Pain Intensity and Trajectory Following Intra-Articular Injection of Mono-Iodoacetate in Experimental Osteoarthritis: A Meta-Analysis of In Vivo Studies

OBJECTIVE: Although most frequently used in experimental osteoarthritis (OA) pain induction, intra-articular mono-iodoacetate (MIA) injection lacks concluded references for dose selection and timing of intervention. Herein, we aimed to compare the pain intensity of rats induced by different doses of MIA and explored the trajectory of pain. DESIGN: PubMed, Embase, and Web of Science were searched up to June 2021 for literatures involving MIA experiments investigating OA pain. Pain intensity was measured based on weightbearing distribution (WBD) and paw withdrawal thresholds (PWT), and the pain trajectory was constructed by evaluating pain intensity at a series of time points after MIA injection. A conventional meta-analysis was conducted. RESULTS: A total of 140 studies were included. Compared with saline, MIA injections caused significantly higher pain intensity for WBD and PWT. Dose-response relationships between different doses of MIA and pain intensity were observed (P-for-trend<0.05). A pronounced increase in pain occurred from day 0 to day 7, but the uptrend ceased between day 7 and day 14, after which the pain intensity continued to rise and reached the maximum by day 28. CONCLUSIONS: Pain intensity after intra-articular MIA injection increased in a dose-dependent manner and the pain trajectory manifested a specific pattern consistent with the pathological mechanisms of MIA-induced pain, providing possible clues for proper dose selection and timing of specific OA pain interventions.