The science behind Dolinnov: FXYD2 is needed for neuropathic pain to persist

After showing in 2012 that FXYD2 is present in specific pain-sensing neurons, the team at the Montpellier Institute of Neurosciences asked the next question: what does FXYD2 do there, and does it play a role in chronic pain? The answer was published in Scientific Reports in 2016, with collaborators in Montpellier and at the Max-Delbrück Center in Berlin.

What the study found

Neuropathic pain is caused by damage to the nerves. It often lasts long after the injury, and the treatments available today work only partly. In this study:

• Recording single nerve fibres, the team showed that FXYD2 sets how sensitive some touch- and pain-sensing fibres are to mechanical stimulation.
• Mice lacking FXYD2 developed pain after a nerve injury, but could not keep it over time: the pain hypersensitivity faded.
• In rats with established neuropathic pain, reducing FXYD2 with a short RNA treatment (siRNA) relieved the pain hypersensitivity.
• In human tissue, FXYD2 showed the same restricted pattern in sensory neurons as in rodents.

Why it matters for Dolinnov

This paper moved FXYD2 from an interesting marker to a potential drug target. It showed that FXYD2 is required for neuropathic pain to persist (« chronification »), that lowering it reverses established pain hypersensitivity in animal models, and that the target is conserved in humans. Those three points are the basis of Dolinnov's programme.

Reference

Ventéo S, Laffray S, Wetzel C, et al. Fxyd2 regulates Aδ- and C-fiber mechanosensitivity and is required for the maintenance of neuropathic pain. Scientific Reports. 2016;6:36407. doi:10.1038/srep36407

Previous: finding FXYD2 in pain-sensing neurons (PLoS One, 2012). Next: from target to treatment, an antisense approach for long-lasting pain relief (JCI Insight, 2023).

About Dolinnov

Dolinnov is a preclinical-stage biotech company founded in October 2024 in Montpellier, France, by Grégoire Serra, Stéphanie Ventéo and Jean-Philippe Annereau. It develops Precision Pump Modulators, a new class of non-opioid treatments for chronic pain, starting with an antisense oligonucleotide targeting FXYD2 in pain-sensing neurons.

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