Association of diurnal cortisol rhythm with chronic pain: Evidence from a prospective cohort study in community-dwelling adults

Despite clinical evidence linking hypothalamic-pituitary-adrenal (HPA) axis dysfunction to chronic pain, epidemiological findings remained mixed. Data from 1246 respondents aged 34-84 at baseline, obtained from the Midlife in the United States (MIDUS) study and its subproject, the National Study of Daily Experiences (NSDE), were used to examine associations between salivary diurnal cortisol rhythms and chronic pain outcomes over a seven-year follow-up period, using mixed-effects logistic regression models adjusted for sociodemographics, lifestyle, and health-related factors. Furthermore, to examine the role of diurnal cortisol rhythms in the development or persistence of chronic pain, the associations were stratified by chronic pain status at baseline. Over a median follow-up of 7.6 years (IQR 6.3-8.3), blunter declines in early post-wake (0.5-4.5 h after waking, OR = 2.16, 95 % CI = 1.41-3.32, P < 0.001) and mid post-wake (4.5-15 h after waking, OR = 1.93, 95 % CI = 1.28-2.90, P < 0.01) cortisol levels were associated with higher odds of developing chronic multisite pain compared to those who remained pain-free at follow-up. In the same subgroup, a blunted early post-wake cortisol decline was associated with higher odds of developing chronic multisite pain, compared to developing chronic non-multisite pain (OR = 2.73, 95 % CI = 1.49-4.99, P < 0.01). No other robust associations were found. Our results suggest that blunted diurnal cortisol declines may play an important role in chronic multisite pain development. PERSPECTIVE: This prospective study found that blunting in diurnal cortisol decline was associated with higher odds of developing chronic multisite pain. The rate of diurnal cortisol decline may provide information for identifying at-risk populations.