ABSTRACT
The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans. Here, we discovered an exception - a form of mechanical pain evoked by hair pulling. Based on observations in a rare group of individuals with PIEZO2 deficiency syndrome, we demonstrated that hair-pull pain is dependent on PIEZO2 transduction. Studies in control participants showed that hair-pull pain triggered a distinct nocifensive response, including a nociceptive reflex. Observations in rare Aß deafferented individuals and nerve conduction block studies in control participants revealed that hair-pull pain perception is dependent on Aß input. Single-unit axonal recordings revealed that a class of cooling-responsive myelinated nociceptors in human skin is selectively tuned to painful hair-pull stimuli. Further, we pharmacologically mapped these nociceptors to a specific transcriptomic class. Finally, using functional imaging in mice, we demonstrated that in a homologous nociceptor, Piezo2 is necessary for high-sensitivity, robust activation by hair-pull stimuli. Together, we have demonstrated that hair-pulling evokes a distinct type of pain with conserved behavioral, neural, and molecular features across humans and mice.
ABSTRACT
In brain tumor surgery it is difficult to distinguish the marginal zone with the naked eye. Fluorescence techniques can help identifying tumor tissue in the zone during resection and biopsy procedures. In this paper a novel system for combined real-time measurements of PpIX-fluorescence, microcirculation and tissue grey-whiteness is presented and experimentally evaluated. The system consists of a fluorescence hardware with a sensitive CCD spectrometer for PpIX peak detection, a laser Doppler system, optical probes, and a LabView software. System evaluation was done on static fluorescing material, human skin, and brain tumor tissue. The static material indicates reproducibility, the skin measurements exemplify simultaneous fluorescence and microcirculation measurement in real-time, and the tumor tissue showed PpIX peaks. These decreased over time, as expected, due to photo bleaching. In addition, the system was prepared for clinical use and thus laser- and electrical safety issues were considered. In summary, a system for multiparameter measurements during neurosurgery was successfully evaluated in an experimental environment. As a next step the system will be applied in clinical brain tumor biopsies and resections.
