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Related Experiment Video

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Demonstration of Cutaneous Allodynia in Association with Chronic Pelvic Pain
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Pathophysiology of Chronic Pain.

Stanley Lyndon1,2,3

  • 1Center for Brain/Mind Medicine.

The Clinical Journal of Pain
|January 30, 2026
PubMed
Summary
This summary is machine-generated.

Chronic pain transforms protective nociception into maladaptive states. This review identifies mechanisms and targets for durable relief, highlighting chronic pain as a systems disease.

Keywords:
biopsychosocial modelchronic painneuroimmune interactionperipheral and central sensitizationprecision medicine

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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.