The Vicious Circle of Autonomic Dysfunction, Inflammation, and Pain in Osteoarthritis

Recent in vitro and animal studies suggested that the pathogenesis and progression of osteoarthritis (OA), a chronic degenerative and mild-inflammatory joint disease, may be affected by the autonomic nervous system (ANS). Under healthy conditions, the activities of the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS are well balanced. However, pathological conditions such as chronic stress, depression or rheumatoid arthritis are associated with a disturbance of this fine-tuned balance. We recently demonstrated that also patients in the late-stage of knee OA exhibit a sympathetic dominance indicated by significantly decreased heart rate variability (HRV). We detected associations of HRV parameters with increased perceived stress level (PSQ), cortisol/DHEA-S ratio as well as elevated systemic IL-6 concentration. One year after total knee arthroplasty (TKA), HRV parameters recovered again, although the levels did not increase to the values measured by healthy controls. Interestingly, although the levels of pain, cortisol/DHEA-S ratio, and serum IL-6 significantly decreased after TKA, they did not return to healthy levels and PSQ scores did not change at all. This might be explained by long-term manifestations of pain-inflammation-ANS interaction that did not yet recover one year after TKA. A second explanation might be that OA comorbidities such as hypertension, obesity, diabetes, or depression that are also associated with autonomic dysfunction and chronic mild systemic inflammation, maintain these symptoms. Thus, a vicious circle of autonomic dysfunction, inflammation and pain might occur in OA. Therefore, counteracting the autonomic dysfunction represents a promising treatment option for OA patients.