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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
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Arthritis Research & Therapy

ISSN: 1478-6362

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