Skip to main content

Table 3 Summary of the in vivo results using the MIA rat model

From: Randomized controlled studies on the efficacy of antiarthritic agents in inhibiting cartilage degeneration and pain associated with progression of osteoarthritis in the rat

MIA model Results
  Trial 1: systemic delivery Weight bearing (significant differences; h) Histopathology (n = 3)a
  Drug (daily) Dose (s.c.) (mg/kg) Number of animals 7 days 14 days 21 days 28 days Cartilage Bone
1 Vehicle saline 5 10     Term 4.7 Severe
2 Clonidine 0.1 10 1, 5, 24 1 1 1, 3 4.7 Severe
3 Fluocinolone 0.002 10    BLb, 1   3.0 Minimal
4 Morphine 6 10 1, 3, 5 1 BL, 1, 3 1, 3 N/A N/A
1H Vehicle Saline 5 ml/kg 3 Term N/A N/A N/A 4.7 Severe
2H Vehicle Saline 5 ml/kg 3 N/A Term N/A N/A 5.0 Severe
3H Vehicle Saline 5 ml/kg 3 N/A N/A Term N/A 4.7 Severe
  Trial 2: systemic delivery (n = 10) Digital Randall-Selitto (significant differences; h) Histopathology (n = 3 or 4)
  Drug (daily, unless indicated) Dose (mg/kg) Route (ml) 7 days 14 days 21 days 28 days Cartilage matrix Total joints
1 Vehicle saline N/A s.c. (5)    1, −5   4.5 ± 0.5 14.3 ± 1.1
2 Clonidine (weekly)c 0.1 s.c. (5) 1, 3, 5 1, 3, 5 3 1, 3, 5 3.7 ± 0.3 11.7 ± 0.9
3 Tacrolimus 0.3 i.p. (1)    Pretrtd   3.8 ± 0.6 11.5 ± 1.7
4 Tacrolimus 0.6 i.p. (1)    1   3.8 ± 0.6 10.3 ± 2.1
5 Curcumin 50 p.o. (5) 1   Pretrtd   5.0 ± 0.0 14.5 ± 0.3
6 Fluocinolone 0.01 s.c. (5)   5e    3.3 ± 0.8 9.3 ± 2.5
  Trial 3: articular delivery (n = 10) Digital Randall-Selitto test (significant differences; h) Histopathology (n = 3)
  Drug (weekly) Dose (μg) Route (30 μl for i.a.) 7 days 14 days 21 days 28 days Cartilage matrix Total joints
1 Vehicle saline N/A i.a.      2.7 ± 1.5 5.7 ± 3.8
2 Clonidine 100 μg/kg s.c. 1, 3, 5 1, 3 1, 3 1, 3 3.7 ± 0.9 10.7 ± 2.8
3 Clonidine 4.5 i.a. 1     3.0 ± 1.1 8.7 ± 3.3
4 Tacrolimus 0.03 i.a.      5.0 ± 0.0 13.3 ± 1.7
5 Fluocinolone 0.015 i.a. 1    −24 3.3 ± 1.2 10.3 ± 2.7
6 Meloxicam 100 i.a. 1 3    1.0 ± 0.0 3.0 ± 1.2
7 Tranilast 0.5 i.a. 1, 3 1 1   5.0 ± 0.0 14.3 ± 0.3
8 Triamcinolone H 150 i.a. 3 1 Pretrtf −24 3.3 ± 0.9 8.3 ± 2.6
  1. BL baseline, i.a. intraarticular, i.p. intraperitoneal, p.o., per oral, s.c. subcutaneous delivery
  2. The details of the related studies and results are provided in Additional file 1. Shown are hours after drug delivery where a statistically measurable effect (p ≤ 0.05) was observed on weight bearing or mechanical hyperalgesia compared with the pretreatment baseline of that day, unless noted otherwise. Negative values indicate decreasing of threshold (e.g., −24 = worse at 24 h). “Pretrt” refers to an effect on pain that was measurable before the dosing for that particular day
  3. For histopathology, scores approach 0 with improvement. The femoral cartilage degeneration score and the three-zone sum of the tibial cartilage degeneration scores (mean of three levels) were summed to create a total cartilage degeneration score (shown). The mean osteophyte score for each joint was added to this value to create a total joint score with matrix. Additional measures of tibial cartilage, bone and synovial changes, and details of statistical analysis are provided in Additional file 1
  4. aGroups 1–3 necropsy on day 29; group 1H necropsy on day 7, group 2H on day 14, and group 3H on day 21
  5. bSignificant difference in weight-bearing score on day 21 compared with vehicle control–treated rats
  6. cWeekly clonidine showed significant effects on the pretreatment joint compression threshold compared with pretreatment vehicle alone, observed on days 7, 14, 21, and 28
  7. dTreatment resulted in a significant increase in pre-treatment joint compression thresholds compared with pretreatment on day 7
  8. eSignificant decrease in joint compression threshold compared with vehicle controls; no effect compared with day 7 pretreatment baseline
  9. fSignificant decrease in joint compression threshold compared with day 7 pretreatment baseline