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Resource and Technical AdvanceIn-Press PreviewNeuroscience Open Access | 10.1172/jci.insight.168046

Foramen lacerum impingement of trigeminal nerve root (FLIT) as a rodent model for trigeminal neuralgia

Weihua Ding,1 Liuyue Yang,1 Qian Chen,2 Kun Hu,3 Yan Liu,4 Eric Bao,5 Changning Wang,6 Jianren Mao,1 and Shiqian Shen1

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Ding, W. in: PubMed | Google Scholar |

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Yang, L. in: PubMed | Google Scholar |

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Chen, Q. in: PubMed | Google Scholar

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Hu, K. in: PubMed | Google Scholar

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Liu, Y. in: PubMed | Google Scholar |

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Bao, E. in: PubMed | Google Scholar

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Wang, C. in: PubMed | Google Scholar

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Mao, J. in: PubMed | Google Scholar

1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

2McGovern Institute for Brain Research, Brain and Cognitive Sciences, MIT, Cambridge, United States of America

3Department of Pathology, Tuft University School of Medicine, Boston, United States of America

4Department of Radiology, Massachusetts General Hospital, Boston, United States of America

5Department of Anesthesia, Brooks School, Bosotn, United States of America

6Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Charlestown, United States of America

Find articles by Shen, S. in: PubMed | Google Scholar

Published May 9, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.168046.
Copyright © 2023, Ding et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 9, 2023 - Version history
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Abstract

Trigeminal neuralgia (TN) is a classical neuralgic pain condition with distinct clinical characteristics. Modeling TN in rodents proves challenging. Recently, we found that a foramen in rodent skull base, the foramen lacerum, provides direct access to the trigeminal nerve root. Using this access, we developed FLIT (Foramen Lacerum Impingement of Trigeminal nerve root) model and observed distinct pain-like behaviors in rodents, including paroxysmal asymmetric facial grimaces, head tilt when eating, avoidance of solid chew, lack of wood chewing, etc. The FLIT model recapitulated key clinical features of TN, including lancinating pain-like behavior, and dental pain-like behavior. Importantly, when compared with a trigeminal neuropathic pain model (infraorbital nerve chronic constriction injury, IoN-CCI), the FLIT model was associated with significantly higher numbers of c-Fos positive cells in the primary somatosensory cortex (S1), unraveling robust cortical activation in the FLIT model. Using intravital two-photon calcium imaging, synchronized S1 neural dynamics were only present in the FLIT but not the IoN-CCI model, revealing differential implication of cortical activation in different pain models. Taken together, FLIT is a clinically relevant rodent model of TN which could facilitate pain research and therapeutics development.

Graphical Abstract
graphical abstract
Supplemental material

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Version history
  • Version 1 (May 9, 2023): In-Press Preview
  • Version 2 (June 8, 2023): Electronic publication

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