Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action

Zhang, C.; Huang, Q.; Ford, N. C.; Limjunyawong, N.; Lin, Q.; Yang, F.; Cui, X.; Uniyal, A.; Liu, J.; Mahabole, M.; He, H.; Wang, X.; Duff, I.; Wang, Y.; Wan, J.; Zhu, G.; Raja, S. N.; Jia, H.; Yang, D.; Dong, X.; Tseng, S.; He, S.; Guan, Y.

doi:10.1101/2024.05.19.594874

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bioRxiv · 10.1101/2024.05.19.594874

Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action

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Abstract

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.

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Zhang, C., Huang, Q., Ford, N. C., Limjunyawong, N., Lin, Q., Yang, F., Cui, X., Uniyal, A., Liu, J., Mahabole, M., He, H., Wang, X., Duff, I., Wang, Y., Wan, J., Zhu, G., Raja, S. N., Jia, H., Yang, D., Dong, X., Tseng, S., He, S., Guan, Y.. 2024-05-20. Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action. https://doi.org/10.1101/2024.05.19.594874

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