TNF and synovitis: Synovitis mechanisms, including the release of pro-inflammatory mediators such as tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1β), monocyte chemoattractant protein 1 (MCP1), and IL6, are known to sensitize and activate nociceptors, lowering the threshold required for pain activation and leading to pain sensitization [26,27,28].