Modification of the resting-state network involved at different stages of neuropathic pain

Neuropathic pain (NeuP) is shown to be associated with abnormal changes in several specific brain regions. However, the large-scale interactivity of neuronal networks underlying the sensory and emotional abnormalities during NeuP remains unexplored. The present study aimed to explore the alterations in the relevant functional resting-state networks (RSNs) and their intra-networks at the different stages of NeuP based on resting-state functional magnetic resonance imaging (rs-fMRI). A NeuP rat model was established by chronic constriction injury (CCI). Three RSNs were identified to be associated with the NeuP, including the default mode network (DMN), sensorimotor network (SMN), and interoceptive network (IN). The functional connectivity (FC) of the left caudate putamen (CPu) within the DMN and the right piriform cortex within the IN were significantly reduced at the early stage of NeuP, when the maximum allodynia was apparent early, which reflected the suppressed function of the DMN and IN. At 4 weeks post-CCI, when negative emotions were present, the FC of the right insular cortex in the SMN and left visual cortex in the IN were significantly elevated, representing the increased excitability of both SMN and IN. Our study revealed the characteristic functional organization at the network level induced by NeuP and emphasized the role of SMN, DMN, and IN in the pathological mechanisms of NeuP.