Osteoarthritis (OA) is the degradation of joint cartilage and bone, resulting from joint overuse and injury. The endocannabinoid system (ECS) is a molecular system that regulates bodily functions, including pain, inflammatory responses, and immune responses. Within the ECS, cyclooxygenase-1 (COX1), cyclooxygenase-2 (COX-2), and monoacylglycerol lipase (MAGL) function within a pathway that produces prostaglandins to signal pain. This study observed the differences in the amount of pain signaling proteins of interest (CGRP, MAGL, COX-1, and COX-2 ) present in knee samples of differing OA severity. It was hypothesized that OA samples that were assigned a higher grade of arthritic severity based on the Kellgren-Lawrence scale would have greater levels of these proteins, indicative of more pain being relayed in more severe cases of arthritis. Knee OA samples were collected and analyzed from patients receiving knee replacements (n=10) from June to August 2022. Immunohistochemistry techniques were used to identify and score proteins of interest (COX-1, COX-2, MAGL, and CGRP) within fixed tissue samples. When the presence of pain-signaling proteins were compared between samples of moderate to severe OA degradation, significantly more COX-2 and MAGL were found in more severe arthritic samples, leading to the hypothesis Enhanced Presence of Inflammatory Mediators MAG Lipase and COX-2 in Severe Osteoarthritis Mariam Hassan being supported. It was observed that drastic differences in protein levels based on arthritic severity were seen in the superficial cartilage of the sample.

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