Herein, we described the skull base anatomy underlying the FLIT model, demonstrated the tissue injury associated with the FLIT surgery, optimized surgical technique across different species, and characterized behavioral features of this model. Recently, we reported the foramen lacerum impingement of trigeminal nerve root (FLIT) model ( 11). Inspired by previous work, we sought to develop a clinically relevant rodent model of TN to recapitulate its key clinical features. This phenomenon was consistent with commonly reported oral trigger zones in patients with TN. reported that bodies of rats shook when rats were eating, presumably due to triggered dental pain. In both cases, significant mechanical allodynia was observed. used stereotaxic access from the brain and from the infraorbital fissure, respectively, to compress the trigeminal nerve root ( 9, 10). With these unique features, TN is a distinct diagnosis that is different from trigeminal neuropathic pain, which is any neuropathic pain in the trigeminal territory ( 6– 8). TN often presents with highly characteristic paroxysmal pain attacks, facial tics, and well-defined trigger zones ( 3– 5). It is often caused by impingement or demyelination of the trigeminal nerve root, particularly at its entry zone. As such, it has been called “the suicide disease” in mass media ( 1, 2). Trigeminal neuralgia (TN) is one of the most painful conditions in humans. Taken together, our results indicate that FLIT is a clinically relevant rodent model of TN that could facilitate pain research and therapeutics development. 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. Importantly, when compared with a trigeminal neuropathic pain model (infraorbital nerve chronic constriction injury ), 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. The FLIT model recapitulated key clinical features of TN, including lancinating pain–like behavior and dental pain–like behavior. 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. Recently, we found that a foramen in the rodent skull base, the foramen lacerum, provides direct access to the trigeminal nerve root. Trigeminal neuralgia (TN) is a classic neuralgic pain condition with distinct clinical characteristics.
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