Sensorimotor and Pain Modulation Brain Abnormalities in Trigeminal Neuralgia: A Paroxysmal, Sensory-Triggered Neuropathic Pain

Abstract

Objective: Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity.

Methods: Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants.

Results: TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia (putamen, caudate, nucleus accumbens) compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration.

Conclusions: TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks.

Figure 1. Analyses were restricted to gray matter masks.

CTA and VBM gray matter analyses were restricted to masks. (A–D) Cortical thickness masks for the left (A & B) and right (C & D) hemispheres, including lateral (A & C) and medial (B & D) views. (E–G) VBM masks of subcortical structures in coronal (E), sagittal (F) and axial (G) views.

Figure 2. Cortical thickness abnormalities in trigeminal neuralgia patients.

CTA revealed significant group differences in several cortical brain regions. Red clusters indicate thinner cortex in patients compared to controls (p<0.05, corrected). Prominent findings of cortical thinning in TN are shown in panels A–C, including graphs of mean cortical thickness values ± SEM (in mm): controls (black bars), patients (red bars). Areas of cortical thickening in TN are highlighted in panel D. Thinner cortex in TN was observed in: (A) the bilateral pgACC; graph illustrates thickness for left cluster; (B) the right insular cortex including the dpINS and the ventral aINS, and (C) the bilateral ventral OFC; graph illustrates thickness for right OFC cluster. TN patients had thicker cortex in (D) the bilateral FP and M1, and contralateral (left) S1; graphs illustrate thickness for right FP cluster and the inferior S1 cluster (putative face area). Abbreviations: LH =  left hemisphere; RH =  right hemisphere; R =  right; L =  left; pgACC =  pregenual anterior cingulate cortex; PCC =  posterior cingulate cortex; aINS =  anterior insula; dpINS =  dorsal posterior insula; OFC =  orbitofrontal cortex; FP =  frontal pole; M1 =  primary motor cortex; S1 =  primary somatosensory cortex.

Figure 3. Regions of greater subcortical volume in patients with trigeminal neuralgia.

VBM analysis revealed significant group differences in several subcortical brain regions. Significant results (p<0.05, corrected) are displayed on the MNI152 (2 mm) T1 brain template. Blue clusters indicate greater GM volume in patients compared to controls. Graphs of normalized GM volumes ± SEM are shown to the right of brain images: controls (black bars), patients (red bars). Increased patient GM volume was observed in: (A) the sensory thalamus, including the MD and VPM thalamus bilaterally; (B) the right amygdala; (C) a cluster spanning the right nucleus accumbens, anterior putamen and caudate; (D) the posterior putamen bilaterally; (E) the PAG (green box shows magnified region). Abbreviations: R =  right; L =  left; MD =  medial dorsal nucleus (thalamus); VPM =  ventral posterior medial nucleus (thalamus); NAc =  nucleus accumbens; PAG =  periaqueductal gray.