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, 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.
Authors
- Shao-Qiu He (ORCID: https://orcid.org/0000-0001-9490-6986)
- Xu Cao (ORCID: https://orcid.org/0000-0001-8614-6059)
- Xiang Cui (ORCID: https://orcid.org/0000-0002-3029-5829)
- Neil C. Ford (ORCID: https://orcid.org/0000-0003-3505-5151)
- Yun Guan (ORCID: https://orcid.org/0000-0003-1321-6655)
- Hua He (ORCID: https://orcid.org/0000-0002-7756-1039)
- Xue-Wei Wang (ORCID: https://orcid.org/0000-0002-1196-6447)
- Ankit Uniyal (ORCID: https://orcid.org/0000-0003-3327-4166)
- Xinzhong Dong (ORCID: https://orcid.org/0000-0002-9750-7718)
- Hongpeng Jia (ORCID: https://orcid.org/0000-0001-9558-5563)
- Megha Mahabole
- Chi Zhang (ORCID: https://orcid.org/0000-0001-7306-2243)
- Srinivasa N. Raja (ORCID: https://orcid.org/0000-0001-7991-7636)
- Nathachit Limjunyawong
- Yiru Wang (ORCID: https://orcid.org/0000-0003-4556-6449)
- Dazhi Yang (ORCID: https://orcid.org/0000-0003-2162-6873)
- Guangwu Zhu
- Fei Yang (ORCID: https://orcid.org/0000-0002-9306-6097)
- Qian Huang (ORCID: https://orcid.org/0000-0001-6039-103X)
- Scheffer C.G. Tseng
- Jing Liu (ORCID: https://orcid.org/0000-0003-0520-1541)
- Irina Duff
- Jieru Wan
- Qing Lin (ORCID: https://orcid.org/0009-0002-0601-8247)
Institutions
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Neurological Surgery (US)
Publication Details
- Journal
- eLife
- Published
- 2024-12-13
- DOI
- https://doi.org/10.7554/elife.101269.3
- Citations
- 2
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.65
Funders
- National Eye Institute
- National Institute of Neurological Disorders and Stroke