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Published on: February 28, 2025
Source-Specific Extracellular Vesicle Functions and Engineering Strategies for Chronic Pain Management: A
Chongjie Yao1,2, Jiayang Yu2, Dong Xie3
1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People's Republic of China.
International Journal of Nanomedicine
|May 14, 2026
Summary
Extracellular vesicles (EVs) offer a novel, non-opioid approach to chronic pain. These natural nanoparticles, derived from various cells, can be engineered for targeted delivery, providing effective pain management.
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Pain Research
Background:
- Current chronic pain therapies have limitations, including adverse effects and inadequate long-term pain relief.
- Extracellular vesicles (EVs), natural nanoparticles carrying biomolecules, are emerging as a promising therapeutic alternative.
- Understanding EV function in pain is crucial for developing novel analgesic strategies.
Purpose of the Study:
- To review the therapeutic potential of extracellular vesicles (EVs) in chronic pain management.
- To elucidate the mechanisms by which source-specific EVs modulate different pain types.
- To explore engineering strategies for enhancing EV-based analgesics.
Main Methods:
- Review of literature on EVs from mesenchymal stem cells, neural cells, macrophages, and gut microbiota.
- Assessment of EV activity across nociceptive, neuropathic, and nociplastic pain (ICD-11 classification).
- Analysis of multi-modal regulatory mechanisms including neural signaling, neuroimmunity, neural repair, and metabolic reprogramming.
Main Results:
- Source-specific EVs dynamically regulate diverse pain types through intricate mechanisms.
- EVs influence neural signal transduction, neuroimmune axis, structural neural repair, and metabolic reprogramming.
- Engineering approaches like surface modification and cargo encapsulation can enhance EV targeting and payload delivery.
Conclusions:
- Harnessing innate EV properties, combined with strategic engineering, offers a rational framework for next-generation EV-based analgesics.
- EVs represent a potential non-opioid strategy for precise and effective chronic pain management.
- This review provides insights for developing advanced, targeted therapies for various chronic pain conditions.
