Individual variation in diurnal cortisol in patients with knee osteoarthritis: Clinical correlates

The cortisol awakening response (CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation. To date, however, studies of HPA-axis function among patients with chronic pain are scarce and show equivocal results. The objectives of this study were to investigate the association between CAR and pain-related outcomes and to investigate potential sex differences in patients with knee osteoarthritis (KOA).

In this cross-sectional study, KOA patients (N = 96) completed self-report questionnaires assessing pain and psychosocial factors and underwent Quantitative Sensory Testing (QST) to assess pressure pain threshold (PPT). Additionally, salivary cortisol samples (N = 60) were collected to assess HPA-axis function at 6 time points (awakening, 15- and 30-minute post-awakening, 4 PM, 9 PM and bedtime). The CAR was calculated by examining increases in salivary cortisol from awakening to 30 min post awakening and the total post-awakening cortisol concentration by calculating the lower areas under the curve of cortisol with respect to ground (AUC_G).

Patients with a relatively blunted CAR had significantly higher anxiety levels and lower PPT than patients with relatively normal CAR. Similarly, patients with a relatively reduced AUC_G had significantly higher pain interference and anxiety levels compared to patients with relatively normal AUC_G. PPT was positively correlated with CAR and AUC_G and negatively correlated with pain severity and anxiety_. Men with KOA had significantly lower anxiety, higher PPT and higher CAR and AUC_G than women with KOA. Mediation analysis results revealed a significant indirect effect of PPT on the relationship between sex and AUC_G. CONCLUSIONS: The findings of this study suggest that neuroendocrine factors such as CAR and AUC_G may contribute to individual differences in pain-related outcomes in patients with KOA. Additionally, our results show sex differences in the magnitude of morning HPA activation and pain-related outcomes. Finally, our findings are suggestive of a sex-dependent relationship between post-awakening cortisol concentrations and pain perception. Future research should examine these associations across various pain populations.