Biomarkers and Breakdowns: Neuroinflammatory Drivers Linking Sleep Disorders and Chronic Pain

Chronic pain and sleep disturbances are frequently associated and profoundly affect the quality of life, creating intertwined physical, emotional, and social challenges. This narrative review synthesizes current evidence on the molecular mechanisms and pharmacological influences underlying this bidirectional relationship. Elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), neurodegenerative markers (tau, β-amyloid 42), metabolic hormones, and fasting glucose have been consistently associated with both objective and subjective sleep impairments in chronic pain conditions. Pharmacological agents such as melatonin and opioids exhibit heterogeneous effects on neurophysiological pathways, reflecting differences in mechanisms of action and their modulation of biological processes. Rather than offering therapeutic recommendations, this review aims to clarify how these mediators and drugs shape the complex interplay between pain and sleep. Overall, the evidence suggests that persistent dysregulation of inflammatory, neurodegenerative, and metabolic pathways may drive the reciprocal and detrimental interaction between chronic pain and sleep disturbances, highlighting opportunities for targeted research and integrated clinical strategies.