Purpose: Pain is a physical stressor that can affect hypothalamicpituitary- adrenal (HPA) axis function and cortisol production. Cortisol has important regulatory functions including glucose production, maintenance of the central nervous system, and anti-inflammatory properties that limit the spread of pain. The role of cortisol dysfunction in osteoarthritis (OA) pain mechanisms is unknown. The purpose of this study was to determine 1) if OA-related pain is associated with cortisol levels and diurnal pattern; 2) if the diurnal pattern of cortisol varies with severity of OA pain and 3) if the relationship between OA pain and cortisol is mediated by daily variations in pain, fatigue, stress and negative and positive affect. Methods: This is a secondary data analysis from a community-based study of changes in regional and widespread pain (WSP) among women with chronic pain in Arizona, USA. Eligibility requirements for this analysis included: 1) female; 2) physician-confirmed diagnosis of osteoarthritis of the hip, knee or spine; and 3) onset of symptoms within the last 5 years or a current pain rating of >40 on a 0-100 scale in the past month. Exclusion criteria were: 1) autoimmune or other comorbid disorders causing widespread pain, inflammation, and fatigue (e.g., fibromyalgia, ankylosing spondylitis;) 2) pending litigation regarding the pain condition; and 3) use of daily corticosteroids. Participants (n = 31) completed daily diaries and collected three saliva samples daily (10 AM, 4 PM, and 8 PM) for 7 days. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale assessed severity of OA-related pain. Multilevel regression analyses estimated associations between OA pain and diurnal cortisol levels, controlling for body mass index, medication use, time and day. To assess the diurnal pattern of cortisol, a model with an interaction term of time x WOMAC pain subscale score was fitted as a function of time. Then the association of cortisol levels with OA pain was assessed without the interaction term. A t-test using the median split of the WOMAC pain subscale (=9) was conducted to assess the affect of severity of OA pain. Mediation analyses using the product of the co-efficient approach, examined daily pain intensity, positive and negative affect, fatigue, ratings of stressfulness and enjoyment of daily events as potential mediators of the association between OA pain and cortisol. Results: The mean age was 57 years and average BMI 31kg/m2. Mean WOMAC pain subscale score was 8.8. A non-significant time x WOMAC interaction indicated that WOMAC pain scores did not alter the trajectory of cortisol levels throughout the day [Unstandardized s 0.009 (-0.04, 0.06) p = 0.724]. However, analyses revealed that there was a significant main effect of WOMAC pain subscale scores on cortisol levels [Unstandardized s 0.083 (0.02, 0.15) p =0.009] representing a 0.083 ng/dl increase in cortisol per one unit increase in WOMAC pain score. Women with WOMAC pain scores > 9 had higher cortisol levels than those with scores <9 [mean (sd) 4.20 (0.94) versus 3.83 (0.91) p < 0.001 respectively]. No significant mediated effects were found (Table). Conclusions: In women with OA, disease-related pain is associated with elevated cortisol production, particularly when pain severity is greater. These results are the first to demonstrate that women with OA have altered HPA axis function secondary to disease-related pain. The absence of mediated effects questions the negative affective consequences of pain as a mechanism between pain and ill health. As there are several factors common to OA and cortisol dysfunction including links with obesity, metabolic syndrome and inflammation, future studies should explore alternative variables (e.g., inflammatory cytokines) in the causal pathway between OA pain and cortisol. (Table Presented).
Carlesso, L., Sturgeon, J. A., & Zautra, A. J. (2016). Disease related pain increases cortisol levels in women with OA. Osteoarthritis and Cartilage, 24, S444–S445. https://doi.org/10.1016/j.joca.2016.01.809