Pain Chronicity and Relief: From Molecular Basis to Exercise-Based Rehabilitation

Area of Science:

• Neuroscience
• Molecular Biology
• Pain Research

Background:

• Chronic pain, persisting over three months, is a complex health issue.
• Exercise rehabilitation offers non-pharmacological pain relief, but its mechanisms are unclear.
• Current understanding lacks detailed molecular pathways linking exercise to chronic pain relief.

Purpose of the Study:

• To systematically map molecular pathways of exercise-induced analgesia.
• To correlate these pathways with the pathophysiology of chronic pain.
• To identify gaps in translating mechanistic insights into clinical practice.

Main Methods:

• Systematic review of molecular and cellular mechanisms.
• Analysis of peripheral and central sensitization pathways in chronic pain.
• Mapping exercise-induced adaptations onto pain pathophysiology.

Main Results:

• Chronic pain persistence involves peripheral sensitization (inflammatory mediators) and central sensitization (glial activation, NMDA receptor neuroplasticity).
• Exercise interrupts these pathways via endogenous opioid and serotonergic system activation and anti-inflammatory effects.
• Significant gaps exist in personalized exercise prescription based on mechanistic understanding.

Conclusions:

• Exercise modulates key molecular pathways implicated in chronic pain.
• Further research is needed to optimize exercise prescriptions, considering modalities, sex differences, and comorbidities.
• Translational research is crucial for effective, personalized chronic pain management through exercise.