• fibromyalgia;
  • psychoneuroimmunology;
  • psychophysiology;
  • biopsychosocial model;
  • psychological adaptation;
  • autonomic nervous system;
  • cortisol;
  • hypothalamic–pituitary–adrenal axis;
  • brain;
  • gray matter

The brain and endocrine system are crucial interfaces responding to pathological and psychological processes. This review discusses whether endocrine deviations and structural and functional changes in the brain are a cause or consequence of fibromyalgia. Studies in patients with fibromyalgia virtually uniformly observed subtle alterations in hypothalamic pituitary adrenal functioning, hyporeactive autonomic nervous system responsiveness to stressors, and structural and functional changes in the brain. Our model proposes that predisposing factors, such as genetic vulnerability and trauma, have led to an alteration of the nociceptive system including several neuroendocrine changes. The resulting pain and associated symptoms, such as sleep disturbance, low fitness, fatigue, stress, and distress, are a cause of new neuroendocrine changes. The model predicts that favorable neuroendocrine changes are to be expected after successful pharmacological or non-pharmacological interventions that target pain and associated symptoms.