Pararamosis, also known as Pararama-associated phalangeal periarthritis, is a neglected tropical disease primarily affecting rubber tappers in the Amazon region. It is caused by contact with the urticating hairs of the moth caterpillar, which resides in rubber plantations. The condition is marked by the thickening of the articular synovial membrane and cartilage impairment, features associated with chronic synovitis. Given the significance of synovial inflammation in osteoarticular diseases, in this study, the role of synoviocytes and their interactions with macrophages and chondrocytes are examined when stimulated by Pararama toxins. Synoviocytes and macrophages treated with Pararama hair extract showed an increased production of cytokines IL-6, IL-1β, and TNF-α, indicating a direct effect on these cells. In cocultures, there was a significant rise in inflammation, with levels of IL-1β, IL-6, and chemokines CCL2, CCL5, and CXCL8 increasing up to seven times compared to monocultures. Additionally, matrix-degrading enzymes MMP-1 and MMP-3 were significantly elevated in cocultures. Chondrocytes exposed to the extract also produced IL-6, CCL2, and CCL5, and in cocultures with synoviocytes, there was a notable increase in IL-6, CCL5, and CXCL8, as well as a doubling of MMP-1 and MMP-3 levels. These findings underscore the critical role of cell crosstalk in the inflammatory and catabolic processes associated with pararamosis and demonstrate how Pararama hair extract can influence factors affecting cartilage health, providing valuable insights into this condition.