NEURAL CORRELATES OF CENTRAL PAIN IN TRIGEMINAL NEURALGIA: A FUNCTIONAL MRI ANALYSIS

Autori

Valtorta Filippo [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy]

Basaia Silvia [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy]

Albano Luigi [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy; and Neurosurgery and Gamma Knife Radiosurgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy]

Pompeo Edoardo [Vita-Salute San Raffaele University, Milan, Italy; and Neurosurgery and Gamma Knife Radiosurgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy]

Sibilla Elisa [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy]

Sarasso Elisabetta [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy; and Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy]

Emedoli Daniele [Department of Rehabilitation and Functional Recovery, IRCCS Ospedale San Raffaele, Milan, Italy]

Mortini Pietro [Vita-Salute San Raffaele University, Milan, Italy; and Neurosurgery and Gamma Knife Radiosurgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy]

Filippi Massimo [Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, and Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy]

Agosta Federica [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy]

Background and aims

Resting-state functional imaging (rs-fMRI) in trigeminal neuralgia (TN) is known to show hyperactivity in sensorimotor and affective‐pain regions with concurrent insular hypoactivity. The goal of this study was to investigate functional connectivity (FC) alterations in TN patients and their modifications after GKRS.

Methods

Forty-one TN patients and 54 healthy controls, age- and sex-matched, underwent a brain MRI protocol, including rs-fMRI on a 3 Tesla scanner. Patients were scanned at baseline (pre-GKRS) and 3 months after GKRS, while controls were scanned only at baseline. After FSL-standard preprocessing, rs-fMRI data set was decomposed into independent components (ICs) using MELODIC (Multivariate Exploratory Linear Optimized Decomposition into Independent Components), with a free estimation of the number of components. To identify differences in rs-FC networks, General Linear Models (GLMs) were applied in FSL, comparing each original network between patients and controls. Analyses were performed between patients and controls at baseline and 3 months post-GKRS, and within TN subgroups, comparing patients with right-side onset (TNR) and left-side onset (TNL).

Results

Before GKRS, patients showed reduced connectivity(p<0.05) in the ventral default mode network (vDMN), affecting areas such as the precuneus and cingulate gyrus. Conversely, patients had increased connectivity(p<0.05) in the posterior salience, sensorimotor, and basal ganglia networks compared to controls, involving regions like the postcentral gyrus, putamen, and amygdala. At 3-month follow-up, the vDMN reduction remained similar to preoperative levels, while additional reductions(p<0.05) were observed in the precuneus and cerebellum networks. Moreover, patients still showed increased connectivity(p<0.05) in the posterior salience network, though less extensive. Longitudinal analysis indicated that basal ganglia, posterior salience, and sensorimotor networks approaching levels similar to controls, while cerebellum connectivity significantly decreased. Considering TN subgroups, TNR largely drove the overall results due to its higher prevalence, but no significant differences in connectivity were found between subgroups, both preoperatively and post-GKRS.

Conclusion

This study identifies significant alterations in FC in TN patients before and after GKRS compared to controls. These changes may reflect neural adaptations associated with chronic pain in TN. The modifications observed 3 months post-GKRS further support the role of pain in shaping FC. However, the specific networks involved and the mechanisms driving these alterations remain unclear. The similarity between TNR and TNL groups suggests a shared underlying mechanism in TN-related connectivity changes. These findings indicate treatment-induced neuroplasticity, but further research is required to assess the long-term effects of GKRS on brain network reorganization.

REFERENCES

[1] Nardoni L, Tullo MG, Giulia DS, Fiorelli M, Caramia F. Structural brain alterations and changes in resting-state functional connectivity in patients with trigeminal neuralgia: A meta-analysis. Neuroimage Clin. 2025 Feb 27;46:103759. doi: 10.1016/j.nicl.2025.103759. Epub ahead of print. PMID: 40086208; PMCID: PMC11954123.

[2] Canu E, Calderaro D, Castelnovo V, Basaia S, Magno MA, Riva N, Magnani G, Caso F, Caroppo P, Prioni S, Villa C, Pain D, Mora G, Tremolizzo L, Appollonio I, Poletti B, Silani V, Filippi M, Agosta F. Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration. Mol Psychiatry. 2022 Nov;27(11):4809-4821. doi: 10.1038/s41380-022-01612-9. Epub 2022 May 20. PMID: 35595978; PMCID: PMC9734056.

Fundings. Italian Ministry of Health (GR-2021-12374601).