Investigation of neural mechanisms in neuropathic pain and brain plasticity associated with analgesic effect of transcranial direct current stimulation

Abstract

Neuropathic pain is one of the major problems of patients with spinal cord injury (SCI), because it remains refractory to treatment despite a variety of therapeutic approach. Therefore, there is the need for development of new therapeutic approaches and understanding the underlying neural mechanisms of neuropathic pain would be a start. Especially, the structural and functional brain study using multimodal imaging tools will give integrative information of the neural mechanisms of neuropathic pain. Recently, it is suggested that transcranial direct current stimulation (tDCS) can produce lasting changes in corticospinal excitability and can potentially be used for the treatment of neuropathic pain. However, the detailed mechanisms underlying the effects of tDCS are unknown. Sixteen patients suffering from chronic neuropathic pain following SCI (mean age 44.1 ± 8.6 years, 4 females) and 10 healthy controls (39.5 ± 8.6 years, 4 females) underwent [18F]-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET)and magnetic resonance imaging. In study 1, thestructural and functional differences between the patients and healthy controls in brain cortical areas and the structure-function relationships were analyzed. In study 2, the patients received sham or active anodal stimulation of the motor cortex using tDCS for 10 days (20 minutes, 2 mA, twice a day). After the tDCS sessions, [18F]FDG-PET images were acquired from all patients again. The underlying neural mechanisms of tDCS analgesic effect were evaluated by metabolic differences between before and after tDCS. The effect of baseline gray matter volume on brain metabolic changes was also analyzed. In study 1, we found decreases in gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), and hypometabolism in the medial prefrontal cortex in patients compared to healthy controls. Moreover, the changes in one specific imaging modality were correlated with brain regions composed of default mode network of another modality. In study 2, there was a significant decrease in the numeric rating scale scores for pain, from 7.6 ± 0.5 at baseline to 5.9 ± 1.8 after active tDCS (z = –2.410, p = 0.016). We found increased metabolism in the stimulation site and the medulla and decreased metabolism in the left DLPFC and precuneus after active tDCS treatment compared with the changes induced by sham tDCS. Additionally, the change in the DLPFC and precuneus was correlated with tDCS efficacy and baseline gray matter volume in these regions. We found that different imaging modalities commonly identified the possibility of deficits in pain modulation by cognitive and emotional processes in patients with neuropathic pain after SCI and, these abnormal brain changes had correlation with brain regions of default mode network. Moreover the anodal stimulation of the motor cortex using tDCS can modulate these brain regions. Based on these results, we expect that tDCS on the DLPFC could be effective treatment strategy to patients with neuropathic pain following tDCS.