Introduction
Pediatric rheumatic diseases (PRDs) are a group of chronic inflammatory conditions characterized by periods of disease flare-ups and often accompanied by pain [
1]. Pain in PRD is a common problem, with a prevalence up to 86% in children with juvenile idiopathic arthritis (JIA) [
2,
3]. Adolescents with pain reported experiencing reduced levels of physical functioning compared to patients with either mild or no pain, and they reported a significantly higher school absenteeism over the previous 6 months [
4]. Acute musculoskeletal pain in PRD can often be attributed primarily to local inflammation; therefore, an anti-inflammatory treatment regime is a key therapeutic feature [
5]. However, acute pain can progress into chronic musculoskeletal pain (CMP), even if the disease activity score is low [
6,
7].
Once musculoskeletal pain becomes chronic, it often persists into adulthood [
1,
8‐
10]. Children with CMP experience high levels of stress and are prone to anxiety and depression, which can in turn lead to increased pain and disability [
11‐
15]. In addition, children with CMP often report sleep difficulties, including a lack of refreshing sleep and increased fatigue, further disrupting their social and academic development [
4,
16‐
20]. Moreover, the impact of CMP is not confined to the individual patient, but can extend to the entire family and can have significant societal costs [
21‐
24].
Pain can negatively influence our behavior, activity, and participation; although this might be initially helpful, it can lose purpose if the pain becomes chronic. Acute pain is induced by local inflammation or injury. After that, peripheral and central sensitization contributes to an amplification of a new pain stimulus [
25]. Finally, endogenous pain modulatory pathways determine pain responses by the influence of attention, suggestion, expectation, stress, anxiety, context and past experience [
25]. While most pharmacological interventions are targeted on treatment of inflammation, alleviation of chronic pain might need another approach [
3,
6,
7,
16]. Several studies found that in addition to biological processes, psychosocial factors such as coping and cognitive health beliefs can determine the experience and impact of chronic pain, giving rise to the so-called biopsychosocial model [
15,
21,
26]. Expanding our knowledge beyond pharmacological solutions to include non-pharmacological interventions, such as psychological or exercise-based interventions, may, therefore, provide a promising means to alleviate pain and improve functioning in children with PRD.
Psychological therapies and exercise-based therapies have been shown to be beneficial for children with widespread chronic pain, who did not have PRD [
27‐
30]. These therapies have also been shown to exert modest beneficial effects in adults with rheumatic disease [
31]. In their review published in 2013, Cunningham and Kashikar-Zuck proposed that a multidisciplinary approach consisting of carefully selected pharmacological and non-pharmacological interventions based upon a biopsychosocial framework may provide the most effective approach to treating pain [
31].
Although non-pharmacological therapies may represent a promising addition and/or alternative to pharmacological therapies for alleviating chronic pain, evidence with respect to using non-pharmacological therapies for CMP in children and adolescents with PRD is extremely limited. In this review, the aim is to provide an overview of published non-pharmacological therapies for CMP in patients with PRD. This overview may serve as a stepping stone for future research and for the implementation of non-pharmacological therapies in clinical practice.
Methods
In our review, both randomized controlled trials (RCTs) and non-randomized controlled trials were eligible. The primary outcome measure was pain intensity, and the secondary outcome measures were functional disability and quality of life. We performed a systematic search of PubMed (both MEDLINE-indexed and PMC-archived items), Embase (Scopus), PsycINFO, and the Cochrane Library, with no date or language restrictions. The search terms included terms related to musculoskeletal pain or dysfunction, non-pharmacological treatment modalities, children, and pediatric rheumatic diseases. In addition, the reference lists of the retrieved papers were manually cross-referenced, and Scopus was used to search for additional relevant studies. The following inclusion criteria were used: (1) children 5–18 years of age with PRD and chronic musculoskeletal pain (defined as ≥ 3 months in duration) not associated with active disease; (2) it concerned primary research and was available in full-text; (3) the study included at least one non-pharmacological intervention arm such as exercise, physiotherapy, cognitive behavioral therapy (CBT), occupational therapy, biofeedback, or complementary and alternative medicine; and (4) the study outcomes included pain intensity. Exclusion criteria were: (1) Treatment arm with < 5 patients at the end of treatment; (2) studies on complex regional pain syndrome (CRPS); and (3) CMP associated with a malignant disease process.
The methodological quality of each included study was independently assessed by two authors (LNN and MMN) based on the Cochrane risk of bias tool, and the quality of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach [
32]. GRADE was developed to assess pooled data from studies in comparable settings, with comparable outcome parameters. In our review, however, the studies were separately assessed due to the limited numbers of studies available and the heterogeneity among these studies. Quality of evidence was categorized as very low, low, moderate, or high [
32].
Conclusions
Both psychological and exercise-based interventions have been shown to have modest beneficial effects on CMP in PRD. Moreover, non-pharmacological therapies are not associated with side effects. When pharmacological therapy is insufficient to alleviate pain in PRD, non-pharmacological therapies may serve as a suitable alternative and/or addition for reducing CMP and improving function. Importantly, chronic pain and acute pain may be etiologically different in PRD, and future studies should take this difference into account to identify the optimal therapeutic window for non-pharmacological approaches. Finally, studies are needed that specifically investigate chronic pain in PRD and are designed to improve social participation in children with PRD-related chronic pain, particularly with respect to the long-term effectiveness of these interventions.