
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

38826432
10.1101/2024.05.19.594874
preprint
4
Article
Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
Zhang Chi
Huang Qian
Ford Neil C.
Limjunyawong Nathachit
Lin Qing
Yang Fei
Cui Xiang
Uniyal Ankit
Liu Jing
Mahabole Megha
He Hua
Wang Xue-Wei
Duff Irina
Wang Yiru
Wan Jieru
Zhu Guangwu
Raja Srinivasa N
Jia Hongpeng
Yang Dazhi
Dong Xinzhong
Cao Xu
Tseng Scheffer C.
He Shao-Qiu
Guan Yun
19 9 2024
2024.05.19.594874https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.05.19.594874
nihpp-2024.05.19.594874.pdf
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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