Abnormal Local Brain Activity Beyond the Pain Matrix in Postherpetic Neuralgia Patients: A Resting-State Functional MRI Study

Background: Postherpetic neuralgia (PHN) patients suffer debilitating chronic pain, hyperalgesia, and allodynia, as well as emotional disorders such as insomnia, anxiety, and depression. The brain structure and functional basis of PHN are still not fully understood. Objectives: To identify the changes of regional brain activity in resting-state PHN patients using regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods. Correlations between spontaneous pain intensity and ReHo or fALFF were analyzed. Study Design: Observational study. Setting: University hospital. Methods: ReHo, fALFF change was analyzed in 19 PHN patients and 19 healthy controls to detect the functional abnormality in the brains of PHN patients. Correlations between ReHo, fALFF, and PHN pain intensity were assessed in the PHN group. Results: PHN patients exhibited significantly abnormal ReHo and fALFF intensity in several brain regions, including the brainstem, thalamus, limbic system, temporal lobe, prefrontal lobe, and cerebellum compared with healthy controls. Correlation analysis showed that most of the ReHo values of the aforementioned brain regions positively correlated with visual analog scale (VAS) values. But much less correlation was found between fALFF and VAS. Limitations: (a) No specific emotional assessment was given for PHN patients before fMRI scans, therefore we cannot exclude whether the emotional disorders exist in these patients. (b) Relatively short pain duration (mean 5.4 months) and small sample size (n = 19) for the PHN group. Conclusions: For PHN patients, the local brain activity abnormality was not restricted to the pain matrix. Besides regions related to pain perception, areas in charge of affective processes, emotional activity, and pain modulation also showed abnormal local brain activity in a resting state, which may suggest complicated supraspinal function and plasticity change in PHN patients. ReHo was more closely correlated with pain intensity of PHN patients than fALFF. This work indicates that besides physical and emotional pain perception, mood disorder and pain modulation could be characteristics of PHN patients. This also supports the potential use of therapeutic interventions not only restricted to pain alleviation, but also those that attempt to ameliorate the cognitive and emotional comorbidities. Key words: Postherpetic neuralgia, resting-state fMRI (rs-fMRI), mood disorder, limbic sy