PainRelief.com Interview with:
Xinyue Liu, Ph.D.
Department of Chemical Engineering and Materials Science
Michigan State University
Siyuan Rao, Ph.D.
Biomedical Engineering Department
Binghamton University, SUNY
PainRelief.com: What is the background for this study?
Response: The background lies in the field of optogenetics and its application to the study and modulation of pain perception. Optogenetics is a powerful tool that allows precise control of neural cell populations using light. It has been widely used in neuroscience to investigate how different cells in the brain and nervous system function and how their activity can be modulated. Specifically, in the context of pain research, optogenetics offers the potential to explore the neural mechanisms underlying pain perception and to develop new therapeutic interventions for pain management.
However, one of the challenges in applying optogenetics to the study of pain and nociceptive circuits is the delivery of light to peripheral nerves that experience mechanical strain during locomotion. Traditional light-delivery devices made from rigid materials, such as glass fibers, are not well-suited for this purpose. They can impede the natural behaviors of animals and may cause tissue damage when used in dynamic conditions.
PainRelief.com: What are the main findings?
Response: To address the challenges in peripheral optogenetics, we aimed to develop an alternative approach using hydrogels, which are soft and stretchable materials with a high water content. Hydrogels have tunable mechanical properties and optical transparency in the visible light range, making them promising candidates for delivering light to peripheral nerves during locomotion. Traditional hydrogels are susceptible to fatigue fracture from repeated deformation during animal movement. In our work, we controlled growth of polymeric nanocrystalline domains to enable the optimized optical and mechanical properties and generate fatigue-resistant hydrogel optical fibers. The hydrogel fibers we developed can withstand locomotion strain across more than 30,000 fiber stretch cycles and allow the optogenetic inhibition of pain hypersensitivity in naturally behaving mice.
As proof-of-concept applications, we implanted these fatigue-resistant hydrogel optical fibers onto the sciatic nerves of mice. These mice were genetically modified to express either rhodopsins or chloride pumps for optogenetic excitation or inhibition of neural activity, respectively. In particular, when we used a chronic inflammatory pain mouse model, we observed that delivering light to the sciatic nerve through these hydrogel fibers mitigated thermal and mechanical hypersensitivity in mice during their natural behaviors.
PainRelief.com: What should readers take away from your report?
Response: Our report demonstrated an innovative approach to delivering light to peripheral nerves during locomotion, which has dual implications: first, the implantation of hydrogel fibers does not affect the normal animal behaviors and activities; second, the animal activities do not affect the effectiveness of light delivery. By engineering hydrogel fibers, the researchers have addressed a significant challenge in optogenetics, allowing for the precise control of neural activity even in dynamic conditions.
PainRelief.com: What recommendations do you have for future research as a result of this study?
Response: For the future research, we are exploring methods for scaling up the synthesis and fabrication of hydrogel optical fibers, which might fit the scope of large animals and primates. In addition, due to the multiplexed nature of optical transmission, future research can focus on light delivery with different wavelengths, which independently modulate specific neuron cell populations. Lastly, our findings indicate the possibility of applying the light delivery technique with hydrogel fibers to other mobile organs beyond peripheral nerves, such as the heart and gastrointestinal system, through customized fiber designs.
PainRelief.com: Is there anything else you would like to add? Any disclosures?
Response: We have no disclosures. It is important to clarify that optogenetics, while a powerful and promising research tool, had not yet fully transitioned to widespread clinical use. It was primarily being employed in laboratory and preclinical studies to better understand neural circuits and functions. Clinical translation and the application of optogenetics in human healthcare were still in the early stages, due to the safety and ethical considerations. For now, we use this technology to help understand the nociceptive circuits and help develop new therapies.
Liu, X., Rao, S., Chen, W. et al. Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion. Nat Methods (2023). https://doi.org/10.1038/s41592-023-02020-9
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Last Updated on October 20, 2023 by PainRelief.com