Abstract
Neuropathic pain (NP) is a devastating chronic pain condition affecting roughly 80% of the spinal cord injury (SCI) patient population. Current treatment options are largely ineffective and neurophysiological mechanisms of NP are not well-understood. Recent studies in neuroimaging have suggested that NP patients have differential patterns of functional activity that are dependent upon the neurological condition causing NP. We conducted an exploratory pilot study to examine functional activation and connectivity in SCI patients with chronic NP compared to SCI patients without NP. We developed a novel somatosensory attention task to identify short term fluctuations in neural activity related to NP vs. non-painful somatosensation using functional magnetic resonance imaging (fMRI). We also collected high-resolution resting state fMRI to identify connectivity-based correlations over time between the two groups. We observed increased activation during focus on NP in brain regions associated with somatosensory integration and representational knowledge in pain subjects when compared with controls. Similarly, NP subjects showed increased connectivity at rest in many of the same areas of the brain, with positive correlations between somatomotor networks, the dorsal attention network, and regions associated with pain and specific areas of painful and non-painful sensation within our cohort. Although this pilot analysis did not identify statistically significant differences between groups after correction for multiple comparisons, the observed correlations between NP and functional activation and connectivity align with a priori hypotheses regarding pain, and provide a well-controlled preliminary basis for future research in this severely understudied patient population. Altogether, this study presents a novel task, identifies regions of increased task-based activation associated with NP after SCI in the insula, prefrontal, and medial inferior parietal cortices, and identifies similar regions of increased functional connectivity associated with NP after SCI in sensorimotor, cingulate, prefrontal, and inferior medial parietal cortices. This, along with our complementary results from a structurally based analysis, provide multi-modal evidence for regions of the brain specific to the SCI cohort as novel areas for further study and potential therapeutic targeting to improve outcomes for NP patients.
Highlights
Neuropathic pain (NP) is a spontaneous, chronic pain condition caused by a lesion or disease of the nervous system [1]
We found no significant differences between groups in any demographic category tested, except marital status for which the pain group had a higher proportion of married subjects
Our results indicate a positive relationship between NP after spinal cord injury (SCI) and neurological activity in insular, cingulate, somatosensory, medial prefrontal, and inferior medial parietal areas of cerebral cortex
Summary
Neuropathic pain (NP) is a spontaneous, chronic pain condition caused by a lesion or disease of the nervous system [1]. NP remains complex and difficult to treat for the SCI patient population, due in part to other secondary conditions of SCI and a lack of a physiological mechanistic understanding of NP in general [4]. A majority of past NP studies have used healthy, ambulatory control populations. SCI itself is known to result in functional and structural reorganization within the central nervous system [5,6,7,8,9,10], limiting our ability to draw strong conclusions from these studies with healthy controls. There are a growing number of studies that do compare those who develop NP after SCI to those who do not, a clear understanding of neurological activity related to NP in the SCI population has yet to be developed
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