Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.
Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, UK.
Pediatr Rheumatol Online J. 2019 Aug 27;17(1):60. doi: 10.1186/s12969-019-0360-3.
While pain is a common symptom in JIA patients, it remains unclear why some JIA patients develop ongoing or persistent pain. Complex clinical and social settings confound analysis of individual factors that may contribute to this pain. To address this, we first undertook a retrospective analysis of pain reports in a JIA patient cohort with the aim of identifying potential factors contributing to persistent pain. We then carried out an experimental laboratory study, using joint inflammatory pain behaviour in rodents, to validate the role of these factors in the onset of persistent pain under controlled conditions.
Patients: Retrospective analysis of anonymised pain visual analogue scale (VAS) scores and accompanying clinical scores from 97 JIA patients aged 13-19 (mean: 16.40 ± 1.21) collected over 50 weeks. Rats: Experimental study of pain behaviour following intra-articular microinjection of complete Freund's adjuvant (CFA) in adolescents (n = 25) and young adults (n = 43). Some animals (n = 21) had been previously exposed to joint inflammation in infancy or adolescence.
Patients: Cluster analysis of patient pain VAS scores revealed three trajectories over 50 weeks: consistently low pain (n = 45), variable pain (n = 30) and persistently high pain (n = 22). Number of actively inflamed joints did not differ in the three groups. High pain at a single visit correlated with greater physician global assessment of disease activity, while a high pain trajectory over 50 weeks was associated with more limited joints but fewer actively inflamed joints. Rats: Rodents administered ankle joint CFA also exhibit low, medium and high joint pain sensitivities, independent of joint inflammation. Prolonged inflammatory pain behaviour was associated with high background pain sensitivity, following joint inflammation at an earlier stage in life.
Both JIA patients and rodents differ in their individual pain sensitivity independent of the concurrent joint inflammation. Using experimental animal models allows us to isolate physiological factors underlying these differences, independently of social or clinical factors. The results suggest that a history of prior arthritic activity/joint inflammation may contribute to high pain sensitivity in adolescents with JIA.
疼痛是 JIA 患者的常见症状，但仍不清楚为什么有些 JIA 患者会持续或长期疼痛。复杂的临床和社会环境使分析可能导致这种疼痛的个体因素变得复杂。为了解决这个问题，我们首先对 JIA 患者队列的疼痛报告进行了回顾性分析，目的是确定可能导致持续性疼痛的潜在因素。然后，我们在啮齿动物中进行了一项实验性实验室研究，使用关节炎症性疼痛行为来验证这些因素在受控条件下引发持续性疼痛的作用。
患者：对 97 名 13-19 岁（平均：16.40±1.21）JIA 患者的匿名疼痛视觉模拟量表（VAS）评分和伴随的临床评分进行回顾性分析，这些评分在 50 周内收集。大鼠：在青少年（n=25）和年轻成人（n=43）中进行关节内完全弗氏佐剂（CFA）注射后的疼痛行为实验研究。一些动物（n=21）在婴儿期或青春期曾有过关节炎症的暴露。
患者：对患者疼痛 VAS 评分进行聚类分析，在 50 周内发现了三种轨迹：持续低疼痛（n=45）、疼痛波动（n=30）和持续高疼痛（n=22）。三组之间活跃关节的数量没有差异。单次就诊时的高疼痛与医生对疾病活动的总体评估相关，而 50 周内的高疼痛轨迹与关节受限更多但活跃关节炎症更少相关。大鼠：接受踝关节 CFA 注射的大鼠也表现出低、中、高关节疼痛敏感性，与关节炎症无关。在生命早期更早的关节炎症后，长期炎症性疼痛行为与较高的背景疼痛敏感性相关。
JIA 患者和大鼠在其个体疼痛敏感性方面存在差异，而与同时存在的关节炎症无关。使用实验动物模型使我们能够分离出这些差异的生理因素，而不受社会或临床因素的影响。结果表明，先前的关节炎活动/关节炎症史可能导致青少年 JIA 患者的高疼痛敏感性。
