Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
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
Affiliations
Chi Zhang
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Qian Huang
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Neil C Ford
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Nathachit Limjunyawong
The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, United States
Qing Lin
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Fei Yang
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Xiang Cui
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Ankit Uniyal
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Jing Liu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Megha Mahabole
BioTissue, Inc, Miami, United States
Hua He
BioTissue, Inc, Miami, United States
Xuewei Wang
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States; Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, United States
Irina Duff
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Yiru Wang
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Jieru Wan
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Guangwu Zhu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Srinivasa N Raja
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Hongpeng Jia
Department of Surgery, Johns Hopkins University, School of Medicine, Baltimore, United States
Dazhi Yang
Acrogenic Technologies Inc, Rockville, United States
The 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 States
Department 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 States
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.
