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Foramen lacerum impingement of trigeminal nerve root as a rodent model for trigeminal neuralgia
Weihua Ding, … , Jianren Mao, Shiqian Shen
Weihua Ding, … , Jianren Mao, Shiqian Shen
Published May 9, 2023
Citation Information: JCI Insight. 2023;8(11):e168046. https://doi.org/10.1172/jci.insight.168046.
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Resource and Technical Advance Neuroscience

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

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Abstract

Trigeminal neuralgia (TN) is a classic neuralgic pain condition with distinct clinical characteristics. Modeling TN in rodents is challenging. Recently, we found that a foramen in the rodent skull base, the foramen lacerum, provides direct access to the trigeminal nerve root. Using this access, we developed a foramen lacerum impingement of trigeminal nerve root (FLIT) model and observed distinct pain-like behaviors in rodents, including paroxysmal asymmetric facial grimaces, head tilt when eating, avoidance of solid chow, and lack of wood chewing. 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. On intravital 2-photon calcium imaging, synchronized S1 neural dynamics were present in the FLIT but not the IoN-CCI model, revealing differential implication of cortical activation in different pain models. Taken together, our results indicate that FLIT is a clinically relevant rodent model of TN that could facilitate pain research and therapeutics development.

Authors

Weihua Ding, Liuyue Yang, Qian Chen, Kun Hu, Yan Liu, Eric Bao, Changning Wang, Jianren Mao, Shiqian Shen

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Figure 4

Dental pain–related behavior in the FLIT model.

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Dental pain–related behavior in the FLIT model.
Mice underwent FLIT, IoN...
Mice underwent FLIT, IoN-CCI, and sham surgeries (n = 8 per group, male). Line charts represent mean ± SEM (in color shades). (A) Diagram of incisor overgrowth in the FLIT model. (B) Representative image of incisor overgrowth in the FLIT model. (C) Incisor length. There was significant difference among the 3 groups on 2-way ANOVA test. Post hoc Bonferroni test revealed differences at indicated time points. FLIT versus sham, **P < 0.01, ***P < 0.001; FLIT versus IoN-CCI, $P < 0.05, $$P < 0.01, $$$P < 0.001. (D and E) Dental pain–like behaviors during food chewing. (D) Diagram of head tilt during eating after the FLIT procedure. Left: No head tilt during food chewing before the FLIT surgery. Right: Head tilt while eating after FLIT surgery. (E) Percentage of time eating solid chow was counted in 10 minutes. There was a significant difference among the 3 groups on 2-way ANOVA test. Post hoc Bonferroni’s test revealed differences at indicated time points. FLIT versus sham, ***P < 0.001; FLIT versus IoN-CCI, $$P < 0.01, $$$P < 0.001. (F) Balsa wood weight changes. Mice were singly housed overnight with a balsa wood blocks, and wood weight changes were quantified. There was a significant difference among the 3 groups on 2-way ANOVA test. Post hoc Bonferroni’s test revealed differences at indicated time points. FLIT versus sham, *P < 0.05, **P < 0.01, ***P < 0.001; FLIT versus IoN-CCI, $P < 0.05, $$P < 0.01, $$$P < 0.001. (G) Body weight changes after FLIT procedure. There were significant differences between the 3 groups on 2-way ANOVA test. Post hoc Bonferroni’s test revealed differences at indicated time points. FLIT versus sham, *P < 0.05, **P < 0.01; FLIT versus IoN-CCI, $P < 0.05.

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