Correlation between nerve atrophy, brain grey matter volume and pain severity in patients with primary trigeminal neuralgia

Abstract

Background: Recent neuroimaging studies have reported grey matter alterations in primary trigeminal neuralgia patients. However, few studies have focused on quantitative measurements of trigeminal nerves and the interaction between trigeminal nerve volume and brain morphology, particularly grey matter volume. In this study, we investigated the link between trigeminal nerves and grey matter volume changes in primary trigeminal neuralgia patients compared to healthy controls. Moreover, we explored the association of structure of trigeminal nerves and grey matter to collected pain clinical variables.

Methods: Eighty participants (40 patients and 40 controls) were recruited for the study. All participants underwent MRI sessions and clinical pain assessment. Trigeminal nerve volume and whole brain grey matter volume were evaluated using quantitative imaging techniques. Sensory and affective pain rating indices were assessed using the visual analog scale and short-form McGill Pain Questionnaire. Mediation analysis was conducted to investigate the relationship between clinical pain variables and volumetric changes in trigeminal nerves and grey matter.

Results: Decreased trigeminal nerve volume was detected in primary trigeminal neuralgia patients compared to controls. Additionally, reduced grey matter volume was found in several regions associated with pain in primary trigeminal neuralgia subjects, including the insula, secondary somatosensory cortex, hippocampus, dorsal anterior cingulate cortex, precuneus, and several areas of the temporal lobe. Mediation analysis revealed that decreased trigeminal nerve volume drove grey matter volume abnormality of the left insula, and further led to increased pain ratings.

Conclusion: This study showed a predominantly direct effect of trigeminal nerve atrophy on clinical pain variables in primary trigeminal neuralgia patients, providing new insight into the pathophysiology of the disease.

Trial registration: ClinicalTrials.gov ID: NCT02713646.

Keywords: Primary trigeminal neuralgia; pain ratings; trigeminal nerve; voxel-based morphometry.

Conflict of interest statement

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.

Demonstration of neurovascular compression in a TN patient with MRI multiplanar reconstruction technique. (a) Axial 3D-FIESTA and (b) 3D-TOF-MRA sequences exhibit an aberrant superior cerebellar artery (SCA, white arrow) compressing the medial surface of left TGN root (black arrow). (c) Sagittal 3D-FIESTA and (d) 3D-TOF-MRA images demonstrate indentation and deviation of the upper surface of the nerve root by the left SCA. TN: trigeminal neuralgia; TGN: trigeminal nerve; 3D-FIESTA: three-dimensional fast imaging procedure employing steady state acquisition; 3D-TOF-MRA: three-dimensional time-of-flight magnetic resonance angiography.

Figure 2.

Quantitative measurement of the TGN volume in a primary TN patient. Axial 3D-FIESTA images depict the segmentation of bilateral TGN starting from Meckel’s cave to the entry point of the pons ((a)–(d)). In this patient, the right TGN is compressed by a tortuous and enlarged basilar artery, leading to the displacement and atrophy of the nerve, whereas the left TGN remains unaffected.

Figure 3.

Comparisons of ipsilateral and contralateral TGN volume between primary TN patients and controls. Box-and-whisker plot demonstrating that the ipsilateral TGN volume was significantly lower compared to the contralateral TGN volume in primary TN patients and the mean volume of bilateral TGN in healthy controls (p < 0.05). Meanwhile, the ipsilateral TGN of patients with major NVC demonstrated decreased volume compared to those with minor (and without) NVC (p < 0.05). *statistically significant. n.s.: not significant; NVC: neurovascular compression.

Figure 4.

Correlation of ipsilateral TGN volume to different pain indices in primary TN patients. Ipsilateral TGN volume was negatively associated with pain ratings, including (a) the VAS, and (b) the total, (c) sensory, and (d) affective pain rating of SF-MPQ. VAS: visual analog scale; SF-MPQ: the short form of McGill Pain Questionnaire.

Figure 5.

VBM analysis of GMV. VBM analysis revealed significantly decreased GMV clusters in primary TN patients compared to control subjects. In particular, GMV atrophy was observed in the left insula, left S2, right hippocampus, right dACC, bilateral precuneus, and several portions of the temporal lobe (p < 0.05, FDR corrected). Images are shown on the MNI template in neurological convention (x, y, and z values refer to MNI coordinates) with the gradient color bar corresponding to t-values of the clusters. VBM: voxel-based morphometry; MNI: Montreal Neurological Institute; GMV: grey matter volume; S2: secondary somatosensory cortex; dACC: dorsal anterior cingulate cortex; FDR: false discovery rate.

Figure 6.

Association of ipsilateral TGN volume to the GMV of the left insula. The positive correlation was detected between the atrophic ipsilateral TGN and left insula GMV in the primary TN patients (p < 0.01).

Figure 7.

The link between ipsilateral TGN volume, GMV of the left insula, and pain rating index. The mediation analysis showed that the trigeminal nerve morphology, not the left insular GMV, had a predominantly direct effect on the pain severity in primary TN patients.