Table 1.
Common OA models and reported pain behaviors.
| Type | Model (Onset of Pathology) | Pros/Cons | Pathological Findings | Behavioral Assay (Pain Response Onset) | Findings | Molecular Pathogenesis Identified |
|---|---|---|---|---|---|---|
| Surgical | DMM (4 wk) |
Mimics human post-traumatic OA, slow disease progression and mild cartilage damage, useful in assessing therapies. Need specially trained surgeon, risk of infection. |
-Cartilage degradation -Synovial hyperplasia -Bone sclerosis -Osteophyte formation |
von Frey (4 wk), incapacitance (4 wk), hot plate (8 wk), LABORAS (8 wk), gait abnormality (10 wk) |
Pain response is progressively induced in early phase. Most representative method: von Frey |
Loss of PKCδ exacerbates pain in DMM. ADAMTS-5 inhibition attenuates pain in DMM. Knockout of RANKL inhibits pain in ACLT mice. Knockout of Netrin-1 inhibits pain in ACLT mice. |
| MNX (2 wk) |
More rapid disease onset and higher damage in the joint compared with human disease, useful in assessing therapies. Need specially trained surgeon, risk of infection. |
von Frey (1 wk), incapacitance (3 d), cold plate (5 wk) |
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| ACLT (2 wk) |
von Frey (1 wk), incapacitance (1 wk), hot plate (4 wk), rotarod (4 wk), LABORAS (1 wk), gait (8 w) | |||||
| Chemical | MIA (3–7 d) |
Easy local injection method, rapid induction of severe joint degeneration, useful for studies in pain behavior. More difficult to translate to human setting. |
-Inhibition of glycolysis and disruption of chondrocyte metabolism -Cartilage degradation -Synovial hyperplasia -Osteophyte formation |
von Frey (1 wk), incapacitance (3 d), hot plate (6 d), rotarod (15 d), gait (6 d), LABORAS (14 d) |
Pain response is induced rapidly within a week post-injection. Most representative methods: von Frey and incapacitance |
Neutralization of CCL-17 ameliorates pain in CIOA. Increase of IRF-4, CCL-17 in CIOA. |
| CIOA (1–4 wk) |
Most rapid progression, useful in assessing therapies. More difficult to translate to human setting. |
-Cartilage degradation -Osteophyte formation |
von Frey (1 wk), incapacitance (1 wk), hot plate (1 wk) | |||
| Spontaneous/noninvasive | STR/ort (8–16 wk) |
Might mimic primary human OA, no specially trained personnel required. Long period for the development of OA, high variability of the disease phenotype and incidence. |
-Cartilage degradation -Osteophyte formation |
von Frey (no difference), gait (20 w), cold plate (no difference) |
Pain response does not show significant variation with age. | STR/ort mice do not show any signs of pain even when treated with the opioid antagonist naloxone. |
| Mechanical joint loading (1 wk) |
Noninvasive, suitable to study the effects of mechanical loading and intra-articular fracture, rapid induction of severe joint degeneration. Need specialized equipment. |
-Cartilage degradation -Bone sclerosis -Osteophyte formation |
von Frey (2 wk), incapacitance (4 wk), hot plate (no difference), rotarod (5 wk) |
Pain response is progressively induced in early phase. | Anti-NGF alleviates pain in mechanical joint loading model. |
DMM, destabilization of medial meniscus; MNX, medial meniscal transection; ACLT, anterior cruciate ligament transection; MIA, monosodium iodoacetate; CIOA, collagenase-induced arthritis; OA, osteoarthritis; LABORAS, laboratory animal behavior observation registration and analysis system; d, day; wk, week(s); PKCδ, protein kinase C delta; ADAMTS-5, a disintegrin and metalloproteinase with thrombospondin motifs 5; RANKL, receptor activator of nuclear factor kappa-B ligand; CCL-17, chemokine (c-c motif) ligand 17; IRF-4, of interferon regulatory factor 4; NGF, nerve growth factor.