PSYCHOLOGICAL VULNERABILITY AND CHRONIC PAIN IN MUSCULOSKELETAL DISORDERS: INTEGRATING NEUROENDOCRINE, IMMUNE, AND BEHAVIORAL MECHANISMS

Abstract

Chronic musculoskeletal pain is a complex phenomenon that involves the influence of biological, psychological and behavioral factors. This review will explore the concept of psychological vulnerability in terms of the mechanisms and pathways by which psychological vulnerability is related to the development, exacerbation and maintenance of pain in musculoskeletal conditions, including neuroendocrine pathways, immune pathways, molecular pathways and behavioural pathways. Depression, anxiety, chronic stress, pain catastrophizing, fear avoidance, hypervigilance, and low resilience may affect pain perception and contribute to functional disability. These all occur in relation to hypothalamic–pituitary adrenal axis dysregulation, abnormal cortisol secretion, sympathetic activation and endogenous pain inhibition. Peripheral and central sensitization are further perpetuated by persistent immune activation, release of pro-inflammatory cytokines and neuroimmune signaling between microglia and astrocytes. Additionally, epigenetic changes and genetic susceptibility could account for variations in pain sensitivity, chronicity, and response to treatment. These biological and psychological processes are reinforced by behavioral mechanisms such as sleep disturbance, physical inactivity, social withdrawal, and maladaptive coping that perpetuate pain and disability. There is supporting evidence for an integrated biopsychosocial approach to the assessment and management of chronic MSK-pain. Applying psychological screening, sleep and activity assessment, molecular biomarkers, physical rehabilitation, stress management and suitable pharmacological treatment could enhance patient stratification and treatment outcomes. The need for future studies in this field is the use of validated multidimensional biomarkers and personalized interventions that target multiple mechanisms involved in this isthmus between vulnerability to pain and persistence in chronic pain.