Lorivel, T. | bioRxiv Science

bioRxiv2025

Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation

Two-pore domain potassium channels (K2P) regulate neuronal excitability by acting as hyperpolarizing leak channels. Among them, THIK2 remain poorly characterized. Although no study has yet clearly linked them to excitability or pain, their selective expression in nociceptive neurons of the Dorsal Root Ganglia (DRG) suggests a role in nociception and pain regulation. This project investigates THIK2 channels in pain pathophysiology through molecular, electrophysiological, and behavioral approaches. We mapped THIK expression patterns and in THIK2 knock-out mice, we examined DRG neuron excitability and pain sensitivity. Results reveal thermal hypersensitivity under both naive and inflammatory conditions, indicating that THIK2 normally limits neuronal hyperexcitability. These findings position THIK2 as a potential therapeutic target in chronic inflammatory pain, with peripheral inhibition potentially offering analgesia without central opioid side effects.

neuroscience↗

bioRxiv2020

Integration of behavioral and biological variables using penalized regression: an application to the maternal immune activation model of autism

Maternal immune activation (MIA) during pregnancy increases the odds of developing neuropsychiatric disorders such as autism spectrum disorder (ASD) later in life. In pregnant mice, MIA can be induced by injecting the viral mimic polyinosinic:polycytidylic acid (poly(I:C) to pregnant dams resulting in altered fetal neurodevelopmental and behavioral changes in their progeny. Although the murine MIA model has been extensively studied worldwide, the underlying mechanisms have only been partially elucidated. Furthermore, the murine MIA model suffers from lack of reproducibility, at least in part because it is highly influenced by subtle changes in environmental conditions. In human studies, multivariable (MV) statistical analysis is widely used to control for covariates including sex, age, exposure to environmental factors and many others. We reasoned that animal studies in general, and studies on the MIA model in particular, could therefore benefit from MV analyzes to account for complex phenotype interactions and high inter-individual variability. Here, we used a dataset consisting of 26 variables collected on 67 male pups during the course of several independent experiments on the MIA model. We then analyzed this dataset using penalized regression to identify variables associated with in utero exposure to MIA. In addition to confirming the association between some previously described biological variables and MIA, we identified new variables that could play a role in neurodevelopment alterations. Aside from providing new insights into variable interactions in the MIA model, this study highlights the importance of extending the use of MV statistics to animal studies.

neuroscience↗