Visualization of trigeminal ganglion sensory neuronal signaling regulated by Cdk5.

Minghan Hu, Andrew D Doyle, Kenneth M Yamada, Ashok B Kulkarni

Cell reports 2022 Mar 08

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The mechanisms underlying facial pain are still incompletely understood, posing major therapeutic challenges. Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase involved in pain signaling. However, the regulatory roles of Cdk5 in facial pain signaling and the possibility of therapeutic intervention at the level of mouse trigeminal ganglion primary neurons remain elusive. In this study, we use optimized intravital imaging to directly compare trigeminal neuronal activities after mechanical, thermal, and chemical stimulation. We then test whether facial inflammatory pain in mice could be alleviated by the Cdk5 inhibitor peptide TFP5. We demonstrate regulation of total Ca2+ intensity by Cdk5 activity using transgenic and knockout mouse models. In mice with vibrissal pad inflammation, application of TFP5 specifically decreases total Ca2+ intensity in response to noxious stimuli. It also alleviates inflammation-induced allodynia by inhibiting activation of trigeminal peripheral sensory neurons. Cdk5 inhibitors may provide promising non-opioid candidates for pain treatment. Copyright © 2022. Published by Elsevier Inc.

Citation

Minghan Hu, Andrew D Doyle, Kenneth M Yamada, Ashok B Kulkarni. Visualization of trigeminal ganglion sensory neuronal signaling regulated by Cdk5. Cell reports. 2022 Mar 08;38(10):110458