Neuroimaging study and non-invasive brain stimulation for central poststroke pain

Central poststroke pain (CPSP) is one of the most refractory neuropathic pain, and typically pharmacoresistant. In this paper, we summarized the feature of CPSP, and reviewed non-invasive brain stimulation therapies for treating CPSP and neuro-imaging studies to investigate mechanisms of CPSP, including our studies. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive means to stimulate the brain from the outside of the scalp, and can induce a plastic change in brain functions. The motor cortex stimulation by rTMS was reported to improve neuropathic pain in the upper extremity including CPSP. The putative mechanisms of action of the motor cortex stimulation are that the stimulation acts on the pain-related brain regions and networks to relief pain. Several meta-analyses and clinical guidelines have reported that high-frequency rTMS of the primary motor cortex has a transient pain-relieving effect. That effect of rTMS, however, is still modest and therefore more optimal stimulation conditions are required. We reported that deep rTMS using an H-coil could provide more pain relief than conventional focal rTMS using a figure-8 coil, and rTMS with higher frequency and larger number of pulses might be more effective. No meta-analyses have proved a positive long-term effect after multi-session rTMS which was investigated in a few studies. The effect with long-term interventions should be tested in the future studies. Although it is well known that specific lesions can develop CPSP, not only anatomical changes but also a maladaptation of pain-related brain networks might be underlying mechanisms of CPSP. We are studying a detailed location of lesions and brain network changes using multimodal brain MRI. The voxel-based lesion mapping in 121 CPSP patients with three-dimensional T1 weighted images showed lesion maps in the posterior part of the putamen and the lateral posterior ventral part of the thalamus. Detailed localization of the lesion maps suggested the damage of the insular cortex or the thalamic insular pathway which transferred thermal nociception was one of the key structures or brain networks to develop CPSP. The preliminary study of resting-state functional MRI showed changes in the sensorimotor network in patients with CPSP compared to control subjects. Neuroimaging studies could lead a greater understanding of the pathophysiology of CPSP and developing objective indicators for diagnosis and evaluation of CPSP.