Abstract
Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder associated with increased risks of anxiety and depression. Converging evidence suggests that chronic pain pathophysiology involves dysfunctional pain-related and emotion-related networks. However, whether these systems are also among the culprit networks for TN remains unclear. Here, we aimed to assess TN-related anatomical and functional brain anomalies in pain-related and emotion-related networks. We investigated differences in gray matter (GM) volume and the related resting-state functional connectivity (rsFC) between 29 classical TN patients and 34 matched healthy controls. Relationships between brain measurement alterations, clinical pain and emotional states were identified. A longitudinal observation was further conducted to determine whether alterations in the brain could renormalize following pain relief. Reduced GM volumes in the bilateral amygdala, periaqueductal gray (PAG) and right insula were found in TN patients compared with healthy control subjects. Whole-brain rsFC analyses with the four above-mentioned anatomical regions as seeds identified three significantly altered functional circuits, including amygdala-DLPFC, amygdala-mPFC and amygdala-thalamus/putamen circuitry. The amygdala-DLPFC and amygdala-mPFC circuits were associated with clinical pain duration and emotional state ratings, respectively. Further longitudinal analysis found that rsFC strength abnormalities in two fronto-limbic circuits (left amygdala/left DLPFC and right amygdala/right PFC) were resolved after pain relief. Together, structural and functional deficits in pain-related and emotion-related networks were associated with TN patients, as demonstrated by our multimodal results. Pain relief had protective effects on brain functional connectivity within fronto-limbic circuits. Our study provides novel insights into the pathophysiology of TN, which may ultimately facilitate advances in TN intervention.
Highlights
Trigeminal neuralgia (TN), a severe neuropathic pain disorder, is estimated to affect one in 15,000–20,000 people worldwide (Katusic et al, 1991; Mueller et al, 2011), and with an even higher prevalence of trigeminal neuralgia (TN) in expanding demographics, including aging individuals (Wang et al, 2015)
No significant differences in age, gender, years of education or head movement between TN patients and healthy control (HC) were found
Visual examination indicated that both TN patients and HCs exhibited remarkably similar resting-state functional connectivity (rsFC) patterns despite some
Summary
Trigeminal neuralgia (TN), a severe neuropathic pain disorder, is estimated to affect one in 15,000–20,000 people worldwide (Katusic et al, 1991; Mueller et al, 2011), and with an even higher prevalence of TN in expanding demographics, including aging individuals (Wang et al, 2015). It has been documented that chronic pain including TN is maladaptive for the brain (Apkarian et al, 2009, 2011; Baliki et al, 2011). Chronic pain including TN patients is often associated with an increased tendency toward depression and anxiety (Baliki and Apkarian, 2015; Wu et al, 2015). Under this circumstance, a better understanding of the brain changes following chronic TN may provide novel insight into the pathophysiologic mechanisms underpinning TN, which in turn, may facilitate advances in intervention
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