Inhibition of the Ubc9 E2 SUMO-conjugating enzyme–CRMP2 interaction decreases NaV1.7 currents and reverses experimental neuropathic pain :

Abstract The use of infrared laser sources for creation of localized temperature fields has opened new possibilities for basic research and drug discovery. A recently developed technology, Microscale Thermophoresis (MST), uses this temperature field to perform biomolecular interaction studies. Thermophoresis, the motion of molecules in temperature fields, is very sensitive to changes in size, charge, and solvation shell of a molecule and thus suited for bioanalytics. This review focuses on the theoretical background of MST and gives a detailed overview on various applications to demonstrate the broad applicability. Experiments range from the quantification of the affinity of low-molecular-weight binders using fluorescently labeled proteins, to interactions between macromolecules and multi-component complexes like receptor containing liposomes. Information regarding experiment and experimental setup is based on the Monolith NT.115 instrument (NanoTemper Technologies GmbH).

To administer drugs into the spinal subarachnoid space of unanesthetized and intact rats and rabbits, a procedure is described whereby a polyethylene catheter (PE-10) may be inserted through a puncture of the atlanto-occipital membrane and secured to the skull. Calibration experiments carried out with bromophenol blue dye, 3H-naloxone and 14C-urea revealed first, that there was little rostro-caudal diffusion of the injectate along the spinal axis and secondly, that even for compounds such as naloxone which can rapidly permeate neural tissues, the levels which do appear in the brain are small following the spinal subarachnoid administration of the drug. Control injections, administered either acutely or repeatedly over a prolonged period of time, had no detectable effect on the animal's behavior. These observations, as well as the lack of pathology in the spinal cords of rats having such catheters for periods of up to 4 months suggests that the implant is well tolerated.