Human patients and rat models of juvenile idiopathic arthritis have unique thresholds of pain sensitivity, which is most likely related to their history of disease activity and joint inflammation rather than their current arthritic symptoms, a study has found.
The study, “The pain trajectory of juvenile idiopathic arthritis (JIA): translating from adolescent patient report to behavioural sensitivity in a juvenile animal model,” was published in Pediatric Rheumatology.
Juvenile idiopathic arthritis (JIA) comprises a group of chronic inflammatory conditions in children that affect the joints, causing swelling, stiffness, and pain.
While pain is one of the most prevalent features of JIA, affecting more than 70% of patients, it is still unclear why 10%–20% of individuals progress to develop persistent pain within five years after diagnosis and others do not.
One possible explanation is that each individual has a unique threshold for pain, which may depend on certain biological and psychosocial factors, including age, gender, disease duration, anxiety, depression, and stress. When combined, these factors “may contribute to this [pain] sensitivity and the development of persistent pain,” the researchers, from University College London (UCL), said.
Their study set out to identify and validate biological factors that might explain the development of persistent pain in some individuals with JIA, using a combined approach based on data from human patients and animal models of the disease.
In the first part of the study, the investigators performed a retrospective analysis of anonymized pain reports to identify possible biological factors that could play a role in pain sensitivity.
These reports were collected over a period of 50 weeks from a group of 97 JIA patients from 13 to 19 years old. Pain was determined based on the visual analogue scale (VAS). Besides pain reports, the investigators also reviewed the patients’ clinical data.
In the second part of the study, the researchers performed a series of experiments in rats to validate biological factors previously identified in the retrospective analysis.
Experiments involved triggering joint inflammation in the animals at different time-points and monitoring their behavior. To trigger inflammation, the investigators injected complete Freund’s adjuvant (CFA) — a solution that boosts an immune response — into the joints of 25 adolescent and 43 young adult rats. In a sub-group of 21 rats, joint inflammation was triggered more than once, either during their infancy or adolescence.
The retrospective analysis based on pain reports revealed that patients followed one of three pain trajectories: their pain remained consistently low (45 patients), varied (30 patients), or was constantly high (22 patients).
The current number of inflamed joints was identical in individuals from all three pain trajectories. However, patients in the persistent pain group tended to have a higher number of limited joints (joints that had lost mobility) and fewer actively inflamed joints.
“[W]hile active arthritis is less likely in patients with high pain, these patients had more swollen and limited joints, suggesting that prior arthritic activity may influence the progression of pain,” the researchers said.
Experiments performed on rats showed that animals that had been treated with CFA had different thresholds of pain sensitivity, regardless of current joint inflammation. However, the rats tended to be more sensitive to pain when joint inflammation had been triggered more than once.
“As predicted from the patient data, a prior bout of inflammation exacerbated pain, measured by weight bearing, but only in animals with higher baseline levels of pain sensitivity,” the researchers wrote.
“A significant number of both JIA patients and rodent models have pain that is persistently higher or more prolonged than other individuals of the same age, sex, and arthritic activity,” they said. “The results support the hypothesis that prior, rather than current, arthritic activity may be an explanatory factor for those individuals with a high sensitivity to inflammatory pain.”