Intrinsic brain connectivity differentiates intact endogenous pain modulation in subjects with neuropathic pain after spinal cord injury

Abstract Endogenous pain modulation in humans is frequently investigated with conditioned pain modulation (CPM) and deficient pain inhibition is a proposed mechanism that contributes to neuropathic pain (NP) after spinal cord injury (SCI). Recent studies have combined CPM testing and neuroimaging to reveal neural correlates of CPM efficiency in chronic pain. This study investigated the unexplored differences in CPM efficiency in relation to resting-state functional connectivity (rsFC) between 13 SCI-NP subjects and 13 age- and sex-matched healthy controls (HC). Psychophysical readouts were analyzed to determine CPM efficiency within and between cohorts. To explore group differences of rsFC in relation to CPM efficiency, seed-to-voxel rsFC analyses were performed within pain modulatory regions, e.g., ventrolateral periaqueductal gray (vlPAG) and amygdala. Overall, pain inhibition was not deficient in SCI-NP subjects and was greater in those with more intense NP. In addition, in SCI-NP greater pain inhibition was associated with weaker rsFC between the vlPAG and amygdala with the visual and frontal cortex, respectively, but with stronger rsFC in HC. Taken together, SCI-NP subjects present with intact pain inhibition, but can be differentiated from HC by an inverse relationship between CPM efficiency and intrinsic connectivity of supraspinal regions. Specifically, abnormal neural plasticity could be related to weaker pain modulatory function in SCI-related NP.