Influence of Janus Kinase Inhibitors on the Neuronal Activity as a Proof-of-Concept Model for Itch

Wohlrab J, Stintzing D, Schultz L, Jügelt K, and Schroeder OH.

Shin Pharmacology and Physiology, 2021.

Researchers use bioelectronic assays to demonstrate functional effects of JAKi on the neurosensory system

Previous research has shown that Janus kinases play a role in itch related to dermatological conditions such as atopic dermatitis and psoriasis, but the functional effects of different Janus kinase inhibitors (JAKi) in neurophysiological models are not understood. However, research using mouse frontal cortex models shows that the inhibition of neuronal activity increases with JAK1 selectivity and is dependent on concentration.

To examine neural activity related to JAKi with varying inhibitory patterns, scientists used Axion’s Maestro multielectrode (MEA) platform to analyze cultured cells exposed to different concentrations of tofacitinib, baricitinib, and upadacitinib. The results showed that some JAKi have a direct effect on the neurosensory system including changes in network bursting and synchrony. Although these findings demonstrate for the first time that the influence on electrophysiological neuronal activity increases with isotope selectivity related to JAK1, the authors conclude more research is needed to determine the clinical significance.