Background & Aims
Entrapment neuropathies are painful and disabling diseases caused by chronic nerve compression. Pathophysiology includes small fiber neuropathy, neuroinflammation and hyperexcitability, resulting in nerve dysfunction and neuropathic pain.
After nerve injury, Schwann cells (SC), the myelinating glia of the peripheral nervous system, are reprogrammed into a repair state promoting nerve regeneration, remyelination and immunomodulation. We recently reported that local treatment with SC-derived extracellular vesicles (SC-EV) reduced the sciatic nerve compression-induced hypersensitivity in rats. SC-EV cargo include molecules involved in nerve regeneration, immunomodulation and axonal excitability. We hypothesize that local treatment with SC-EV have beneficial effects on neuropathic pain by modulating the neuroinflammation and the hyperexcitability produced after a sciatic nerve compression.
Methods
We purified SC-EV from primary cultures and studied effects of SC-EV in a rat model of chronic nerve compression (CCI). A single dose of SC-EV was injected in the constricted nerve 4 days after CCI. Mechanical and thermal hypersensitivity were assessed as pain-related behaviors. The infiltration of macrophages and the distribution of type 1 potassium channels (Kv1) were histologically studied.
Results
Unexpectedly, an increase in the nerve macrophage infiltration at the injury site was observed 10 days after the SC-EV administration, suggesting a modulation of the inflammation process by SC-EV. In addition, a subtle change in the Kv1 subtypes Kv 1.2 and Kv1.6 distribution was observed in the compressed nerve after the SC-EV therapy at the same time.
Conclusions
These results suggests that the local treatment with SC-EV after a chronic nerve compression modulates neuroinflammation and potentially, the hyperexcitability of the injured nerve. However, further studies of macrophages polarization and nerve electrophysiology are needed to confirm the relation of these changes with the neuropathic pain alleviation observed after the SC-EV therapy.
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Presenting Author
Dominique Lemaitre
Poster Authors
Topics
- Models: Chronic Pain - Neuropathic