Tseng, S. | bioRxiv Science

bioRxiv2024

Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action

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 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 mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.

neuroscience↗

bioRxiv2021

Collective behavior emerges from genetically controlled simple behavioral motifs in zebrafish

Since Darwin, coordinated movement of animal groups has been believed to be essential to species survival, but it is not understood how changes in the genetic makeup of individuals might alter behavior of the collective. Here we find that even at the early larval stage, zebrafish regulate their proximity and alignment with each other. Two simple visual responses, one that measures relative visual field occupancy and the other global visual motion, suffice to account for the group behavior that emerges. We analyze how mutations in genes known to affect social behavior of humans perturb these simple reflexes in larval zebrafish and thereby affect their collective behaviors. We use model simulations to show that changes in reflexive responses of individual mutant animals predict well the distinctive collective patterns that emerge in a group. Hence group behaviors reflect in part genetically defined primitive sensorimotor "motifs", which are evident even in young larvae.

animal behavior and cognition↗