MDFIC2 is a PIEZO channel modulator that can alleviate mechanical allodynia associated with neuropathic pain
Abstract
PIEZO channels are mechanical force sensors involved in various biological processes, including somatosensation. To date, only a few PIEZO-binding partners have been identified, including MyoD-family inhibitor proteins (MDFI and MDFIC). Here, we show that MDFIC2, a third member of the MDFI protein family with an as-yet-unknown function, is expressed in a subset of nociceptive sensory neurons. MDFIC2 modulates both PIEZO1 and PIEZO2 gating properties by slowing their kinetics and shifting mechanical sensitivity to higher forces. Interestingly, Mdfic2 is downregulated in mouse neuropathic pain models in which mechanical allodynia is a hallmark symptom. We found that intrathecal administration of adeno-associated virus vector encoding MDFIC2 cDNA reduces mechanical sensitivity and attenuates mechanical allodynia in the spared nerve injury neuropathic pain model. These findings demonstrate a mechanism for regulating mechanosensation and highlight a potential therapeutic route for treating mechanical allodynia.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (20)
Abdella M. Habib
Department of Basic Medical Sciences, College of Medicine, Qatar University Health, Qatar University
Shengnan Li
Chenjing Zhang
Center for General Practice Medicine, Department of Gastroenterology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College
Meijun Ji
Center for General Practice Medicine, Department of Gastroenterology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College
Nancy Osorio
Aix Marseille University, INSERM 1263, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement 1260, Centre de recherche en CardioVasculaire et Nutrition
Virginie Penalba
Aix Marseille University, INSERM 1263, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement 1260, Centre de recherche en CardioVasculaire et Nutrition
Jesus M. Torres
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Samuel J. Gossage
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Mehdi A. Rezai
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Amy F. Geard
Department of Pharmacology, University College London School of Pharmacy, University College London
Ahad A. Rahim
Department of Pharmacology, University College London School of Pharmacy, University College London
Ahmed M. M. Mahmoud
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Sonia Santana-Varela
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Jun Zhou
Jing Zhao
John N. Wood
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Andrei L. Okorokov
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Xuelong Zhou
Department of Anesthesiology, Woman’s Hospital, Zhejiang University School of Medicine
James J. Cox
Wolfson Institute for Biomedical Research, Division of Medicine, University College London
Bertrand Coste
Aix Marseille University, INSERM 1263, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement 1260, Centre de recherche en CardioVasculaire et Nutrition