Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation

Abstract

Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to facilitate treatment, prevent chronic disability, and improve quality of life.

Figure.

Proposed role of stress-related hypothalamic-pituitary-adrenal (HPA) axis activation in the transition from acute to chronic pain. Acute stress response: pain or non–pain-related stressor activates a normal physiologic stress response (short-term sympathetic release of epinepherine and norepinepherine [E/NE] followed by secretion of the anti-inflammatory hormone, cortisol). An adaptive coping response permits the return to normal levels of E/NE, cortisol, and inflammation; a maladaptive response causes excessive or prolonged cortisol secretion and creates a fear-based memory of the stressful stimulus that is sensitized and readily reactivated by future stressors. Chronic stress response: prolonged cortisol secretion (due to maladaptive coping response to acute stress) results in cortisol dysfunction. Cortisol dysfunction results in unmodulated inflammation following reactivation of the stress response, which may contribute to a cycle of inflammation, depression, and pain; pain is a stressor that may reactivate a proinflammatory stress response, now unmodulated due to cortisol dysfunction.