Pain and itch processing by subpopulations of molecularly diverse spinal and trigeminal projection neurons

A remarkable molecular and functional heterogeneity of the primary sensory neurons and dorsal horn interneurons transmits pain-and or itch-relevant information, but the molecular signature of the projection neurons that convey the messages to the brain is unclear. Here, using retro-TRAP (translating ribosome affinity purification) and RNA sequencing, we reveal extensive molecular diversity of spino-and trigeminoparabrachial projection neurons. Among the many genes identified, we highlight distinct subsets of Cck(+)-, Nptx2(+)-, Nmb(+)-, and Crh(+)-expressing projection neurons. By combining in situ hybridization of retrogradely labeled neurons with Fos-based assays, we also demonstrate significant functional heterogeneity, including both convergence and segregation of pain-and itch-provoking inputs into molecularly diverse subsets of NK1R- and non-NK1R- expressing projection neurons.

Automated summary

Using retro-TRAP and RNA sequencing, researchers have uncovered extensive molecular diversity of spino-and trigeminoparabrachial projection neurons, including distinct subsets of gene expression. Further investigation revealed significant functional heterogeneity in these projection neurons, showing convergence and segregation of pain-and itch-provoking inputs into molecularly diverse subsets of NK1R- and non-NK1R-expressing neurons.