense pain was reported was the back (M = 5.99, SD = 2.24), followed by the lower extremities (M = 5.83, SD = 2.28), neck (M = 5.68, SD = 2.29) and upper extremities (M = 5.25, SD = 2.11). The mildest reported pain intensity was in the chest (M = 3.07, SD = 2.38) followed by the abdominal pain (M = 3.08, SD = 2.40) and head pain (M = 4.34, SD = 2.52). The pain intensity in specific anatomical regions is plotted in Figure 1. The NRS scores reported for different body regions differed significantly (p < 0.001).

Figure 1

NRS scores (0–10), including confidence intervals (95% CI), of hEDS patients for seven anatomical regions.

The study participants had a mean BDI score of 18.07 (SD = 11.26), with scores ranging between 0 and 57. Based on the diagnostic reference values for the BDI-II [17], 32 (39.5%) patients had minor depression (0–13), 18 (22.2%) had mild depression (14–19), 18 (22.2%) had moderate depression (20–28), and 13 (16.0%) were severely depressed (29–63). A positive correlation was found between the BDI scores and the NRS scores (r[76] = 0.366, p = 0.001).

The PASS-20 total scores – ranging between 3 and 89 – had a mean of 46.10 (SD = 18.29). There was a significant positive linear correlation between the PASS-20 and NRS total scores (r[76] = 0.347, p = <0.002; Table 2). Correlations between NRS, BDI, and Pass-20 are presented in Table 2 and Figure 2.

Figure 2

Pain intensity (NRS) in relation to depressive symptoms (BDI) and pain anxiety (PASS-20). The age- and gender-adjusted quadratic equation and grey bands show the 95% CI.

Analyses showed that mean total pain intensity related to depressive symptoms (r[76] = 0.359, p = 0.001) and pain anxiety (r[76] = 0.339, p = 0.002).

Analyses of relations between pain intensity in the specific body regions and psychological symptoms show that depressive symptoms are related to neck pain (r[76] = 0.274, p = 0.015), chest pain (r[76] = 0.274, p = 0.015), abdominal pain (r[76] = 0.292, p = 0.009), and pain in the lower extremities (r[76] = 0.331, p = 0.003).

Pain anxiety related to head pain (r[76] = 0.244, p = 0.031), neck pain (r[76] = 0.252, p = 0.026), chest pain (r[76] = 0.248, p = 0.028), back pain (r[76] = 0.282, p = 0.012), and pain in the lower extremities (r[76] = 0.273, p = 0.016).

Only pain in the upper extremities did not relate to depressive symptoms (r[76] = 0.219, p = 0.054) or pain anxiety (r[76] = 0.172, p = 0.132).

4 Discussion

The findings in our cross-sectional study highlight the relationship between pain intensity in specific anatomical regions and levels of depressive symptoms and pain anxiety and in patients with hEDS. The results show that the pain was widespread across anatomical regions. Second, the mean total pain intensity scores were related significantly to both depressive symptoms and pain anxiety. Specific findings were that strongest associations of depressive symptoms and pain intensity were in the abdomen and lower extremities. In contrast, pain in the upper extremities did not relate to depressive symptoms or pain anxiety.

The relations between abdominal pain intensity and depressive symptoms resemble findings documented in studies on patients with irritable bowel syndrome [25]. Additionally, it has been demonstrated that psychological distress can contribute to the onset of abdominal pain in hEDS [26]. In this regard, our findings suggest that there is a complex interplay between abdominal pain symptoms and psychological factors in hEDS.

Pain intensity in the lower extremities is related to depressive symptoms, which resembles results reported in studies on patients with rheumatoid arthritis [27]. Pain intensity in the lower extremities impacts the ability to move and perform daily life activities, and the loss of valued activities could explain the relations to depressive symptoms [28].

In most body regions, pain intensity is related to pain anxiety. This resembles findings in a meta-analysis on chronic musculoskeletal pain conditions by Martinez-Calderon et al. [29], which revealed that greater pain intensity associated significantly with higher level of pain-related anxiety. Further, in a study by Alter et al. [30], it was shown – using an exceptionally large unclassified sample of pain patients – that the extent of pain distribution impacts various clinical outcomes. Regarding our results, it seems that these associations also apply to hEDS.

Notably, the symptom burden is high in hEDS, which may increase anxiety-proneness [31]. It has been proposed that higher levels of anxiety contribute to the experience of pain [32]. Furthermore, pain catastrophising (i.e., anxiety) and fear of pain have been shown to impact the pain experience and its convergence with mental health [33]. These bidirectional relationships between experienced pain and anxiety may explain why total pain has the strongest correlation with pain anxiety in our study.

Pain in the upper extremities did not relate to psychological factors in this sample of hEDS patients, which differs from findings of Beleckas et al. [34], according to which patients with upper extremity conditions frequently experience anxiety and depression. This clinically interesting finding warrants further study.

The results show that the pain was intensive and widespread across body sites, which may be a significant contributing factor to depressive symptoms and pain anxiety in hEDS, given that hEDS represents a multifaceted syndrome with an extensive disease burden [35]. To the best of our knowledge, this study is the first to examine pain in specific anatomical regions in relation to psychological distress in the hEDS patient population.

5 Conclusion

We conclude that hEDS is a multidimensional syndrome that involves – in addition to pain occurring in multiple anatomical regions – psychological co-factors. A deeper understanding of behavioural factors and recognising the critical significance of pain intensity and pain location can equip healthcare professionals to develop suitable therapeutical interventions for patients with hEDS. Consequently, a multidisciplinary biopsychosocial treatment programme for patients with hEDS seems indicated. To the best of our knowledge, this study is the first to examine pain in specific anatomical regions in relation to psychological distress in the hEDS patient population.