Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain

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, attenu...

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Published in:eLife 2024-12, Vol.13
Main Authors: Zhang, Chi, Huang, Qian, Ford, Neil C, Limjunyawong, Nathachit, Lin, Qing, Yang, Fei, Cui, Xiang, Uniyal, Ankit, Liu, Jing, Mahabole, Megha, He, Hua, Wang, Xuewei, Duff, Irina, Wang, Yiru, Wan, Jieru, Zhu, Guangwu, Raja, Srinivasa N, Jia, Hongpeng, Yang, Dazhi, Dong, Xinzhong, Cao, Xu, Tseng, Scheffer C, He, Shaoqiu, Guan, Yun
Format: Article
Language:English
Subjects:
Amnion
Animals
C-Reactive Protein - metabolism
Care and treatment
CD44
cytoskeleton rearrangement
Female
Ganglia, Spinal - drug effects
human birth tissues
Humans
Hyaluronan Receptors - metabolism
Hyaluronic Acid - pharmacology
Liu Jing
Mice
Neurons
Neurons - drug effects
Neurons - physiology
Neurophysiology
Opioids
Pain
Pain, Postoperative
Pain, Postoperative - drug therapy
sensory neurons
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Summary: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 DRG 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 neuronal mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.101269