The perception of painful stimuli begins with detection of noxious stimuli by somatosensory neurons called nociceptors. Itch-inducing compounds, on the other hand, are detected by neurons called pruriceptors. We have recently identified the genes expressed in all somatosensory neuron subtypes, including nociceptors and pruriceptors, throughout development and into adulthood. This analysis revealed six transcriptionally distinct subtypes of nociceptors and two subtypes of pruriceptors, each with strikingly distinct gene expression profiles. Importantly, our findings reveal new candidate therapeutic targets to block nociceptors and pruriceptors. We found that select members of the GPCR superfamily, which account for nearly 1/3 of known drug targets, are expressed in nociceptors and pruriceptors, but not other sensory neuron subtypes. We will to leverage our knowledge of somatosensory neurons and the newly identified GPCRs they express to develop new drugs for treating pain and chronic itch while avoiding undesirable side effects. We will focus on drugs that activate Gi/o-coupled GPCRs expressed in nociceptors and pruriceptors because activation of these GPCR subtypes silence neuronal activity.
Pilot
Principal Investigator
PhD
Edward R. and Anne G. Lefler Professor of Neurobiology, Harvard Medical School
Co-PI
PhD
Research Associate in Neurobiology, Harvard Medical School
PhD
Research Fellow in Neurobiology (INT), Harvard Medical School
US20210356455A1
G-protein-coupled receptors (GPCRs) regulating; somatosensation from single-cell transcriptome atlas