From Pain Catastrophizing to Hopelessness: Neurobiological Mechanisms, Causes, and Evidence-Based Implications for Pain and Outcomes in Rheumatic Diseases

Pain catastrophizing (PC) and hopelessness are increasingly recognized as central de-terminants of pain severity, disability, and treatment response in individuals with rheumatic and immune-mediated diseases. Traditionally conceptualized as secondary emotional reactions to pain, these cognitive-affective constructs instead represent active mechanisms that shape symptom perception, behavioral responses, and long-term outcomes. In this review, we synthesize evidence across neurobiological, psychological, and clinical domains to elucidate the pathways linking PC and hopelessness to mala-daptive coping, kinesiophobia, and functional decline. Early life stress, trauma, and maladaptive cognitive schemas emerge as upstream vulnerability factors that prime heightened emotional reactivity and reduced prefrontal regulatory control, facilitating amplified pain signaling and fear-based avoidance behaviors. Avoidance and inactivity foster physical deconditioning, fatigue, and higher perceived disability, creating a self-reinforcing cycle that sustains distress and poor quality of life. Moreover, inactivi-ty-related metabolic dysfunction and weight gain may contribute to low-grade in-flammation, particularly in conditions such as psoriatic arthritis, thereby intersecting with biological disease pathways. Importantly, these psychological processes identify a distinct patient subgroup for whom further escalation of immunosuppressive therapy provides limited benefit. Instead, integrated psychological approaches - including cog-nitive-behavioral therapy, acceptance and commitment therapy, and coping-skills training - demonstrate meaningful effects on catastrophizing, agency, and functional recovery. We emphasize the need for routine screening to detect patients with mala-daptive cognitive-emotional profiles and propose a stratified care model prioritizing targeted psychological interventions alongside standard rheumatologic therapy. Future research should refine phenotyping strategies, clarify neuroimmune links, and develop scalable intervention models to break the avoidance cycle and improve patient-centered outcomes.