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Updated: Aug 5, 2025

Osteoarthritis Pain Model Induced by Intra-Articular Injection of Mono-Iodoacetate in Rats
Published on: May 20, 2020
Evaluation of articular changes using a rat mono-iodoacetate-induced shoulder arthritis model by histology and
Shohei Ise1, Nobuyasu Ochiai1, Eiko Hashimoto1
1Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba City, Japan.
Abstract:
The rat mono-iodoacetate (MIA) arthritis model has been used in studies on the hip, knee, and ankle joints. Few studies have explored its utility in shoulder arthritis research, and none have evaluated the effects of time and different MIA doses on arthritis progression. Therefore, we developed a rat MIA shoulder arthritis model to evaluate articular changes through radiological and histological analyses. Sprague-Dawley rats (n = 108) were equally divided into groups that were intra-articularly injected with 0.5 mg of MIA (in 50 µL of purified water), 2.0 mg of MIA (in 50 µL of purified water), or purified water (50 µL; sham group). Throughout the study period, 18 rats (six per group) were evaluated by computed tomography and assessed using the Larsen's classification system; 90 rats were further evaluated histologically using the Osteoarthritis Research Society International scoring system. Computed tomography revealed that the groups injected with MIA developed arthritis and osteophytes 14 days after injection, which progressed temporally. The Larsen's grades worsened over time; at all time points, the scores were higher in the group injected with 2.0 mg of MIA than in the group injected with 0.5 mg of MIA. Furthermore, concurrent with the worsening Larsen's grades, the Osteoarthritis Research Society International scores also significantly increased over time; at all time points, they were higher in the group injected with 2.0 mg of MIA than in the group injected with 0.5 mg of MIA. Our rat MIA shoulder arthritis model revealed radiologically and histologically confirmed temporal and MIA dose-dependent arthritic changes.
Insights
This study establishes a rat shoulder arthritis model using mono-iodoacetate (MIA). Higher MIA doses and longer durations result in more severe, dose-dependent shoulder joint damage.
Area of Science:
- Orthopedics
- Rheumatology
- Animal Models
Background:
- The rat mono-iodoacetate (MIA) model is established for hip, knee, and ankle arthritis.
- Limited research exists on MIA-induced shoulder arthritis, with no studies on dose-dependency or temporal progression.
Purpose of the Study:
- To develop and validate a rat model of shoulder arthritis using MIA.
- To assess the impact of different MIA doses and time on arthritis progression in the shoulder joint.
Main Methods:
- 108 Sprague-Dawley rats received intra-articular injections of 0.5 mg MIA, 2.0 mg MIA, or saline (sham).
- Radiological analysis using computed tomography and Larsen's classification was performed at various time points.
- Histological analysis using the Osteoarthritis Research Society International (OARSI) scoring system was conducted on 90 rats.
Main Results:
- MIA injection induced shoulder arthritis and osteophytes within 14 days, with progression over time.
- Larsen's grades and OARSI scores were significantly higher in the 2.0 mg MIA group compared to the 0.5 mg MIA group at all time points.
- Both radiological and histological assessments confirmed temporal and dose-dependent arthritic changes in the rat shoulder model.
Conclusions:
- A reproducible rat MIA shoulder arthritis model has been established.
- The model demonstrates temporal progression and MIA dose-dependency for shoulder joint damage.
- This model is suitable for future research into shoulder osteoarthritis treatments.

