Subcortical neuroimaging signature of painful disorders of the trigeminal nerve: a UK Biobank study

Background: Trigeminal neuralgia, classified as a painful disorder of the trigeminal nerve (PDTN), is characterized by brief, electric shock-like or stabbing pain localized mainly to the maxillary and mandibular regions. The severity of these paroxysmal attacks severely impairs quality of life and, in extreme cases, may lead to suicidal ideation. We hypothesized that PDTN shares a common neuroanatomical signature with other chronic pain disorders, while also exhibiting disorder-specific alterations. Methods: High-resolution T1-weighted structural MRI scans from 85 individuals diagnosed with painful disorders of the trigeminal nerve (PDTN) and 49,280 control participants from the UK Biobank were analyzed. A non-parametric permutation test (10,000 iterations) randomly reassigned group labels between 85 PDTN cases and 85 individuals reporting no chronic pain or pain-related conditions to generate a null distribution for statistical inference. A second analysis compared the same PDTN group with 85 matched participants reporting chronic pain (excluding orofacial pain), using five covariates and nearest-neighbor matching (1:1 ratio). Results: Compared to individuals reporting no chronic pain, PDTN patients exhibited significant volumetric reductions in eight amygdala and nineteen thalamic nuclei, as well as eighteen hippocampal subfields. When compared to the chronic pain group, significant differences were restricted to six thalamic nuclei and seven hippocampal subfields. Conclusions: These findings underscore that PDTN is associated with a distinct neuroanatomical signature, particularly involving subcortical structures such as the thalamus and hippocampus.