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Chronic Pain Causes Peripheral and Central Responses in MIA-Induced TMJOA Rats

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Abstract

Chronic pain is the predominant symptom that drives temporomandibular joint osteoarthritis (TMJOA) patients to seek medical care; however, currently used treatment modalities remain less effective. This study aimed to investigate chronic pain and the peripheral and central responses in monoiodoacetate (MIA)-induced TMJOA rats. First, the appropriate dose of MIA was determined based on pain behavior assessment in rats. Alterations of the condylar structure in TMJOA rats were evaluated by histological staining and micro-computed tomography (micro-CT). Second, the period of TMJOA chronic pain was further explored by assessing the numbers of glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium-binding adaptor molecule 1 (IBA-1)-positive microglia in the trigeminal spinal nucleus (TSN) and performing nonsteroidal anti-inflammatory drug (NSAID) efficacy experiments. Finally, the expression of neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4) in the trigeminal ganglion (TG) and TSN was assessed by immunofluorescence. MIA at 4 mg/kg was considered an appropriate dose. Gradual MIA-induced alterations of the condylar structure were correlated with temporomandibular joint (TMJ) pain. The numbers of GFAP- and IBA-1-positive cells were increased at 2, 3, and 4 weeks after MIA injection. NSAIDs failed to alleviate pain behavior 10 days after MIA injection. CGRP and IB4 levels in the TG and TSN were upregulated at 2 and 4 weeks. These results suggest that TMJOA-related chronic pain emerged 2 weeks after MIA injection. CGRP- and IB4-positive afferents in both the peripheral and central nervous systems may be involved in MIA-induced TMJOA-related chronic pain in rats.

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The data used and analyzed in this article are available upon reasonable request.

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Funding

This study was funded by the National Science Foundation of China (Grant Numbers 81771100 and 81870789).

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Contributions

This study was designed by XL and JK. Data were collected and analyzed by HJ, LX, WL, and MX. HJ drafted the first manuscript. The article was critically revised by XL, JK, and HJ. All authors read and approved the final manuscript.

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Correspondence to Jin Ke or Xing Long.

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The authors declare that they have no conflicts of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The experiments presented in this manuscript comply with the current laws of the country in which they were performed.

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All experiments in this study were conducted in accordance with the Ethics Committee for Animal Research (School and Hospital of Stomatology, Wuhan University, China).

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Jiang, H., Xu, L., Liu, W. et al. Chronic Pain Causes Peripheral and Central Responses in MIA-Induced TMJOA Rats. Cell Mol Neurobiol 42, 1441–1451 (2022). https://doi.org/10.1007/s10571-020-01033-8

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  • DOI: https://doi.org/10.1007/s10571-020-01033-8

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