Chronic Pain and Oxidative Stress in Knee Osteoarthritis: Role of Sulphurous Mud-Balneotherapy

The literature demonstrated the involvement of oxidative stress in the osteoarthritis (OA) pathogenesis and the antioxidant effect of sulphurous mineral waters. Thus the objectives of the study were to investigate the impact on symptoms and quality of life and a possible antioxidant action of sulphurous mud-balneotherapy in 38 patients suffering from Knee OA admitted to Telese spa (Telese Terme, Benevento-Italy). 20 subjects (group A) did not take any NSAIDs or other drugs for gonarthrosis, 18 subjects (group B) were in treatment with ibuprofen administered orally. All patients have submitted to one cycle of mud-balneotherapy for 2 weeks by using sulphurous mineral water. Before and after the treatment in groups A and B were measured: VAS scores for pain during joint movement and the morning stiffness; Algofunctional Lequesne index; and plasma [ROMs] levels using the d-ROMs test. Sulphurous mud-balneotherapy induced a significant (p<0.05) reduction of the VAS score symptoms compared to basal values both in group A and in group B, with improvement of quality of life as shown by Lequesne index; moreover it was observed a significant (p<0.05) decrease of plasma [ROMs] levels. In conclusion this study suggests that the sulphurous mud-balneotherapy could represent an important component of the overall strategy to treat knee OA. Introduction Osteoarthritis (OA) is degenerative joint disease caused by an imbalance between anabolic and catabolic processes in favor of the latter (1). Several molecules are involved in the pathogenesis of OA. Among them, Matrix MetalloProteinases (MMPs), which act on the collagen fibers and core protein of proteoglycans, have a crucial role (2). In addition, Tumor Necrosis Factor-α (TNF-α), and Interleukins (ILs), including IL-1, IL-6 and IL-17, concur to amplify cellular inflammatory response and accelerate the progression of joint tissues damage (3). An important role in the pathogenesis of the OA is also played by oxidative stress generated by the accumulation of Reactive Oxygen Species (ROS), and by over-production of Nitric Oxide (NO) released by the inflammatory synovial cells and chondrocytes (4-6). All the abovementioned factors contribute to produce and/or exacerbate symptoms and signs of OA, such as pain during joint movement, difficulty in the daily activities and morning stiffness (7). The goals of OA treatment include alleviation of pain, slowing the progression of the anatomical damage and reduction of the anxiety-depressive symptoms caused by physical disability, and ultimately improving the quality of life of patients (8,9). Nowadays, available therapeutic strategies include drugs, physical rehabilitation, surgical intervention and spa (salus per aquam) therapy (10,11). It has been demonstrated that spa therapy (12-14) is effective in reducing pain and anxiety-depressive symptoms and increasing joint functional capacity in OA, including knee OA (or gonarthrosis), which is the most common degenerative joint disease (15-17). The spa therapy includes a number of therapeutic approaches such as bath therapy, hydropinotherapy, caves therapy and mud-balneotherapy (18). Mud-balneotherapy is effective in reducing the number and the doses of analgesic and/or anti-inflammatory nonsteroidal anti-inflammatory drugs (NSAIDs), usually used in rheumatic diseases (12). Moreover, it has been proven to ameliorate quality of life of OA patients (13,15). Many studies have investigated on systemic and local effects of mud-balneotherapy in osteoarthritic patients in terms of mechanism of action and efficacy (6,19). It was suggested that such treatment is able to modify plasmatic levels of inflammatory and immune mediators, such as IL-1, PGE2 and TNF-a, and to activate the diencephalic–pituitary–adrenal axis by increasing the production of ACTH and endogenous opioids (such as β-endorphin) (2024). Importantly, this seems to translate in analgesic and antiinflammatory effects and to improve the patients mobility.