Background & Aims

Pathological pain continues to have a major impact on the society as sufferers, making up between 7–8% of the general population, are affected with disrupted somatosensation and debilitating pain. Most of the research on pain mechanisms is focused on rodent models of pain, however, their utility in predicting the efficacy of analgesic drugs in humans has been limited. The paucity of human models of pain has restrained progress in this space and a platform to study human pain mechanisms is highly desirable.
Induced pluripotent stem cells (iPSC) arise from reprogrammed somatic cells and can be differentiated into several cell types including human sensory and cortical neurons. Human iPSC-derived sensory neurons offer a functional and viable model of nociceptors in culture (Aoi Odawara, 2022) (Christian Schinke, 2021), however, conventional cell culture configuration is limited in capturing salient features of the peripheral pain system.

Methods

We have shown that microfluidic cultures allow precise control and manipulation of the neuronal microenvironment while providing a more physiologically relevant model of pain system (Nickolai Vysokov, 2019). We report here development and characterisation of co-cultures of iPSC-derived sensory and cortical neurons in a microfluidic culture platform. This cell culture model has the potential to recapitulate the salient features of human peripheral pain pathway using sensory and cortical neurons. With the use of microfluidic devices, the axons, the soma, and the synaptic connections can be targeted separately using fluidic isolation.

Results

We demonstrate that the microfluidic co-cultures provide a unique platform to investigate modulation of pain transmission using an in vitro model. Additionally, utilising a co-culture will allow investigating the efficacy of novel analgesics in engaging their targets and modulating pain signalling in a context more relevant to human physiology.

Conclusions

Using specific blockers of ion channels/receptors for instance and optimising iPSC derived sensory neurons in microfluidic cultures can offer the opportunity to develop novel analgesics or investigating pain mechanisms.

References

Aoi Odawara, M. S. (2022). In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array. Toxicological Sciences.
Christian Schinke, V. F. (2021). Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC) -derived sensory neurons. Neurobiology of Disease.
Nickolai Vysokov, S. B. (2019). The role of NaV channels in synaptic transmission after axotomy in a microfluidic culture platform. Scientific Reports.

Presenting Author

Laura Kleckner

Poster Authors

Laura Kleckner

PhD

King's College London

Lead Author

E-mail

Topics

  • Novel Experimental/Analytic Approaches/Tools