# Exosome-mediated signaling in neuropathic pain

> **NIH NIH R01** · DREXEL UNIVERSITY · 2020 · $392,753

## Abstract

Exosome-mediated signaling in neuropathic pain
Chronic neuropathic pain resulting from injury or malfunction of the nervous system is extremely
difficult to treat. Unlike physiological or acute pain, where pain ceases after the damaged nerves or
tissue heal, neuropathic pain can result in allodynia (pain from a non-painful stimulus) and
hyperalgesia (heightened sensitivity to pain). The profound differences between acute and chronic
pain indicate that pain results from the engagement of highly plastic molecules and circuits.
Exosomes are 30-100 nm vesicles that carry mRNAs, miRNAs, proteins, and lipid mediators to
recipient cells via circulation. Cells use these vesicles to communicate with both adjacent and
distant cells. The molecules present on the surface of these vesicles enable them to target
recipient cells. The exosomal contents vary depending on the source and the physiological
conditions of cells releasing them, as well as on disease states that are known to alter exosome
composition. However, not everything that is present in the parent cell is incorporated into the
exosomes, suggesting that this well-regulated process is dynamically altered by signaling cues.
Exosome uptake results in modulation of gene expression in recipient cells and represents a novel
mechanism of cellular communication. There are no studies to date investigating alterations in
exosome composition, function, and signaling mechanisms in a neuropathic pain state. Our
preliminary data characterizing exosomes in serum from a mouse model of neuropathic pain four
weeks after surgery showed a distinct exosomal miRNA and protein signature compared to sham
control. We hypothesize that alterations in exosomal composition following nerve injury render
them pronociceptive and contribute to the maintenance of chronic neuropathic pain. Using in vitro,
ex vivo and in vivo approaches, we will investigate gene expression changes induced by uptake of
exosomes from the serum of nerve injury model compared to sham control mice. Differences in
exosomal uptake by recipient cells, preference for neurons, astrocytes or glia, alterations in
proinflammatory mediators, thermal and mechanical hypersensitivity induced by exosomes and
reversal of hypersensitivity by inhibition of exosome release will be investigated. These studies will
provide insights on novel signaling mechanisms resulting from exosome release under chronic
neuropathic pain and their role in the maintenance of pain. Elucidation of functional properties of
exosomes can be beneficial in developing novel therapeutic intervention strategies to treat chronic
pain.

## Key facts

- **NIH application ID:** 9952435
- **Project number:** 5R01NS102836-04
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Seena Ajit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,753
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952435

## Citation

> US National Institutes of Health, RePORTER application 9952435, Exosome-mediated signaling in neuropathic pain (5R01NS102836-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952435. Licensed CC0.

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