Effects of very early arthritis on pain, behavior, and hippocampal TNF/BDNF in rats

Background Juvenile idiopathic arthritis (JIA) is the most common childhood chronic arthritis, and pain may persist despite controlled inflammation, potentially due to central sensitization. This study aimed to evaluate the effects of very early-onset arthritis on pain, behavior, and cognition using a collagen-induced arthritis model in juvenile rats. Methods Thirty-six three-week-old male Wistar rats were divided into control, sham (saline), and arthritis (type II collagen with incomplete Freund’s adjuvant) groups. Disease severity was monitored via joint thickness and VAS. Pain (hot plate, Randall-Selitto), behaviors (EPM, MFST), and cognition (PAT) were assessed. Locomotor activity was assessed. Joints were analyzed histologically (H&E); hippocampal BDNF and TNF-α were examined immunohistochemically. Results Arthritis severity progressed over six weeks, with increased joint thickness and VAS scores in the arthritis group ( p < 0.05). Mechanical hyperalgesia showed a paw- and time-dependent pattern, with earlier changes in some paws and more consistent reductions during the late phase (weeks 4–6). Locomotor activity did not differ among groups, indicating no motor deficits. The arthritis group exhibited greater anxiety (EPM, p = 0.001) and depression-like behavior (FST, p = 0.004), while cognition (PAT) remained unaffected. Hippocampal TNF-α increased, whereas BDNF was unchanged. Conclusion Very early-onset arthritis is associated with mechanical hyperalgesia and emotional disturbances, accompanied by hippocampal TNF-α alterations, and exhibits features consistent with central sensitization, without significant effects on cognition or hippocampal BDNF expression. Impact Early juvenile arthritis showed mild severity with delayed mechanical hyperalgesia. Thermal hyperalgesia and locomotor deficits were not observed in arthritic rats. Hippocampal TNF-α increase was linked to anxiety and depression-like behaviors. Hippocampal BDNF levels remained stable, suggesting intact learning processes.