Northwestern Medicine investigators have discovered that specific calcium channels help regulate sex differences in the functioning of immune cells for neuroinflammation and overall neuropathic pain, according to findings published in Science Advances.

It provides a foundation for us to continue to investigate what role Orai1 plays in microglial reactivity,” said Kaitlyn DeMeulenaere, a student in the Driskill Graduate Program in Life Sciences (DGP) and co-first author of the study.

Using microglial Orai1 knockout mouse models, they found when Orai1 function was blocked or deleted, Orai1-mediated calcium signaling was lost, ultimately reducing the production of inflammatory cytokines.

Using spinal cord electrophysiology techniques, they found that in male microglial Orai1 knockout mice, the potentiation, or an increase in strength, of synaptic transmission that occurs following nerve injury was reduced.

The findings demonstrate that Orai1 channels are key mediators of microglia-induced neuroinflammation and the sexually dimorphic role of microglia in neuropathic pain, underscoring the importance of developing sex-specific targeted therapies in the future.

Here, we investigated the role of Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion of Orai1 in microglia attenuates Ca 2+ signaling and the production of inflammatory cytokines by proalgesic agonists.