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Creating cutting-edge research methods for the next generation of pain treatments
Chronic pain affects up to one in five people worldwide2, and has a massive impact on healthcare systems and economies. However, patients often experience limited relief from available pain treatments,1 and scientists have made limited progress with new treatments in recent years. Many research projects had to be discontinued disappointing patients who have put their hopes on the new approach and losing the resources invested. Due to the especially challenging environment and high attrition rates, many companies and academic institutes are leaving the pain research arena to focus on other areas. But Grünenthal is 100 percent focused on providing innovative, non-opioid pain treatments. We are joining forces with pioneering partners to develop novel methodologies with the power to transform the way pain research is conducted.
Creating better models for early-stage testing of pain medication is one focus area for Grünenthal. The main goal is to humanise the pre-clinical models to ensure translatability of the data into the actual clinical setting. Until now, pre-clinical research was typically based on models conducted with rodents. However, humans and rodents have fundamentally different molecular, cellular and genetic mechanisms when it comes to pain, which means test results from early-stage research could often not be reproduced in the clinical phase.
In close collaboration with pain experts at King’s College London, Grünenthal scientists are developing alternative models for early-stage testing. Together, we are seeking to establish microfluidic culture (MFC) models based on human induced pluripotent stem cells (iPSCs). These advanced models will be specifically tailored for use in pain research. The human cell type is added by iPSCs. Grünenthal has deep expertise in deriving neurons from iPSCs that closely mimic the functionality of human nociceptive neurons – the cells that respond to potentially damaging stimuli by sending signals via the spine to the brain, where the sensation of pain is created. After successful development, this new methodology will enhance our understanding of how medicines affect pain.
“We develop transformative methods for pain R&D to positively impact patients’ lives.”
Our scientists are also joining forces with Uniklinik RWTH Aachen and RWTH Aachen University to advance pain research. The partnership aims to increase our ability to validate potential new treatments in human instead of rodent models by establishing a shared local infrastructure to ethically and reliably source human tissues. This includes Dorsal Root Ganglia (DRGs), which play a key role in transmitting pain signals from the nervous system to the brain. Teams are also comparing human and non-human DRGs to identify the best surrogate species to support pre-clinical research, if no human tissue is available. We are investigating cell-to-cell interactions and co-developing models that can mimic disease mechanisms within a living organism.
These close collaborations with leading scientists in the field of pain research are strong examples of how we are developing innovative R&D methodologies. Successful approaches are directly integrated into drug development activities at Grünenthal. In this way, our pain scientists are striving to improve the process of creating new non-opioid treatments – and providing efficacious pain treatments for patients in need worldwide.
Microfluidic Culture (MFC) Models
MFCs are often called a "lab on a chip" because they represent a device with several compartments that can be equipped with different cell types. Channels that connect the separate compartments allow for the interaction between the different cell types. In this way, MFCs replicate the in-vivo environment of cells more accurately.
Induced Pluripotent Stem Cell (iPSC)
The principle behind iPSCs is ingenious - and highly complex: a body cell is manipulated to revert into a stem cell-like state through a process induced by the scientists. This induced stem cell is pluripotent, which means that regardless of its original function, the induced stem cell can transform into any cell type desired by the scientists - from neurons to heart or liver cells.
1 Pain Alliance Europe. Survey on Chronic Pain. 2017: Diagnosis, Treatment and Impact of Pain. 2017. Available at: https://www.pae-eu.eu/wp-content/uploads/2017/12/PAE-Survey-on-Chronic-Pain-June-2017.pdf (Accessed April 2023)
2 Treede et al Pain 2015 Jun;156(6):1003-1007