Role of Inflammatory Cytokines and Endocrine Dysregulation in Pain-Related Cardiovascular and Metabolic Dysfunction:...

Chronic pain is increasingly recognised as a systemic disorder with effects that extend beyond nociception to influence immune, endocrine, cardiovascular, and metabolic systems. Sustained nociceptive activity is associated with low‑grade inflammation and neuroendocrine dysregulation, characterised by elevated pro‑inflammatory cytokines and altered hormonal signalling. These changes are consistently associated with endothelial dysfunction, hypertension, insulin resistance, dyslipidaemia, and increased cardiometabolic risk. This narrative review synthesises evidence from human and preclinical studies published between 2000 and 2025 to examine the immune‑endocrine mechanisms linking chronic pain with cardiovascular and metabolic dysfunction. A structured narrative approach was used, prioritising human studies for clinical relevance and animal studies for mechanistic insight. Evidence suggests that inflammatory cytokines (e.g., interleukin-1β (IL‑1β), interleukin‑6 (IL‑6), tumour necrosis factor-alpha (TNF‑α)) and endocrine pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, insulin signalling, adipokines, and the renin-angiotensin-aldosterone system, interact bidirectionally to perpetuate pain and cardiometabolic disease. However, many findings are associative, and convergent experimental data support plausible causal pathways. Recognising chronic pain as part of a multisystem pathophysiological continuum has important implications for early cardiometabolic screening and integrated clinical management.