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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Main Authors: Chi Zhang, Qian Huang, Neil C Ford, Nathachit Limjunyawong, Qing Lin, Fei Yang, Xiang Cui, Ankit Uniyal, Jing Liu, Megha Mahabole, Hua He, Xuewei Wang, Irina Duff, Yiru Wang, Jieru Wan, Guangwu Zhu, Srinivasa N Raja, Hongpeng Jia, Dazhi Yang, Xinzhong Dong, Xu Cao, Scheffer C Tseng, Shaoqiu He, Yun Guan
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-12-01
Series:eLife
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Online Access:https://elifesciences.org/articles/101269
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author Chi Zhang
Qian Huang
Neil C Ford
Nathachit Limjunyawong
Qing Lin
Fei Yang
Xiang Cui
Ankit Uniyal
Jing Liu
Megha Mahabole
Hua He
Xuewei Wang
Irina Duff
Yiru Wang
Jieru Wan
Guangwu Zhu
Srinivasa N Raja
Hongpeng Jia
Dazhi Yang
Xinzhong Dong
Xu Cao
Scheffer C Tseng
Shaoqiu He
Yun Guan
author_facet Chi Zhang
Qian Huang
Neil C Ford
Nathachit Limjunyawong
Qing Lin
Fei Yang
Xiang Cui
Ankit Uniyal
Jing Liu
Megha Mahabole
Hua He
Xuewei Wang
Irina Duff
Yiru Wang
Jieru Wan
Guangwu Zhu
Srinivasa N Raja
Hongpeng Jia
Dazhi Yang
Xinzhong Dong
Xu Cao
Scheffer C Tseng
Shaoqiu He
Yun Guan
author_sort Chi Zhang
collection DOAJ
description 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.
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spelling doaj-art-55e265c0aaeb41ad867c2758618dc1f92025-08-20T02:50:17ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.101269Human birth tissue products as a non-opioid medicine to inhibit post-surgical painChi Zhang0Qian Huang1Neil C Ford2Nathachit Limjunyawong3Qing Lin4Fei Yang5Xiang Cui6Ankit Uniyal7Jing Liu8Megha Mahabole9Hua He10Xuewei Wang11Irina Duff12Yiru Wang13Jieru Wan14Guangwu Zhu15Srinivasa N Raja16Hongpeng Jia17Dazhi Yang18Xinzhong Dong19https://orcid.org/0000-0002-9750-7718Xu Cao20https://orcid.org/0000-0001-8614-6059Scheffer C Tseng21Shaoqiu He22Yun Guan23https://orcid.org/0000-0003-1321-6655Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesThe Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesBioTissue, Inc, Miami, United StatesBioTissue, Inc, Miami, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States; Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Surgery, Johns Hopkins University, School of Medicine, Baltimore, United StatesAcrogenic Technologies Inc, Rockville, United StatesThe Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, United States; Howard Hughes Medical Institute, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, United StatesBioTissue, Inc, Miami, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States; Department of Neurological Surgery, Johns Hopkins University, School of Medicine, Baltimore, United StatesPain 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.https://elifesciences.org/articles/101269painhuman birth tissuessensory neuronsCD44cytoskeleton rearrangement
spellingShingle Chi Zhang
Qian Huang
Neil C Ford
Nathachit Limjunyawong
Qing Lin
Fei Yang
Xiang Cui
Ankit Uniyal
Jing Liu
Megha Mahabole
Hua He
Xuewei Wang
Irina Duff
Yiru Wang
Jieru Wan
Guangwu Zhu
Srinivasa N Raja
Hongpeng Jia
Dazhi Yang
Xinzhong Dong
Xu Cao
Scheffer C Tseng
Shaoqiu He
Yun Guan
Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
eLife
pain
human birth tissues
sensory neurons
CD44
cytoskeleton rearrangement
title Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
title_full Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
title_fullStr Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
title_full_unstemmed Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
title_short Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
title_sort human birth tissue products as a non opioid medicine to inhibit post surgical pain
topic pain
human birth tissues
sensory neurons
CD44
cytoskeleton rearrangement
url https://elifesciences.org/articles/101269
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