Does osteoarthritis pain severity correspond more to inflammation or joint damage?

Abstract

Post traumatic osteoarthritis (PTOA) develops as a result of injury to the joint. This process involves progressive joint damage and chronic low-grade inflammation that leads to PTOA pain. This summer, I focused on damaging joint calcification and a serum macrophage-related inflammatory biomarker as potential mediators of PTOA pain. Progressive joint calcification is associated with sensory nerve growth, and soluble CD-14 is an activated macrophage biomarker associated with OA severity. Given that PTOA pain is related to both peripheral and central changes in the nervous system, we hypothesized that PTOA pain is more strongly correlated with circulating CD14 levels compared to joint calcification. We tested this hypothesis in lean and obese adult mice. 16-week-old male and female mice were fed either a high fat or control fat diet. At 36 weeks of age, mice were anesthetized and had a non-injury sham load or rapid compressive load applied to the knee to cause PTOA. Von Frey filament and Dynamic weight bearing tests were used to evaluate mechanical pain sensitivity before injury (baseline), and two- and four-weeks post injury. At 40 weeks of age, the mice were euthanized, and we collected knee joints and serum. We used micro-computed tomography to quantify joint calcification, and we quantified serum CD14 using an enzyme linked immunosorbent assay. At baseline, diet did not alter pain sensitivity. Pain sensitivity increased two weeks after both compression injury and sham loading to a similar level in lean and obese mice. We are completing the four-week post injury data analysis, and we have collected all samples to measure serum CD-14 and joint calcification. We will compare the increase in pain sensitivity to serum CD-14 concentration and joint calcification volume to test our hypothesis.