Quantitative characterization of a repeated acute joint inflammation model in rats.

1. Chronic pain owing to arthritis is a major clinical problem worldwide. To study the underlying pathological mechanisms of chronic pain and the effectiveness of different treatments, a number of experimental models have been developed over the years. 2. We introduced a new subchronic inflammatory model by repeated unilateral administration of carrageenan into the ankle joint of rats, and investigated the degree and the time-course of the oedema, and thermal and mechanical hyperalgesia. 3. Carrageenan (450 microg) was injected on three occasions (on days 1, 4 and 7), and the resulting oedema, thermal hyperalgesia (paw withdrawal test) and weight load were characterized in voluntarily walking rats daily for 15 days. The effect of diclofenac sodium (3 mg/kg orally daily for 15 days) was also determined. 4. Repetitive administration of carrageenan caused fluctuating oedema and pain responses, which did not normalize within 3 days. Exacerbated inflammatory oedema was observed after the second and third injections. Oedema and a decreased weight load of the inflamed paw were observed throughout the investigation period, and paw withdrawal thresholds to noxious thermal stimuli returned to baseline pre-carrageenan values from Day 13. 5. Oral diclofenac (3 mg/kg daily for 15 days) significantly decreased oedema within a few days (Day 3), whereas its anti-allodynic effect developed only several days later (Day 9). However, diclofenac at the applied dose did not influence the thermal hyperalgesia. 6. The results suggest that the repeated administration of carrageenan might be a suitable model for determining the effects of long-lasting treatment