Osteoarthritis (OA) and low back pain (LBP) are common musculoskeletal disorders in middle-aged and older adults, and account for around 17.0 % of years lived with disability worldwide [1]. Osteoarthritis is a long-term chronic degenerative disease of the joints, which is the result of aging and the weakening of the body's natural regulatory mechanism [2,3]. It mainly occurs in heavy, mobile joints, such as knee and hip [4]. The pathogenesis of osteoarthritis is not fully understood at present, and it is mainly related to age, obesity, inflammation, trauma and genetic factors [5,6]. The main problems affecting the quality of life of patients are the long-term chronic pain caused by the destruction of articular surface cartilage, hyperplasia of bone and synovial hyperplasia and inflammation of articular edge [7,8]. Our research is committed to seeking a new ingredient that can better relieve long-term chronic pain, reduce inflammation and improve quality of life in patients with osteoarthritis.

The main pathological changes of osteoarthritis are apoptosis of articular chondrocytes and progressive degradation of extracellular matrix (ECM) [9,10]. Overall, the pathologic mechanisms of osteoarthritis are complex and not fully understood. Studies on cytokines have long shown that cytokines play an important role in the occurrence and progression of osteoarthritis, among which IL-1β and TNF-α promote the destruction of cartilage and degradation of cartilage matrix in the pathological changes of osteoarthritis [11,12]. By inhibiting chondrocyte division and proteoglycan synthesis, stimulating the formation of matrix metalloproteinases (MMPs) and so on, it aggravates joint inflammation and leads to the occurrence of OA [13,14].

Inflammation, especially synovitis, has a significant effect on OA. Although central nociceptive pathways contribute to OA pain, crosstalk between the immune system and nociceptive neurons is central to inflammatory pain; therefore, new therapies might target this crosstalk [15]. A large body of literature has shown that OA synovium has a rich population of T cells and B cells compared to healthy controls [16,17]. Synovial macrophages as immune cells, macrophages polarize into M1 or M2 subtypes in the synovial tissue, synovial fluid, and peripheral blood of OA and are critical in the symptom and structural progression of OA [18]. Activated M1 macrophages play a key role in the inflammatory response of OA. The regulation of proinflammatory M1 in the joint cavity of OA into anti-inflammatory M2 macrophages may be a reasonable strategy for OA treatment [19].

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the first-line drugs for osteoarthritis patients to relieve pain and improve joint function [20]. Some patients are intolerant to NSAIDs or have little efficacy, so it is necessary to find new active substances to relieve the pain of osteoarthritis patients. Carveol is an endogenous metabolite [21]. Currently, studies have shown that Carveol has excellent anti-oxidative stress, anti-inflammatory and anti-neuroinflammatory pain effects [[22], [23], [24]]. No studies have explored its effect on osteoarthritis. Carveol's role in osteoarthritis has not yet been investigated. Using a co-culture system of macrophages and chondrocytes we studied changes in the immune system during the development and progression of osteoarthritis. Our study explored the role of CA in synovial macrophage action and chondrocyte inflammation.