JIA is a well-known childhood disease with chronic pain being one of the symptoms. Objective quantification of changes in somatosensory processing such as QST in children with JIA aids in better understanding of pain in this disease. We show here that the German Research Network on Neuropathic Pain validated QST protocol is feasible in Dutch children aged 9 years and up, but not in children between 6-8 years of age.
Importantly, we identified that the pressure pain threshold is reduced at the inflamed and contralateral knee of JIA patients compared to healthy controls, whilst other pain thresholds did not differ from healthy control. Unexpectedly, the cold detection threshold was reduced only in the unaffected knee of JIA patients, while no significant differences were detected in the affected knee of JIA patients compared to controls. Possibly, the study population was too small to show significant CDT change in the ipsilateral knee. In conclusion, in our JIA patient population, Cold Detection Test and Pressure Pain Test were significantly different between JIA patients and healthy controls.
We detected a reduction in PPT at both the ipsi- and unaffected contralateral knee of JIA patients, indicating a generalized enhanced pain sensitivity (of hyperalgesic response) to pressure stimuli. Although others also have found that a unilateral inflammation induces a bilateral reduction in PPT in patients with JIA, we now confirm these findings with validated and standardized QST measures. The question rises why in both the affected and unaffected knee changes in PPT were observed. In adult rheumatoid arthritis patients, pain symptoms often arise before clinical manifestation of the arthritis, thus by analogy the possibility exists that some of JIA patients had subclinical inflammation at the contralateral knee causing the reduction in PPT. Alternatively, in JIA patients systemic inflammatory responses may cause bilateral reduction in PPT. For example, experimental systemic inflammation induced with an i.v. bolus with lipopolysacharide induced a generalized reduction in pressure pain threshold in healthy volunteers. Similarly, in patients with a unilateral neuropathy, pain sensory abnormalities, in particular for pressure pain threshold, were also observed at the non-affected site. It has been proposed that spreading of spinal glial activation and central sensitization induces bilateral alterations in sensory detection thresholds in preclinical mouse studies and pilot data in JIA patients. However, it remains to be determined whether such spinal changes occur in patients with JIA.
Importantly, the most frequent site of pain in JIA is the knee, and changes in sensory modalities specifically in the knee joint has not been studied in the context of JIA.
An earlier study has included QST measures of the knee of JIA patients, however, these knee QST datasets were combined with datasets of the ankle joint to compare active (n=17) and in-active joints (n=12). Whether the combined knee and ankle joint thresholds differed from that of healthy controls was not reported. In this study, we assessed sensory changes specifically at the knee of 21 healthy controls and 21 JIA patients with an active and inactive inflamed knee. We observed that only two sensory modalities (CDT and PPT) at the knee were affected compared to healthy control knee. No significant differences were observed between the inflamed and unaffected contralateral knee, similar to what was previously observed when knee and ankle joints were combined. An earlier study by Cornelissen et al. showed significant differences for all QST modalities when the inflammation of the ankle, knee or face was compared to the thenar eminence of a healthy control. However, QST data obtained from different joints is difficult to compare, as sensory thresholds of each joint are different. For example, the density of nerve endings at the thenar eminence is higher than at the knee, reducing the discriminatory sensitivity at the knee compared to the hand.
One limitation of this study is that the average duration of JIA was 6.2 years at the time of study. Thus the data represent sensory changes associated with chronic inflammation. Future studies could focus on sensory changes at the onset of rheumatic disease and how these changes correlate to pain levels during later stages of the disease. Also, in this population, medication was used extensively and ranged from NSAIDs to DMARDs. These drugs are known to have a dampening effect on pain, and as such could have affected pain VAS score and possible even QST measures
In conclusion, this study provides information that in Dutch children, the complete QST protocol is only feasible in the age group from 9 years and older, because children younger than 9 years were not able to complete the more extended DFNS QST test battery. In future studies, a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric arthritis population, with the purpose of identifying patients with persistent changes in somatosensory processing.