ABSTRACT
Background and Purpose
Small fiber neuropathy (SFN) is a neuropathic disorder that is associated with chronic pain. While most SFN cases are idiopathic, SFN can also have hereditary causes. For example, rare SCN9A gene mutations can impair the NaV1.7 sodium channel, which leads to dorsal root ganglion neuron hyperexcitability, causing SFN. Although chronic pain may induce cerebral changes, the specific structural brain alterations in SCN9A-associated SFN (SFN-SCN9A) remain insufficiently characterized. Therefore, potential alterations in the structural brain network of idiopathic SFN and SFN-SCN9A were explored.
Methods
Ten SFN-SCN9A patients, 20 idiopathic SFN patients, and 20 controls were included. All participants underwent 3-Tesla diffusion MRI (66 gradient directions, b-value = 1200 s/mm2), and the brain network was quantified using nodal importance, which describes the influence of a group of regions on the whole network.
Results
The nodal importance of pain-associated regions (postcentral gyrus, insular cortex, anterior cingulate cortex, and thalamus) was increased in SFN-SCN9A patients compared to controls (β = 0.43, p = 0.02) and idiopathic SFN patients (β = 0.43, p = 0.02). Moreover, higher self-reported pain was associated with higher nodal importance of pain-associated regions in the SFN-SCN9A group (r = 0.67, p = 0.03), while this effect was not observed in the idiopathic SFN patients (r = −0.22, p = 0.34). As self-reported pain did not differ between the SFN groups, it is likely specific to the SCN9A-mutation and not to differences in pain intensity.
Conclusion
Combined, these results suggest the potential involvement of a distinct structural pathway related to pain processing in SFN-SCN9A.
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This post is Copyright: Gerhard S. Drenthen,
Dennis Kool,
Amir Far,
Jaymin Upadhyay,
David E. J. Linden,
Raquel van Gool,
Celine P. Goijen,
Ingemar S. J. Merkies,
Walter H. Backes,
Catharina G. Faber,
Jacobus F. A. Jansen,
Janneke G. J. Hoeijmakers | November 11, 2025
Wiley: Journal of Neuroimaging: Table of Contents