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Exercise-Induced Hypoalgesia: Cellular and Molecular Mechanisms Linking Pain Modulation and Stress Regulation-A
Pavle Gajic1, Ivana Kovac1, Graham Lubinsky1,2
1Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA.
Cells
|May 27, 2026
Summary
Exercise-induced hypoalgesia (EIH) shows physical activity can reduce pain sensitivity by engaging complex neural and immune pathways. Individual responses vary, highlighting the need for personalized exercise strategies in pain management.
Area of Science:
- Neuroscience
- Immunology
- Exercise Physiology
Background:
- Exercise-induced hypoalgesia (EIH) demonstrates physical activity's impact on pain and stress systems.
- EIH effects vary significantly, suggesting a complex, multisystem adaptive process.
- Factors influencing EIH include neural, immune, endocrine, metabolic, musculoskeletal, and psychosocial elements.
Purpose of the Study:
- To synthesize evidence linking pain modulation and stress regulation across biological scales during exercise.
- To explore the neural, immune, and endocrine mechanisms underlying EIH.
- To identify the need for personalized exercise strategies in chronic pain management.
Main Methods:
- Narrative review of human experimental, clinical, preclinical, and translational research.
- Synthesis of evidence on exercise's effects on pain modulatory circuits.
- Analysis of neuroimmune, endocrine, and metabolic adaptations to exercise.
Main Results:
- Exercise activates descending pain modulatory circuits and influences neurotransmitter systems (opioid, endocannabinoid, etc.).
- Exercise modulates neuroimmune responses, including microglial activity and cytokine signaling.
- EIH is a multisystem adaptive process influenced by numerous biological and psychosocial factors.
Conclusions:
- Exercise engages interconnected pain and stress regulatory pathways.
- Understanding individual variability in EIH is crucial for effective pain management.
- Biomarker-informed, personalized exercise approaches are needed for chronic pain and functional recovery.
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