What Are Sleeping C-Fiber Nociceptors? Taking a Question from Human Physiology to Experiment

Studies in humans often reveal questions about patho-physiological phenomena which are not easily addressed by basic science. Lab research on the other hand often provides answers that are hard to translate into clinics. In this new workshop format, we will address the following questions arising from studies on human subjects: What are sleeping human nociceptors? Why do classes of C-fibers show a specific response pattern to electrical stimulation? Sleeping nociceptors are linked to neuropathic pain, but cannot ordinarily be activated by any physiological stimulus, and electrical activation using sine waves is not fiber type specific. Thus, their basic (non-sensitized) state in humans is not characterized and the electrical basis for responsiveness to sine waves is unclear. Therefore, targeting these fibers to prevent or treat neuropathic pain remains an unresolved issue. We will frame the question and hear the answers of basic scientists: The electrical responsiveness of pig sensory neurons to sine waves will be compared to the excitability of iPS-cell-derived sensory neurons. Using RNAseq on human sensory neurons, specific subclasses based on transcriptomics are identified. Combining both approaches using PatchSeq will create a synthesis and can take neuronal classification to a level that has not previously been achieved.