# Exosomes: Roles and Therapeutic Potential in Pain

**Authors:** Yuting Wen, Rui Zhang, Jitong Wang, Zhouyun Ma, Changsheng Dong, Ruixiang Li, Jiange Zhang

PMC · DOI: 10.3390/biomedicines14020414 · Biomedicines · 2026-02-11

## TL;DR

This review explores how exosomes, tiny cell messengers, contribute to pain and could lead to new treatments for pain management.

## Contribution

The paper systematically reviews exosome roles in pain and their therapeutic potential, offering insights for future clinical strategies.

## Key findings

- Exosomes play a key role in intercellular communication during pain signaling.
- Exosomal molecular signatures may aid in the early diagnosis and treatment of pain-related diseases.
- Current research highlights both the promise and technical challenges of exosome-based analgesia.

## Abstract

Pain is a signal that the human body is being damaged or attacked by disease. It significantly impacts quality of life and imposes a substantial economic burden. Current analgesic drugs fail to meet clinical application standards due to limited choice, inadequate efficacy, and side effects. Consequently, the development of new treatment strategies for pain relief is essential. Pain signals are conveyed by nociceptors via the central nervous system to the brain, with cell-to-cell communication serving as a crucial step in the sensory nociceptive process. Exosomes are extracellular vesicles involved in intercellular communication, capable of transporting and delivering biological macromolecules. Growing evidence suggests that exosomes contribute significantly to the pathological processes associated with pain-related diseases. Summarizing the characteristics of exosomes and their molecular cargo under various pain conditions, along with identifying specific exosomal signatures, is essential for the early diagnosis and treatment of such diseases. This review systematically elucidates the molecular and cellular mechanisms of exosomes in pain relief and evaluates their potential therapeutic value in pain management. We aim to deepen the understanding of exosome–pain interactions, thereby laying the foundation for developing novel and promising therapeutic strategies. Furthermore, we scrutinize the current status of clinical research on exosome-mediated analgesia and dissect the prevailing technical challenges and future research directions. Our objective is to provide clear scientific guidance and a theoretical basis to facilitate the clinical translation of exosome therapies.

