Osteoarthritis patients exhibit an autonomic dysfunction with parasympathetic deficiency and sympathetic dominance
Authors:   , Sohn Rebecca 
Published: October 2024

Osteoarthritis (OA) is a complex, multi-factorial disease that leads to degenerative and inflammatory processes in joint tissues, resulting in whole joint dysfunction and pain. In addition, this condition is accompanied by mild chronic inflammation. Until now, there is no causal treatment for OA and disease management is limited to symptomatic therapy options, such as pain medication. Consequently, patients at the late stage of the disease finally undergo total joint replacement surgery. One reason for the lack of causal treatment strategies is most likely that OA research has long focused on pathological alterations only at the joint level. However, also systemic factors, such as the autonomic nervous system (ANS), may alter OA pathophysiology. The ANS comprises two major branches, the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). In a healthy organism, sympathetic and parasympathetic effects are optimally balanced, providing homeostasis for various physiological functions, such as heartbeat, respiration, and digestion. Moreover, the ANS regulates the body’s response to stress, inflammation, and pain. However, pathological conditions, such as chronic inflammation and chronic stress are associated with an altered autonomic function, mostly represented by increased SNS activity. Recent in vitro studies demonstrated that the ANS influences joint homeostasis and therefore, might play a crucial role in OA. However, no study has systematically elucidated the autonomic tone in knee OA patients until now. To investigate whether OA patients exhibit an autonomic dysfunction, ANS activity was analzyed in patients in the early stage of OA (early OA), patients in the late stage of OA (late OA), and, as a control, individuals without OA (healthy). Late OA patients were examined before total knee arthroplasty (TKA) and one year after receiving TKA to assess whether possible autonomic alterations are reversed after removal of degenerated and inflamed joint tissues. To comprehensively examine the autonomic status of above-mentioned cohort, sympathetic and parasympathetic characteristics were monitored with a variety of methods. ECGs were recorded to determined specific heart rate variability (HRV) parameters. Moreover, perceived chronic stress and pain levels were assessed using questionnaires. In addition, the concentrations of stress hormones (aldosterone, cortisol, dehydroepiandrosterone sulfate (DHEA-S)), SNS neurotransmitters (epinephrine (E), norepinephrine (NE)) as well as inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP)) were determined in the serum and synovial fluid of the study participants. Since beta blockers systematically inhibit SNS activity, their effect on the age at which late OA patients underwent TKA was evaluated. In general, OA patients displayed a decrease in HRV that was more pronounced in late OA patients than in early OA patients. This alteration indicates a PNS deficiency and/ or SNS overactivity, especially in late OA. In addition, late OA patients demonstrated significantly increased perceived chronic stress levels, significantly higher serum cortisol concentrations, and lower serum DHEA-S levels compared to healthy controls. The serum concentration of aldosterone, E, and NE did not vary significantly between healthy controls and OA patients. However, late OA patients demonstrated increased systemic inflammation indicated by significantly elevated serum IL-6 and CRP. Moreover, late OA patients demonstrated significantly increased perceived pain levels. Together, these findings demonstrate that OA patients exhibit an autonomic imbalance with a more pronounced SNS tone, especially in the late stage of the disease. One year after TKA, HRV, perceived pain levels, and serum cortisol concentrations were partly restored in late OA patients, suggesting an improvement of the autonomic function. However, post-surgical values did not reach the levels of healthy controls, indicating an inherent or remaining autonomic imbalance one year post TKA. Female late OA patients receiving beta blockers were significantly older at the time point of TKA compared to those without beta blocker intake. Consequently, beta blockers may be OA protective, especially in women. In summary, the knowledge of an ANS dysfunction in OA enhances the understanding of OA pathogenesis and pathology. It extends the comprehension of OA beyond a whole-joint perspective to its characterization as a whole-body disease, opening new avenues for potential treatment strategies. The protective role of beta blockers in OA patients supports this hypothesis and highlights the ANS as a promising therapeutic target.