119: Capture of analgesic-responsive facial pain of unrestrained mice in a trigeminal neuralgia model

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary orofacial pain, , , , Assessment and Measurement of Pain/Nociception, Artificial Intelligence/Machine Learning, Behavioral studies, , , , ,

Background and Aims: Trigeminal neuralgia (TN) is a devastating neuropathic pain condition that profoundly impacts human well-being, physically and psychologically. Despite an initial response to carbamazepine (CBZ), many patients become refractory to pharmacotherapy and subsequent invasive procedures. Although preclinical trigeminal neuropathic pain models following extracranial chronic constriction injury (CCI) of the trigeminal nerve have been developed, the injury-induced facial hypersensitivity is rarely CBZ responsive, questioning the models’ relevance to TN. Notably, recent reports reveal that facial pain induced by intracranial CCI of the trigeminal nerve is CBZ responsive and thus better mimics the compression observed in classical TN.

Methods: To measure facial mechanical allodynia in an alert rodent, stimulus-evoked withdrawal is commonly assessed in a restrained setting. Conceivably, restrain-triggered stress could lead to unpredictable behaviors that are not necessarily pain associated. Thus we focused specifically on spontaneous and evoked measures of pain of unrestrained mice in a modified CBZ-sensitive FRICT-ION model. By adopting the sheltering tube method, we aimed to reduce the stress that inevitably occurs in restrained animals.

Results: Several commonly used facial pain measures failed to provide adequate resolution for long-term trigeminal neuropathic pain in the unrestrained setting. Here we developed a high-frame rate videography analysis that reliably captured increased chronic spontaneous asymmetric grooming and mechanically evoked-facial rubbing of the face, ipsilateral to the injury. Importantly, the altered behavioral changes are significantly reversed by a non-sedating dose of CBZ. Using DeepLabCut tracking, we further demonstrate that the speed of head movement following facial mechanical stimulation is another CBZ-sensitive behavioral correlate of pain. Importantly, this speed is not responsive to drugs that have failed to manage TN clinically.

Conclusions: Derived from a clinically relevant preclinical model, our findings should greatly facilitate the development of novel approaches to advance the management of TN.

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Presenting Author: Xiaobing Yu
Submitting Author: Xiaobing Yu

Senior Author: Xiaobing Yu

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Ramiro Colon-Vilella: BS - Department of Anesthesia and Perioperative Care, Division of Pain Medicine, University of California, San Francisco
• Darian Mohsenin: BS - Department of Anesthesia and Perioperative Care, Division of Pain Medicine, University of California, San Francisco
• Biafra Ahanonu: PhD - Department of Anatomy, University of California, San Francisco
• Allan Basbaum: PhD - Department of Anatomy, University of California, San Francisco