Characterization of pain-related mechanisms and bone destruction in mild and severe monoiodoacetate-induced hip arthropathy in rats

Background This study aimed to characterize pain-related mechanisms and the bone-destructive environment in mild and severe monoiodoacetate (MIA)-induced hip arthropathy in rats, with particular focus on features relevant to rapidly destructive coxarthrosis. Methods Rats were divided into sham, low-dose MIA, and high-dose MIA groups ( n = 12 per group) and received intra-articular injections of saline, low-dose MIA, or high-dose MIA, respectively. Pain-related behaviors were assessed using von Frey and weight-bearing tests. Radiological and histological changes were evaluated using microcomputed tomography and the Osteoarthritis Research Society International scoring system. The proportion of calcitonin gene-related peptide (CGRP)-immunoreactive dorsal root ganglion (DRG) neurons and the number of ionized calcium-binding adaptor molecule 1 (Iba1)-immunoreactive microglia in the spinal dorsal horn were quantified immunohistochemically. Synovial mRNA expression of tumor necrosis factor-α ( Tnf-α ) and receptor activator of nuclear factor-kappa B ligand ( Rankl ), as well as osteoclast-like multinucleated cells in the femoral head, were also quantified. Results The high-dose MIA group showed significantly greater mechanical hypersensitivity and reduced weight-bearing capacity than the low-dose MIA and sham groups. This group also demonstrated more severe joint destruction, higher OARSI scores, a higher proportion of CGRP-immunoreactive DRG neurons, and an increased number of Iba1-immunoreactive microglia in the spinal dorsal horn. Synovial Tnf-α and Rankl mRNA expression levels were significantly increased in the high-dose MIA group compared with those in the sham and low-dose MIA groups. These changes were accompanied by an increased number of osteoclast-like multinucleated cells and bone resorption cavities compatible with Howship’s lacunae in the femoral head. Conclusions High-dose MIA-induced hip arthropathy was characterized by more severe pain-related behavior, a higher proportion of CGRP-immunoreactive DRG neurons, an increased number of Iba1-immunoreactive microglia in the spinal dorsal horn, and a more pronounced osteoclast-associated bone-destructive environment than low-dose MIA-induced hip arthropathy. These findings suggest that the high-dose MIA model exhibits several experimental features relevant to rapidly destructive hip disease.