The Role of Cortisol in the Association Between Perceived Stress and Pain: stress and pain: A short report on secondary adrenal insufficiency patients

Background: Given the pain-dampening effect of cortisol, low cortisol levels have often been proposed to mediate the association between perceived stress and pain. However, studying causal effects is difficult given the complex interplay between perceived stress, cortisol release and pain levels in people with an intact hypothalamic-pituitary-adrenal axis. In the current study, we approached this problem by examining the association between perceived stress and pain levels in patients with secondary adrenal insufficiency (SAI) who were successively supplemented by lower and higher doses of hydrocortisone in a double-blinded cross-over design. Methods: Forty-seven patients with SAI (29 males, 18 females; mean [SD] age, 51 [14] years, range 19-73) participated in an RCT. Patients randomly received low doses of hydrocortisone (0.2-0.3 mg/kg body weight/day) during 10 weeks fol-lowed by high doses (0.4-0.6 mg/kg body weight/day) for another 10 weeks, or vice versa. Patients filled out a daily diary on perceived stress (GAD-7) and pain levels (PHQ-15) throughout the RCT. Non-seasonal autoregressive moving average (ARMA) modeling was performed to test associations between daily perceived stress levels and daily pain levels during low and high hydrocortisone dose. Results: Out of 47 study patients, twelve patients showed high enough fluctuations in perceived stress and pain levels (MSSD>0.01) to study their associations during intake of two different hydrocortisone doses. Six patients showed associa-tions between perceived stress and pain during both hydrocortisone doses, one showed this association only under the low dose, and two only under the high dose. Conclusion: This study does not suggest a role for lower cortisol levels in the association between perceived stress and pain