Monosodium Iodoacetate Induces Knee Osteoarthritis in Rats in a Dose- and Time-Dependent Manner

Knee osteoarthritis (KOA) is indeed a major global health issue, characterized as the most common form of osteoarthritis. It affects millions of people worldwide, leading to joint pain, stiffness, and functional limitations. As life expectancy increases and populations age, KOA's impact on quality of life and public health systems becomes more pronounced. Our objective was to evaluate pain-related behaviors, tibial cartilage pathology, and inflammatory factor expression levels in rats following different doses and administration times of monosodium iodoacetate (MIA) to explore its effects on KOA.

The rats were allocated into two groups: an experimental group and a control group. In the experimental group, MIA was administered as a single intra-articular injection into the left knee joint to induce KOA. The dosage varied between 0.5 mg and 2.0 mg. Following the injection, assessments were conducted on days 3, 5, 7, 14, 21, and 28 to evaluate knee circumference, pain-related behavior, tibial cartilage pathology, and the expression levels of IL-1β and IL-10.

The knee joint diameters expanded in a dose- and time-dependent manner, paralleled by corresponding reductions in MIA-induced paw withdrawal threshold (PWT) and weight-bearing distribution (WBD), both of which followed similar dose- and time-dependent patterns. Compared with controls, MIA-treated rats exhibited significantly heightened defensive behaviors (eg, paw licking, retraction), confirming successful inflammatory pain induction. Pain intensity analysis revealed lower pain scores in the 0.5 and 1.0 mg MIA groups relative to 1.5 and 2.0 mg groups across the study. Pain severity escalated sharply from day 0 to 7, stabilized until day 14, and peaked again at day 28. Histologically, the 1.5 and 2.0 mg MIA groups demonstrated early-stage KOA pathology (days 5-20), characterized by chondrocyte cloning and matrix disorganization, followed by mid-stage features (days 21-27) including localized cartilage defects, surface irregularities, hypocellularity, and vascular infiltration. By day 28, late-stage KOA hallmarks emerged, such as widespread cartilage degeneration, subchondral bone exposure, and peripheral osteophytes. These histological findings aligned with behavioral pain outcomes and ELISA results, collectively illustrating synchronized progression of inflammatory and structural pathology across all assays.

The severity of pain, the extent of articular cartilage degeneration, and the level of inflammatory response following intra-articular MIA injection progressively worsened in a dose- and time-dependent fashion. In the MIA group, early-stage KOA cartilage pathology was observed between days 5 to 20 post-injection. By day 21, cartilage lesions progressed to mid-stage KOA cartilage, and by day 28, they advanced to late-stage KOA cartilage. The pain trajectory corresponded with the pathological features of MIA-induced KOA, offering valuable insights into optimal dosing and timing for targeted KOA pain management interventions.