## Full-text entities

- **Genes:** Mir181a-1 (microRNA 181a-1) [NCBI Gene 735252] {aka Mirn181a-1, Mirn213, miR-213, mir-181a-1, mmu-mir-213}, Tnpo1 (transportin 1) [NCBI Gene 238799] {aka D13Ertd688e, IPO2, Kpnb2, MIP, MIP1, TRN}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Hipk3 (homeodomain interacting protein kinase 3) [NCBI Gene 15259] {aka DYRK6, FIST3, PKY, mir-1902}, Oprm1 (opioid receptor, mu 1) [NCBI Gene 18390] {aka M-OR-1, MOP-R, MOR-1, MOR-1O, Oprm, mor}, Tsg101 (tumor susceptibility gene 101) [NCBI Gene 22088] {aka CC2}, Mir204 (microRNA 204) [NCBI Gene 387200] {aka Mirn204, mir-204, mmu-mir-204}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, Jak2 (Janus kinase 2) [NCBI Gene 16452] {aka Fd17}, Mir26b (microRNA 26b) [NCBI Gene 387219] {aka Mirn26b, mir-26b, mmu-mir-26b}, Trpa1 (transient receptor potential cation channel, subfamily A, member 1) [NCBI Gene 277328] {aka Anktm1, TRPA1b}, Ybx1 (Y box protein 1) [NCBI Gene 22608] {aka 1700102N10Rik, EF1A, MSY1, Nsep1, YB-1, dbpB}, Cd9 (CD9 antigen) [NCBI Gene 12527] {aka Tspan29}, PLD2 (phospholipase D2) [NCBI Gene 5338] {aka PLD1C}, Anxa1 (annexin A1) [NCBI Gene 16952] {aka Anx-1, Anx-A1, C430014K04Rik, Lpc-1, Lpc1}, Cacna1e (calcium channel, voltage-dependent, R type, alpha 1E subunit) [NCBI Gene 12290] {aka A430040I15, BII, Cach6, Cacnl1a6, Cav2.3, Cchra1}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, Il1r1 (interleukin 1 receptor, type I) [NCBI Gene 16177] {aka CD121a, CD121b, IL-1R-1, IL-1R-alpha, IL-1R1, IL-1RT-1}, Lrp1 (low density lipoprotein receptor-related protein 1) [NCBI Gene 16971] {aka A2mr, CD91, Lrp, b2b1554Clo}, Gdnf (glial cell line derived neurotrophic factor) [NCBI Gene 14573] {aka ATF}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Mirlet7b (microRNA let7b) [NCBI Gene 387245] {aka Mirnlet7b, let-7b, mmu-let-7b}, Mir34c (microRNA 34c) [NCBI Gene 723932] {aka Mirn34c, mir-34c, mmu-mir-34c}, Traf6 (TNF receptor-associated factor 6) [NCBI Gene 22034] {aka 2310003F17Rik, C630032O20Rik}, Thbs1 (thrombospondin 1) [NCBI Gene 21825] {aka TSP-1, TSP1, Thbs-1, tbsp1}, Enpp2 (ectonucleotide pyrophosphatase/phosphodiesterase 2) [NCBI Gene 18606] {aka ATX, E-NPP 2, Npps2, PD-Ialpha, Pdnp2, lysoPLD}, Cd81 (CD81 antigen) [NCBI Gene 12520] {aka Tapa-1, Tapa1, Tspan28}, Tlr3 (toll-like receptor 3) [NCBI Gene 142980], Hectd1 (HECT domain E3 ubiquitin protein ligase 1) [NCBI Gene 207304] {aka A630086P08Rik, b2b327Clo, opm}, Rsad2 (radical S-adenosyl methionine domain containing 2) [NCBI Gene 58185] {aka 2510004L01Rik, SAND, Vig1, cig5}, Acan (aggrecan) [NCBI Gene 11595] {aka Agc, Agc1, CSPCP, Cspg1, b2b183Clo, cmd}, Tlr8 (toll-like receptor 8) [NCBI Gene 170744], Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Mir134 (microRNA 134) [NCBI Gene 387152] {aka Mirn134, mir-134, mmu-mir-134}, Mir212 (microRNA 212) [NCBI Gene 387208] {aka Mirn212, mir-212, mmu-mir-212}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Mir124a-3 (microRNA 124a-3) [NCBI Gene 723951] {aka Mirn124a-3, mir-124-3, mir-124a-3}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, Cd63 (CD63 antigen) [NCBI Gene 12512] {aka ME491, Tspan30}, Sp1 (trans-acting transcription factor 1) [NCBI Gene 20683] {aka 1110003E12Rik, Sp1-1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Mir215 (microRNA 215) [NCBI Gene 387211] {aka Mirn215, mir-215, mmu-mir-215}, Vegfb (vascular endothelial growth factor B) [NCBI Gene 22340] {aka VEGF-B, Vrf}, Mir183 (microRNA 183) [NCBI Gene 387178] {aka Mirn183, mir-183, mmu-mir-183}, Col10a1 (collagen, type X, alpha 1) [NCBI Gene 12813] {aka Col10, Col10a-1}, Mir23b (microRNA 23b) [NCBI Gene 387217] {aka Mirn23b, mmu-mir-23b}
- **Diseases:** IBD (MESH:D015212), chronic pain (MESH:D059350), breast cancer (MESH:D001943), CIPN (MESH:D009437), trigeminal neuralgia (MESH:D014277), vascular embolism (MESH:D004617), bladder pain (MESH:D018856), cancer pain (MESH:D000072716), destabilization of the medial meniscus (MESH:D000070600), mechanical allodynia (MESH:D006930), osteolytic destruction (MESH:D008105), HCC (MESH:D006528), joint injury (MESH:D000092464), bone metastasis (MESH:D009362), thrombosis (MESH:D013927), RA (MESH:D001172), Arthritis (MESH:D001168), SNI (MESH:D000080902), neuronal hyperactivity (MESH:D001289), colitis (MESH:D003092), chondrocyte hypertrophy (MESH:D006984), gastrointestinal toxicity (MESH:D005767), cardiovascular disease (MESH:D002318), infection (MESH:D007239), toxicity (MESH:D064420), bone remodeling disorders (MESH:D001847), osteolysis (MESH:D010014), cerebrovascular diseases (MESH:D002561), hypoxic (MESH:D002534), musculoskeletal pain (MESH:D059352), knee pain (MESH:D046788), functional disability (MESH:D003291), nerve (MESH:C537568), pulmonary embolism (MESH:D011655), arthritic (MESH:D015535), OA (MESH:D010003), cystitis (MESH:D003556), cardiotoxicity (MESH:D066126), analgesia (MESH:D000699), cartilage degeneration (MESH:D002357), low back pain (MESH:D017116), CRPS (MESH:D020918), acute and chronic pain (MESH:D059787), non-small-cell lung cancer (MESH:D002289), lumbar disk herniation (MESH:D007405), pain disorders (MESH:D013001), prostate cancer (MESH:D011471), Inflammation (MESH:D007249), injury (MESH:D014947), CIBP (MESH:D001859), OA pain (MESH:D010146), peripheral nerve injury (MESH:D059348), Cancer (MESH:D009369), diabetes (MESH:D003920), drug dependence (MESH:D019966), fibrosarcoma (MESH:D005354), neuroinflammation (MESH:D000090862), chronic myeloid leukemia (MESH:D015464)
- **Chemicals:** ION (MESH:D007477), CS (MESH:D002586), pioglitazone (MESH:D000077205), lipid (MESH:D008055), lipopolysaccharide (MESH:D008070), H+ (MESH:D006859), morphine (MESH:D009020), calcium (MESH:D002118), docetaxel (MESH:D000077143), curcumin (MESH:D003474), NCT04849429 (-), proton (MESH:D011522), GAGs (MESH:D006025), doxorubicin (MESH:D004317), S1P (MESH:C060506), glutamate (MESH:D018698), B (MESH:D001895), BOR (MESH:C022871), ceramide (MESH:D002518), LPA (MESH:C032881), paclitaxel (MESH:D017239)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** PC-3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), SCP28 — Homo sapiens (Human), Sickle cell disease, Induced pluripotent stem cell (CVCL_WR00), OSC-20 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_3087), C4-2B — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_4784)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937818/full.md

## References

155 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937818/full.md

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Source: https://tomesphere.com/paper/PMC12937818