Thanks Ewan!

Project led by trio of @felipedefaria.bsky.social, Gabriela Basile Carballo and @melisa-mc.bsky.social, involving collaborators @liu.se Håkan Olausson and Max Larsson. Exciting research is possible thanks to our funders @kawresearch.bsky.social , @vetenskapsradet.bsky.social, Hjarnfonden. 8/8

Zooming out to understand the structure. Mechano-nociceptive pathways are organized hierarchically: nociceptor subtypes are recruited according to tissue and organ context. Mapping these ensembles gives a framework for decoding peripheral representations of pain across the body. 7/8

Surprisingly, expression analysis indicated that subset of Adm+ neurons expressing Uts2b+ were activated only by bladder distension. Can nociceptors be indeed organ-selective? We used a Uts2b:Cre line to confirm that projections of Uts2b+ nociceptors are confined to the bladder. 6/8

Next, we turned to less-studied A-fiber nociceptors. Here we identified Adm+ A-fibers and showed that they were preferentially recruited by visceral stimuli, indicating that fast mechano-nociceptive signaling is also organized by tissue domain. 5/8

Then, we tested the C-fiber nociceptors component. Ensemble composition changed only modestly across an array of skin stimuli. In contrast, representation of cutaneous vs visceral pressure diverged strongly, with Adra2a+ C-fibers dominating response to bladder and colorectal distension. 4/8

To compare nociceptive signaling across submodalities and locations, we focused on lumbosacral dorsal root ganglia, whose neurons innervate both skin and pelvic organs. But first, we built a functional and transcriptomic map of these neurons as a reference. 3/8

This is hard to study because it’s difficult to see which combination of nociceptor classes is activated in vivo during noxious stimulation. We used the calcium integrator CaMPARI to label stimulus-activated neurons, allowing us to profile nociceptive ensembles with single-cell RNA-seq. 2/8

Not a season unfortunately! Next time surstromming is on us.

Thank you for visitng, great experience.

Congratulations, amazing.

Thanks Ted! Exciting and fun work.