Peripheral signaling pathways contributing to non-histaminergic itch in humans

BACKGROUND: Chronic itch (chronic pruritus) is a major therapeutic challenge that remains poorly understood despite the extensive recent analysis of human pruriceptors. It is unclear how the peripheral nervous system differentiates the signaling of non-histaminergic itch and pain. METHODS: Here we used psychophysical analysis and microneurography (single nerve fiber recordings) in healthy human volunteers to explore the distinct signaling mechanisms of itch, using the pruritogens β-alanine, BAM 8-22 and cowhage extract. RESULTS: The mode of application (injection or focal application using inactivated cowhage spicules) influenced the itch/pain ratio in sensations induced by BAM 8-22 and cowhage but not β-alanine. We found that sensitizing pre-injections of prostaglandin E2 increased the pain component of BAM 8-22 but not the other pruritogens. A-fibers contributed only to itch induced by β-alanine. TRPV1 and TRPA1 were necessary for itch signaling induced by all three pruritogens. In single-fiber recordings, we found that BAM 8-22 and β-alanine injection activated nearly all CM-fibers (to different extents) but not CMi-fibers, whereas cowhage extract injection activated only 56% of CM-fibers but also 25% of CMi-fibers. A "slow bursting discharge pattern" was evoked in 25% of CM-fibers by β-alanine, in 35% by BAM 8-22, but in only 10% by cowhage extract. CONCLUSION: Our results indicate that no labeled line exists for these pruritogens in humans. A combination of different mechanisms, specific for each pruritogen, leads to itching sensations rather than pain. Notably, non-receptor-based mechanisms such as spatial contrast or discharge pattern coding seem to be important processes. These findings will facilitate the discovery of therapeutic targets for chronic pruritus, which are unlikely to be treated effectively by single receptor blockade

Investigation of mass transport processes in a microstructured membrane reactor for the direct synthesis of hydrogen peroxide

Microstructured membrane reactors present a promising approach to master the productivity and safety challenges during the direct synthesis of hydrogen peroxide. However, various mass transport processes occur in this complex system. In order to gain a deeper understanding of these processes, the saturation and desaturation behaviour of the liquid reaction medium with the gaseous reactants is investigated experimentally to examine possible cross-contamination. Moreover, the employed PDMS membrane’s permeances to hydrogen and oxygen are researched at different pressures, by using a variable-pressure/constant-volume setup for the behaviour at ambient pressure and a constant-pressure/variable-volume setup for the behaviour at elevated pressures. A mathematical model in MATLAB is applied to simulate the results. It is shown that a certain desaturation of the gasses through the membrane occurs, and the results are underlined by the modelled ones using a solution-diffusion model in MATLAB. Thus a constant flushing of the gas channels of the reactor is required for safety reasons. Moreover, the measured permeance values indicate that the species transport is mainly limited by the diffusion in the liquid phase and not the membrane resistance