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.
Keywords: CD44; cytoskeleton rearrangement; human birth tissues; medicine; mouse; neuroscience; pain; sensory neurons.
Every year, there are about 300 million major surgeries worldwide. Many people experience pain afterward, with some suffering chronic pain. Painkillers commonly used to manage postsurgical pain can have serious side effects. For example, opioid medications, a mainstay therapy for postsurgical pain, can lead to addiction and accidental overdose deaths. Therefore, non-opioid alternatives to manage postsurgical pain are desperately needed. Substances in human birth tissues may offer a new approach to treating postsurgical pain. Tissue from the umbilical cord and the amniotic membrane are routinely discarded after birth. However, some studies have shown that this tissue can be repurposed as a treatment to promote healing and reduce inflammation in the eye and soft tissues. Studies have also suggested that this tissue may provide pain relief. Zhang, Huang, Ford et al. showed that tissue derived from discarded post-birth tissues could reduce postsurgical pain in an animal model. In the experiments, mice with an incision on their paw were treated with the birth tissues. The treatment reduced pain in the animals without common side effects seen with opioid treatment. The experiments also provided insights into how the tissue helps relieve pain. The tissue inhibits nerve cells that sense pain through a pathway that requires a protein in the cell membrane called CD44. A compound from the amniotic tissue, called HC-HA/PTX3, is the key ingredient to this pain relief and can, on its own, relieve pain. The compound rearranges the protein scaffolding and reduces sodium and calcium ion signals in the nerve cells, making the cells less active. The experiments suggest a new approach to postsurgical pain control. Because these natural compounds from post-birth tissues have multiple effects, they may help provide improved pain control and help reduce postsurgical hyperactivity of nerve cells that can lead to chronic pain. More studies are needed to confirm the therapy would be safe and effective in humans.
© 2024, Zhang, Huang, Ford et al.