Pathophysiology of Chronic Pain

Area of Science:

• Neuroscience
• Immunology
• Genetics
• Psychology

Background:

• Chronic pain affects 20% of the population, persisting due to maladaptive neural, immune, and psychological changes.
• Protective nociception can convert into chronic pain states, necessitating a deeper understanding of underlying mechanisms.

Purpose of the Study:

• To consolidate mechanistic and clinical evidence on the transformation of nociception into chronic pain.
• To identify therapeutic leverage points for achieving durable pain relief.

Main Methods:

• A narrative review following SANRA guidance, searching multiple databases (PubMed, Embase, etc.) and grey literature.
• Inclusion of studies on biological, immunological, genetic, epigenetic, or psychosocial mechanisms and mechanism-targeted interventions.
• Thematic synthesis and methodological quality appraisal of eligible studies.

Main Results:

• Chronic pain involves a multistage cascade: peripheral, spinal, and supraspinal sensitization.
• Neuro-immune dialogue, microbiome dysbiosis, sex differences, and epigenetics amplify pain.
• Emerging therapies target ion channels, glial activation, cytokines, and the microbiome for precision pain management.

Conclusions:

• Chronic pain is a systems disease requiring integrated, mechanism-based, and person-centered care.
• Understanding the biological scaffold explains treatment failures and guides research for disease-modifying analgesics.
• Future research should focus on equitable delivery models and precision approaches for chronic pain management.