Persistent pain remains a major clinical problem with a high prevalence and paucity of adequate treatment options. Work here will focus on persistent pain circuitry within the spinal dorsal horn, a major site for the integration of somatosensory information and for circuit-based transformations that underlie persistent pain. Mice are an excellent model system for the study of neural circuits because of their general similarity to humans, ease of genetic manipulations and large number of tools available. However, more detailed cellular or molecular differences between mice and humans can hamper the development of effective therapies. The single-cell transcriptome of mouse dorsal horn was recently determined. Here, we will determine the single-cell transcriptome of macaque dorsal horn (Aim 1), which will allow us to identify cellular and molecular elements of the circuitry that are conserved between these two species. Cellular distribution of the populations will also be assessed (Aim 1). To determine their function in mice, we will use a targeted chemogenetic approach, acutely silencing the neurons while testing behavior (Aim 2). Behavior will be complemented by electrophysiological and morphological analyses (Aim 1). From these studies, the dorsal horn circuitry of mice will be determined in a manner that will predict the analogous circuitry in primates. Information about the organization of the primate dorsal horn will also aid in the development of more effective pain therapies. !
The spinal dorsal horn is a major site for mechanisms that mediate persistent pain, however the molecular, cellular and functional organization of this region is still poorly understood. Circuit studies in mice take advantage of a similar general biology, ease of genetics, cost and efficiency, however, species differences may hamper translation of the work into effective therapies. Here we will perform single cell transcriptome analyses of primate and mouse dorsal horn, using the data to identify conserved excitatory populations for functional analyses in mice that will also apply to primate.
