NGN-PET

An urgent need for pain relief

Neuropathic pain is a chronic condition affecting around 8 % of the population. It can be triggered in various ways, including through surgery, chemotherapy, injury, diabetes, and viral infection. Current treatments are only effective in a minority of patients. Furthermore, treatments address the symptoms, not the underlying causes of the pain, and so are not curative.

One reason for this is that the underlying causes of neuropathic pain are poorly understood. For many years, pain researchers focused almost exclusively on neurons, in the belief that neuron problems were at the root of many patients’ pain. However, more recent research suggested that other cells in the nervous system (such as glial cells) as well as immune cells may also contribute to neuropathic pain. There are many different types of glial cells, and their role in the nervous system includes supporting nerve cells, insulating them, and providing them with nutrients and oxygen.

NGN-PET set out to explore the interactions between neurons and glial cells, and their role in neuropathic pain, in greater detail.

Potential new drug targets identified

Part of the project studied neuropathic pain in two animal models – one that mimics surgery-induced neuropathic pain, and one that mimics chemotherapy-induced neuropathic pain. Crucially, the team confirmed the role of neuron-glial interactions in the generation of a pain response, and identified a number of microglial genes that appear to be involved in the pain response. These genes represent potential drug targets and the pharmaceutical companies in the project are now using this information in their drug development programmes.

The studies also highlighted the role of immune cells in chronic pain – they continued to find large numbers of immune cells in the surgery-induced pain model two and a half months after the initial injury, suggesting that neuro-immune interactions are important.

Pain in a petri dish

Another part of the project focused on developing pain-relevant cells from human induced pluripotent stem cells (hiPSCs). HIPSCs are ordinary cells that have been reprogrammed so that they can potentially become any type of cell in the body, including the cells of the nervous system. Cell cultures developed this way allow scientists to study human diseases in the lab, using human cells.

In NGN-PET, the team developed two types of cells: primary sensory neurons, and resident macrophages (immune cells that play in important role in chronic pain). Developing human sensory neurons from hIPSCs, upscaling their production and freezing them for distribution is extremely difficult, and the standard operating procedure (SOP) that the project developed to do this successfully is a key output of the project.

The project also implemented protocols to create and distribute macrophages and, crucially, created co-cultures including both sensory neurons and macrophages. To these co-cultures, the team added vincristine, a chemotherapy drug that often causes neuropathic pain. The result is a ‘pain in a petri dish’ model that allows researchers to study chemotherapy-induced neuropathic pain in the lab.

A pain drug screening platform

The project assembled the tools it developed into a pain drug screening platform which can be used to screen, identify and evaluate potential drugs to treat neuropathic pain.

Progress on pain relief

The project results are already helping the project partners in their own drug development research. For example, the proteins and genes identified in the animal models are being evaluated as potential targets for new pain relief drugs, and the partners are also using the ‘pain in a dish’ co-cultures in their research.

Furthermore, many of the project outputs are available to the wider scientific community. For example, the freely-accessible NIPPY (‘Neuro-Immune interactions in the Periphery’) website allows scientists to examine neuro-immune interactions relevant to pain.

The tools developed by the project have been incorporated into the research services offered by Axxam, the Italian SME that coordinated NGN-PET. The tools can be accessed via research collaboration agreements or commercial agreements. Thanks to these tools, as well as the expertise, knowledge and contacts acquired during the project, Axxam has acquired a number of new contracts and grants and signed new partnership deals. German SME Life&Brain is also exploring how to incorporate the NGN-PET results into its services. Both SMEs have hired new staff thanks to the increased business generated by their involvement in NGN-PET.

Finally, and looking to the future, NGN-PET confirmed the importance of neuron-glial interactions in neuropathic pain, and this is already reinvigorating research into new, safe, effective pain relief treatments that patients so badly need.