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Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
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Sex-Specific White Matter Abnormalities Across the Dynamic Pain Connectome in Neuropathic Pain: A Fixel-Based
Emily P Mills1, Rachael L Bosma1, Anton Rogachov1,2
1Division of Brain, Imaging, and Behaviour, Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
Human Brain Mapping
|January 13, 2025
Summary
Neuropathic pain (NP) is linked to white matter abnormalities in brain networks, particularly in females. These structural changes in the ascending nociceptive system and default mode network may drive functional deficits in chronic pain.
Area of Science:
- Neuroscience
- Neuroimaging
- Pain Research
Background:
- Chronic neuropathic pain (NP) involves functional brain network abnormalities within the dynamic pain connectome (DPC).
- White matter's role in supporting these DPC networks in NP is poorly understood.
- Sex-specific differences in functional abnormalities are noted, but underlying structural variations are unclear.
Purpose of the Study:
- To investigate white matter structural differences in the DPC of individuals with NP compared to healthy controls (HCs).
- To examine sex-specific white matter abnormalities in NP.
- To correlate white matter structure with functional network alterations in NP.
Main Methods:
- Fixel-based analysis of diffusion-weighted imaging data from 80 participants (40 NP, 40 HCs, sex- and age-matched).
- Evaluation of white matter microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section [FDC]) in DPC-related anatomical connections.
- Fixel-wise and connection-specific mean analyses were performed, with a focus on sex-disaggregated data.
Main Results:
- Individuals with NP showed reduced FD and FDC in the corona radiata (sensory thalamus-S1 pathway), primarily driven by females with NP.
- Females with NP exhibited reduced FD in the cingulum (DMN pathway), unlike males with NP.
- Some pathways (anterior insula-temporoparietal junction, sensory thalamus-posterior insula) showed higher FDC in NP individuals, but sex-specific effects were not consistently corroborated.
Conclusions:
- Females with NP present with both microstructural and macrostructural white matter abnormalities within DPC networks, including the ascending nociceptive system and default mode network.
- Aberrant white matter structure is proposed to contribute to or result from functional abnormalities in NP.
- Sex-disaggregated analyses are crucial for identifying specific white matter alterations in clinical conditions like chronic pain.
