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

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.