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ALPK1 Expressed in IB4-Positive Neurons of Mice Trigeminal Ganglions Promotes MIA-Induced TMJ pain

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Abstract

Pain is one of the main reasons for patients with temporomandibular joint (TMJ) disorders seeking medical care. However, there is no effective treatment yet as its mechanism remains unclear. Herein, we found that the injection of monoiodoacetate (MIA) into mice TMJs can induce typical joint pain as early as 3 days, accompanied by an increased percentage of calcitonin gene-related peptide positive (CGRP+) neurons and isolectin B4 positive (IB4+) in the trigeminal ganglions (TGs). Our previous study has discovered that alpha-kinase 1 (ALPK1) may be involved in joint pain. Here, we detected the expression of ALPK1 in neurons of TGs in wild-type (WT) mice, and it was upregulated after intra-TMJ injection of MIA. Meanwhile, the increased percentage of neurons in TGs expressing ALPK1 and CGRP or ALPK1 and IB4 was also demonstrated by the immunofluorescent double staining. Furthermore, after the MIA injection, ALPK1−/− mice exhibited attenuated pain behavior, as well as a remarkably decreased percentage of IB4+ neurons and an unchanged percentage of CGRP+ neurons, as compared with WT mice. In vitro assay showed that the value of calcium intensity was weakened in Dil+ neurons from ALPK1−/− mice of TMJ pain induced by the MIA injection, in relation to those from WT mice, while it was significantly enhanced with the incubation of recombinant human ALPK1 (rhA). Taken together, these results suggest that ALPK1 promotes mice TMJ pain induced by MIA through upregulation of the sensitization of IB4+ neurons in TGs. This study will provide a new potential therapeutic target for the treatment of TMJ pain.

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Data Availability

The datasets generated during and/or analysed during the current study are available in the [NAME] repository [PERSISTENT LINK TO DATASETS].

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Acknowledgements

The authors acknowledge the support from microscopy facilities at the State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University. This work was financially supported by the Cultivation Project of the National Natural Science Foundation of Guangdong Maternal and Child Health Hospital (No. YN2017G13), National Natural Science Foundation of China 82101042 (H.M. Li), Natural Science Foundation of Hubei Province of China (2021CFB107), and the Fundamental Research Funds for the Central Universities (2042021kf0176).

Funding

The authors acknowledge the support from microscopy facilities at the State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University. This work was financially supported by the cultivation Project of the National Natural Science Foundation of Guangdong Maternal and Child Health Hospital(No. YN2017G13), National Natural Science Foundation of China 82101042 (H.M. Li), Natural Science Foundation of Hubei Province of China (2021CFB107), and the Fundamental Research Funds for the Central Universities (2042021kf0176).

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  1. Taomin Zhu, Huimin Li and Yuxiang Chen contributed equally to this work.

Authors and Affiliations

  1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, Hubei Province, China

    Taomin Zhu, Huimin Li, Xueke Jia, Xiaohan Ma, Xin Liu, Yaping Feng & Jin Ke

  2. Department of Oral and Maxillofacial Trauma and Temporomandibular Joint Surgery, Hubei-MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China

    Taomin Zhu, Huimin Li, Xueke Jia, Xiaohan Ma, Xin Liu, Yaping Feng & Jin Ke

  3. GuangDong Women and Children Hospital, Guangdong, 511400, China

    Yuxiang Chen

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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Taomin Zhu, Huimin Li, and Yuxiang Chen. Design of the study, Interpretation, and analysis of data were performed by Xueke Jia, Xiaohan Ma, Xin Liu, and Yaping Feng. Jin Ke contributed to the preparation and design of this study and made critical revisions to the important intellectual content. The first draft of the manuscript was written by Taomin Zhu and Jin Ke, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jin Ke.

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No human subject was involved in this study. All animal studies were performed in accordance with the National Guidelines for Housing and Care of Laboratory Animals and were approved by the Ethics Committee for Animal Research, School and Hospital of Stomatology, Wuhan University, China (S07921060L).

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Zhu, T., Li, H., Chen, Y. et al. ALPK1 Expressed in IB4-Positive Neurons of Mice Trigeminal Ganglions Promotes MIA-Induced TMJ pain. Mol Neurobiol 60, 6264–6274 (2023). https://doi.org/10.1007/s12035-023-03462-0

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