Spinal cord injury (SCI) has a multi-faceted effect on the afflicted individual’s life. One of the most debilitating phenomena to occur in SCI is Central neuropathic pain (CNP). This disorder emerges in about half of the injured individuals and consists of chronic sensory alterations, including spontaneous bouts of burning/ prickling, electric like pain, heightened sensitivity to painful stimuli and a painful experience of normally non-aversive stimuli. CNP has high comorbidity with psychiatric disorders such as depression and PTSD. There are currently neither sufficient treatment options for this population, nor understanding of the underlying mechanism of CNP or why some individuals develop it while others do not.

Neuroimaging studies of CNP in SCI have been scarce, mostly focusing on structural aspects and a few functional connectivity studies focusing on insula and somatosensory areas. Our research focused on pre-frontal areas as the dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex (mPFC), which are critical to top-down modulation of sensory and affective aspects of pain. Specifically, we aimed to examine whether the functional connectivity between the two areas is altered in individuals with SCI who developed CNP compared to those who did not. We further examined whether altered functional connectivity between these prefrontal regions is associated with psychological symptoms of depression and post-traumatic stress disorder (PTSD).  In addition, we examined whether the PFC connectivity affected the functional connectivity between brainstem pain related nuclei and its relation to CNP intensity.  

We recruited 36 participants with spinal cord injury, 24 with CNP and 12 without. Participants underwent an fMRI scan and filled questionnaires that assessed psychological symptomatology and CNP characteristics. Region of interest resting state functional connectivity analysis among the dlPFC, mPFC, periaqueductal gray and rostral ventromedial medulla was assessed. 

dlPFC-mPFC connectivity was found to be significantly different between the groups. Moreover, individuals with SCI without CNP presented higher percentage of negative connectivity, compared to higher percentage of positive connectivity in the CNP group. The dlPFC-mPFC correlation was associated with symptoms of depression and PTSD across all participants posy-SCI. Finally, the interaction of dlPFC-mPFC connectivity with the PAG-RVM connectivity did not significantly affect pain intensity in individuals with post-SCI CNP.  

To the best of our knowledge, our study is the first to focus on the functional connectivity of the PFC in post-SCI CNP. Furthermore, no prior study has emphasized the opposing role of the two PFC sub-regions including the dlPFC and mPFC in individuals post-SCI with CNP compared to those without. Finally, our results imply involvement of specific brain regions which may serve as possible targets for personalized treatment, by incorporating brain imaging in the acute phase of SCI.