(223) Anatomical Organization and Functional Contributions of NK1R Spinal Projection Neurons in Pain and Itch

Abstract

Dissecting the spinal circuitry of pain and itch has been limited by a lack of genetic tools to label discrete subpopulations of spinal neurons. In particular, markers for spinal projection neurons are lacking, and thus the contributions of spinal projection neurons to somatosensation are largely unknown. Currently the only known marker for spinal projection neurons is neurokinin-1 receptor (NK1R), which captures the majority of spinal projection neurons. While neurotoxic ablation studies have provided evidence demonstrating the importance of NK1R spinal projection neurons to itch and hyperalgesia, interpretation of these studies is limited by ambiguities in the time course, specificity, and extent of neuronal death. Here we describe our recently developed NK1R-CreER mouse line as a tool to dissect the spinal circuitry of somatosensation. Using this novel genetic tool, we visualize the outputs of NK1R spinal projection neurons, manipulate their activity and determine their contribution to pain and itch behaviors, and identify new molecular markers using recently published single cell RNA-sequencing of spinal cord dorsal horn neuron populations. These studies shed light on the anatomical organization and functional contributions of NK1R spinal projection neurons to pain and itch. Supported by T32NS086749 and F32NS110155 to TDS and R01NS096705 to SER.