Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Background/Objectives: Trigeminal neuralgia (TN) is a severe chronic neuropathic facial pain condition. Although TN can be amenable to surgical treatments, ~25% of patients may have recurrence of pain. Understanding the role of the central nervous system (CNS) gray matter and its impact on surgical treatment effect remains unclear but is of increasing interest. Previous machine learning models identified 13 neuroanatomical regional predictors of TN surgical response. The implications of these regions and how they might relate to clinical status and surgical outcome are not clear. Here, we attempt to further understand CNS alterations in TN by investigating how these potential regional predictors of surgical response may change following surgical treatment, and whether this is related to the degree of pain relief achieved. Methods: Retrospective imaging was acquired from 115 surgically naïve TN patients who underwent Gamma Knife Radiosurgery at Toronto Western Hospital. Patients obtained magnetic resonance imaging scans and reported pain intensity scores before and 3–12 months after surgery. Patients were categorized as responders (≥75% pain relief), partial responders (50–74% pain relief), and non-responders (<50% pain relief). Results: Eight regions spanning default mode, visual, limbic, and dorsal attention networks had significant changes in cortical thickness. Responders demonstrated post-operative neuroplasticity in a greater number of regions with higher within-group statistical significance than both partial and non-responders. Thickening of the contralateral fusiform gyrus was correlated with the degree of pain reduction. Conclusions: Our findings identify key regions impacted by chronic neuropathic pain, which may be associated with pain relief in TN.