Very excited to share our new preprint: "Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use" led by @oliviadavis.bsky.social and Samuel Ferland, a collab between us, Yves De Koninck and Mike Hildebrand labs www.biorxiv.org/content/10.1... - ThreadSky

tedpricethepainguy.bsky.social • 37 days ago

Very excited to share our new preprint: "Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use" led by @oliviadavis.bsky.social and Samuel Ferland, a collab between us, Yves De Koninck and Mike Hildebrand labs https://www.biorxiv.org/content/10.1101/2025.01.19.633733v1

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tedpricethepainguy.bsky.social•37 days ago

KCC2 downregulation in the spinal cord has been a hot topic in the neuropathic pain field since this now classic paper from Yves' lab was published in Nature in 2003 - https://www.nature.com/articles/nature01868

tedpricethepainguy.bsky.social•37 days ago

and then this follow-up from Jeff Coull and the legend himself @simonbeggslab.bsky.social in 2005 linking microglial activation to KCC2 downregulation in neuropathic pain in rodents - https://www.nature.com/articles/nature04223

tedpricethepainguy.bsky.social•37 days ago

There was then an explosion of papers on KCC2 downregulation in the spinal cord in many different models, including this one, again from Yves' lab, showing KCC2 downregulation as a central mechanism of opioid-induced hyperalgesia: https://www.nature.com/articles/nn.3295 led by Francesco Ferrini

tedpricethepainguy.bsky.social•37 days ago

Then there was the discovery of positive modulators of KCC2 function, which took the target from an interesting mechanism, to a potential treatment for many types of pain, and potentially for opioid use disorder: https://www.nature.com/articles/nm.3356

tedpricethepainguy.bsky.social•37 days ago

This year there was a huge announcement from Axonis that they raised a substantial amount of capital to take KCC2 modulators into the clinic for epilepsy and chronic pain, a terrific development for those of us who are passionate about the potential for this target: https://cen.acs.org/business/start-ups/Axonis-Therapeutics-115-million-treat/102/web/2024/10

tedpricethepainguy.bsky.social•37 days ago

But the entire time, the big question has been: can this target be validated in humans? That was the key gap we sought to address in our work. Our conclusion is that there is strong evidence supporting this target for chronic pain and opioid use disorder.

robgereau.bsky.social•37 days ago

beautiful work - congrats Ted, Yves, Mike and teams!

tedpricethepainguy.bsky.social•37 days ago

Thank you Rob!

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