Intra-articular polyacrylamide hydrogel (PAHG; Arthramid) is increasingly used as a treatment for osteoarthritis (OA) in horses, but the mechanism of action remains unclear. The objectives of this study were to determine whether there was any impact of this material on synovial neurons or changes to inflammatory cell populations or their function.
Samples of synovial membrane were obtained from the forelimb fetlock and carpal joints of 13 Thoroughbred horses previously treated with PAHG, obtained at postmortem after being euthanased for reasons unrelated to the study. Gross changes to the cartilage surfaces and synovial histopathology were assessed and graded. Immunohistochemistry was used to identify cells of the macrophage lineage and synovial nerves.
Where horses had received PAHG treatment, intimal thickening and macrophage infiltration into the subintima was observed. When immunostaining for sensory nerves in the synovium was quantified and compared, there was no effect of treatment on number, size or quantity of synovial sensory nerves. This was consistent with findings in vitro, where no direct or indirect toxic effects of PAHG on neurons was observed. However, PAHG induced equine monocyte-derived macrophages to produce the anti-inflammatory cytokine, IL-10, but not the pro-inflammatory cytokines, IL-1β, TNF-α and IL-6. This was consistent with the adoption of the M2 phenotype.
This study indicates that PAHG does not appear to cause direct toxic effects to neurons. However, after it is taken up into the synovium by macrophages and type A synoviocytes, this material may induce the anti-inflammatory M2 phenotype with the release of IL-10 and other anti-inflammatory factors. Further studies are required to confirm levels of these factors in vivo; and investigate comparisons between PAHG and intra-articular corticosteroids in different forms of joint disease.