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Background: Trigeminal neuralgia (TN) is a severe facial pain condition often requiring surgical treatment. Unfortunately, even technically successful surgery fails to achieve durable pain relief in many patients. The purpose of this study was to use resting-state functional magnetic resonance imaging (fMRI) to: (1) compare functional connectivity between limbic and accessory sensory networks in TN patients vs. healthy controls; and (2) determine if pre-operative variability in these networks can distinguish responders and non-responders to surgery for TN.Methods: We prospectively recruited 22 medically refractory classic or idiopathic TN patients undergoing surgical treatment over a 3-year period, and 19 age- and sex-matched healthy control subjects. fMRI was acquired within the month prior to surgery for all TN patients and at any time during the study period for controls. Functional connectivity analysis was restricted to six pain-relevant brain regions selected a priori: anterior cingulate cortex (ACC), posterior cingulate cortex, hippocampus, amygdala, thalamus, and insula. Two comparisons were performed: (1) TN vs. controls; and (2) responders vs. non-responders to surgical treatment for TN. Functional connectivity was assessed with a two-sample t-test, using a statistical significance threshold of p < 0.050 with false discovery rate (FDR) correction for multiple comparisons.Results: Pre-operative functional connectivity was increased in TN patients compared to controls between the right insular cortex and both the left thalamus [t(39) = 3.67, p = 0.0007] and right thalamus [t(39) = 3.22, p = 0.0026]. TN patients who were non-responders to surgery displayed increased functional connectivity between limbic structures, including between the left and right hippocampus [t(18) = 2.85, p = 0.0106], and decreased functional connectivity between the ACC and both the left amygdala [t(18) = 2.94, p = 0.0087] and right hippocampus [t(18) = 3.20, p = 0.0049]. Across all TN patients, duration of illness was negatively correlated with connectivity between the ACC and left amygdala (r2 = 0.34, p = 0.00437) as well as the ACC and right hippocampus (r2 = 0.21, p = 0.0318).Conclusions: TN patients show significant functional connectivity abnormalities in sensory-salience regions. However, variations in the strength of functional connectivity in limbic networks may explain why some TN patients fail to respond adequately to surgery.

Background: Several neuroimaging studies report structural alterations of the trigeminal nerve in trigeminal neuralgia (TN). Less attention has been paid to structural brain changes occurring in TN, even though such changes can influence the development and response to treatment of other headache and chronic pain conditions. The purpose of this study was to apply a novel neuroimaging technique—texture analysis—to identify structural brain differences between classical TN patients and healthy subjects.Methods: We prospectively recruited 14 medically refractory classical TN patients and 20 healthy subjects. 3-Tesla T1-weighted brain MRI scans were acquired in all participants. Three texture features (autocorrelation, contrast, energy) were calculated within four a priori brain regions of interest (anterior cingulate, insula, thalamus, brainstem). Voxel-wise analysis was used to identify clusters of texture difference between TN patients and healthy subjects within regions of interest (p < 0.001, cluster size >20 voxels). Median raw texture values within clusters were also compared between groups, and further used to differentiate TN patients from healthy subjects (receiver-operator characteristic curve analysis). Median raw texture values were correlated with pain severity (visual analog scale, 1–100) and illness duration.Results: Several clusters of texture difference were observed between TN patients and healthy subjects: right-sided TN patients showed reduced autocorrelation in the left brainstem, increased contrast in the left brainstem and right anterior insula, and reduced energy in right and left anterior cingulate, right midbrain, and left brainstem. Within-cluster median raw texture values also differed between TN patients and healthy subjects: TN patients could be segregated from healthy subjects using brainstem autocorrelation (p = 0.0040, AUC = 0.84, sensitivity = 89%, specificity = 70%), anterior insula contrast (p = 0.0002, AUC = 0.92, sensitivity = 78%, specificity = 100%), and anterior cingulate energy (p = 0.0004, AUC = 0.92, sensitivity = 78%, specificity = 100%). Additionally, anterior insula contrast and duration of TN were inversely correlated (p = 0.030, Spearman r = −0.73).Conclusions: Texture analysis reveals distinct brain abnormalities in TN, which relate to clinical features such as duration of illness. These findings further implicate structural brain changes in the development and maintenance of TN.