The glymphatic system in trigeminal neuralgia: Associations with surgical response
The 5th Annual MSC Emerging Science Contest for Early-Career Investigators took place on January 7, 2026. Below is a description of one of the presentations from the contest. (A recording of the event is available here).
Category: Trigeminal pathways
Winner: Abigail Wolfensohn, University of Toronto
Title: The glymphatic system in trigeminal neuralgia: Associations with surgical response
Description: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder that causes severe facial pain. TN is often responsive to neurosurgical interventions, such as Gamma Knife Radiosurgery (GKRS), making it a useful model for exploring the differences between pain and pain-free states. The glymphatic system (GS), a recently identified waste clearance pathway in the brain, has been associated with aging, neuroinflammation, sleep disturbances, and neurodegeneration, yet its role in chronic pain remains understudied. As a result, we assessed GS function in TN using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, a noninvasive magnetic resonance imaging-based biomarker of glymphatic clearance. We hypothesized that TN patients would exhibit reduced glymphatic clearance, indicated by lower DTI-ALPS index compared to healthy controls (HCs), both before and after undergoing GKRS. T1-weighted and diffusion MRI data was collected from 116 surgically naive TN patients and 116 age- and sex- matched HCs. A subset of 95 TN participants undergoing GKRS underwent additional imaging 6 to 12 months postoperatively to evaluate any changes following successful or unsuccessful surgical pain relief.
We found that TN patients exhibited significantly worse DTI-ALPS indices compared to HCs – indicating worse glymphatic clearance – and that this effect remained even after surgery, regardless of whether the patient experienced pain relief. These findings suggest that people living with TN experience persistent glymphatic system disruptions even after receiving treatment, offering novel insight into the relationship between the glymphatic system, trigeminal facial pain and chronic pain conditions, and overall brain health. Furthermore, glymphatic dysfunction could serve as a potential biomarker for chronic neuropathic pain and may open new avenues for therapeutic strategies aimed at supporting brain clearance mechanisms, improving neurological health, and enhancing patient outcomes.