Pain is a very common and sometimes limiting symptom in patients with juvenile idiopathic arthritis (JIA). Nonetheless, there remain many unanswered questions regarding pain perception in JIA and the neurobiology of pain in this disease. In this edition of The Journal, Leegaard, et al1 report their findings of lowered pain threshold in patients with JIA that add to our understanding of a fundamental aspect of this disease manifestation in JIA.
The disease pattern for JIA tends to follow a course of quiescent periods with disease activity flares superimposed. Some children have unrelenting disease activity that may be resistant to therapeutic interventions. Treatment of JIA is often complex and relies on medications, allied health interventions, and multidisciplinary expertise, ideally delivered in a coordinated manner in a predominantly ambulatory setting.
JIA may have a profound influence on children’s lives and their experience of pain may be central to this2,3. Studies have found that reduced quality of life and functional outcome (social, emotional, and physical), lowered mood, and poor sleep are all associated with higher levels of pain perception in JIA4,5,6.
Pain in JIA has historically been underreported, under-recognized, and underresearched, with clinical and research focus on inflammation, damage, and function. There are few specific or multidimensional and reliable pain assessment tools7, which has limited clinical research. Thus, the evidence base for pain management has traditionally relied upon extrapolation from adult medicine8. By enriching our understanding of the neurobiology of pain pathways in JIA, the predictive factors for those young people most vulnerable to pain, in conjunction with a focus on developing effective treatments, we will make inroads into one of the most significant symptoms for our patients with JIA.
What is known regarding the pain experience in JIA?
While there are many studies outlining the pain experience in adults with chronic arthritis, there has been until recently a paucity of information regarding the pain experienced by children and adolescents with JIA. Only 30 years ago, researchers suggested that children with JIA experience less pain than adults with comparable disease processes such as rheumatoid arthritis8. These findings were based on the pain measurement tools available at that time, which have since been refined, and this may have hindered the understanding of the pain experience in JIA, which is more prevalent than initially appreciated.
Children and adolescents with JIA experience pain commonly. Studies in JIA reveal a prevalence of pain between 50% and 86%, with many children having continuing pain over the course of their illness (50% at 1 year postdiagnosis and 40% at 5 years postdiagnosis)9,10. Pain is the most common symptom at presentation and at followup clinic visits, occurring > 85% of the time2,11. Even in the age of biologic disease-modifying antirheumatic drugs, pain remains the most common symptom for patients with JIA, with 76% of children reporting pain on > 60% of days despite treatment with methotrexate, tumor necrosis factor blockers, or combination therapy12.
The character of the pain tends to be in the mild to moderate range of intensity. However, up to 25% of children feel pain at a higher intensity than this11. Several studies over recent decades have attempted to describe the character of the pain experienced in JIA9,10,13. The most common descriptors are of a background, constant pain with a superimposed sharp component, as well as movement-induced incident pain15. A recent study reported 65% of young people with JIA have marked within-day differences in pain intensity (≥ 10 units on a 0–100 visual analog scale) and this affects quality of life14.
The cause of pain in JIA is somatic; however, there are other important pathogenic influences on a young person’s pain. These include psychological, genetic, psychosocial, familial models of pain, developmental stage, and chronological age, along with past experiences of pain7,8,16,17. These will all influence the pain experience for an individual young person. This biopsychosocial model of pain used more broadly within pediatric pain medicine is also very relevant in the context of JIA pain.
Additionally, in this era of advanced pharmacological therapies that have significantly influenced the disease course of JIA, there is now the potential effect of repeated soft-tissue needling that is often required for drug delivery. This results in repeated stimulation of nociceptors on a background of often daily persistent pain. Many also undergo repeated procedures such as venipunctures, magnetic resonance imaging scans with injectable contrast, and intraarticular injections. It is therefore important to optimize procedural pain management to minimize distress and prevent further central sensitization of the nervous system.
Pain neurobiology and predictors of pain in JIA
Several research studies have reported reduced pain thresholds in patients with JIA (with both active or quiescent joint disease) as well as evidence from the laboratory using cold pressor-induced pain that JIA patients have reduced pain tolerance17,18. Of interest, the lower pain threshold and tolerance correlated with increased pain report, possibly reflecting central sensitization and nociceptive pathway plasticity in the face of prolonged painful stimuli. Leegaard, et al1 report that children with JIA had a substantially lower pain threshold even in areas unaffected by arthritis. The researchers used a novel method: a digital pressure algometer on both articular and nonarticular anatomical locations. One particularly interesting finding was that the decreased pain threshold occurred without correlation to disease duration. That is, neurobiological changes were detected early after disease onset, reflecting possibly both physiological early central sensitization and psychological effects of persisting and fluctuating pain. These results add to knowledge of pain neurobiology in JIA and in particular how pain perception may be altered and pain threshold decreased. Further studies are needed to determine the mechanisms as well as predictive and risk factors, with the goal of improving identification of the most vulnerable patients and providing effective treatments.
A number of demographic and psychosocial factors may play a role in the pain experienced in JIA16. Sex may be important, although the evidence has been inconclusive2,16. Of note, several studies found females reported more pain than males, and those with polyarticular disease were at particular risk12,19. The age of the child or adolescent often has a role in the level of pain-reporting; this likely reflects the developmental stages and cognitive maturity regarding pain in the pediatric population. As children develop they are more able to localize the pain of a site such as a joint and to interpret it in the context of an ongoing illness such as JIA. However, the data are conflicting and a number of other studies have not shown age or sex to be a predictor of pain in patients with JIA12,16. A wide range of psychosocial variables have been studied and those found to influence the pain experience in JIA include emotional distress, daily stress, and mood changes7,20. Additionally, familial pain history, parental pain history, and how children with JIA cope with their pain (with catastrophizing a key factor) have all been shown to affect the pain experience in JIA6,20.
The presumption has been that disease activity in JIA should correlate well with the severity of the pain experienced. However, a number of studies found that disease activity predicted only a small to medium proportion of the pain experience in JIA7,16. Disease severity was recently found to be a significant predictor of higher intensity pain variability14.
Traditionally, the approach to JIA pain management has been to treat the active disease component of JIA, with the view that pain will cease or dramatically diminish thereafter. However, there is more to JIA pain management than merely suppression of synovitis. In the past decade we have seen an increased research base regarding the change in neurobiology for young people with JIA, and an increased understanding of persisting sensitivity to altered pain sensation beyond that of the period of active synovitis. Interventions have been extrapolated from other pediatric pain management and adult arthritis pain management approaches. There have been no clinical drug trials researching pain and JIA7. Thus, there are no evidence-based clinical guidelines for JIA pain management. Pain management predominantly involves a multimodal approach, ideally involving a multidisciplinary strategy from medical, nursing, and allied health professionals.
Multiple aspects of JIA pain neurobiology and clinical expression remain poorly understood. Reliable multidimensional pain assessment tools are under development. The study by Leegaard, et al1 clarifies several aspects of lowered pain threshold and the neurobiology and pain experience for young people with JIA. This interesting work assists in guiding our clinical practice and clinical research to look beyond pure JIA disease activity into the complex puzzle of the neurobiology, psychology, and social aspects that form the pain experience for each of our patients.