Functional connectivity and structural analysis of trial spinal cord stimulation responders in failed back surgery syndrome.

Peter A Pahapill,Andrew S Nencka,Guangyu Chen,Elsa V Arocho-Quinones,Shi-Jiang Li,Niels Bergsland

doi:10.1371/journal.pone.0228306

Peter A Pahapill, Andrew S Nencka + Show 4 more

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https://doi.org/10.1371/journal.pone.0228306

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Abstract

BackgroundChronic pain has been associated with alterations in brain structure and function that appear dependent on pain phenotype. Functional connectivity (FC) data on chronic back pain (CBP) is limited and based on heterogeneous pain populations. We hypothesize that failed back surgery syndrome (FBSS) patients being considered for spinal cord stimulation (SCS) therapy have altered resting state (RS) FC cross-network patterns that 1) specifically involve emotion and reward/aversion functions and 2) are related to pain scores.MethodsRS functional MRI (fMRI) scans were obtained for 10 FBSS patients who are being considered for but who have not yet undergone implantation of a permanent SCS device and 12 healthy age-matched controls. Seven RS networks were analyzed including the striatum (STM). The Wilcoxon signed-rank test evaluated differences in cross-network FC strength (FCS). Differences in periaqueductal grey (PAG) FC were assessed with seed-based analysis.ResultsCross-network FCS was decreased (p<0.05) between the STM and all other networks in these FBSS patients. There was a negative linear relationship (R2 = 0.76, p<0.0022) between STMFCS index and pain scores. The PAG showed decreased FC with network elements and amygdala but increased FC with the sensorimotor cortex and cingulate gyrus.ConclusionsDecreased FC between STM and other RS networks in FBSS has not been previously reported. This STMFCS index may represent a more objective measure of chronic pain specific to FBSS which may help guide patient selection for SCS and subsequent management.

Highlights

Increasing evidence suggests a critical role of central nervous system (CNS) plasticity in the development and maintenance of chronic low back pain
Understanding altered neural networks implicated in the pathophysiology of chronic low back pain (cLBP), in turn can lead to development of new management strategies
Resting-state (RS) functional connectivity magnetic resonance imaging is a powerful tool for elucidating the areas of the brain involved in cLBP perception and modulation,[1,2,3] as it facilitates study of both local and diffuse functional properties in the undisturbed state of chronic pain and because Resting state (RS) networks (RSNs) are an intrinsic property of the brain found across various behavioral and physiological states.[1, 4]

Summary

Introduction

Increasing evidence suggests a critical role of central nervous system (CNS) plasticity in the development and maintenance of chronic low back pain (cLBP). Resting-state (RS) functional connectivity magnetic resonance imaging (fcMRI) is a powerful tool for elucidating the areas of the brain involved in cLBP perception and modulation,[1,2,3] as it facilitates study of both local and diffuse functional properties in the undisturbed state of chronic pain and because RS networks (RSNs) are an intrinsic property of the brain found across various behavioral and physiological states.[1, 4] Human brain imaging studies have identified potential anatomical and functional biomarkers that differentiate cLBP patients from healthy subjects.[5] Chronification of LBP has been associated with alterations in brain anatomy and function, including a shift in activity from brain regions involved in acute pain to more emotion or reward circuitry.[1,2,3, 5] The reported changes can depend upon 1) the population of chronic pain patients being studied [1, 6] and 2) the duration of pain that the patients have endured.[1, 5, 7] Some of these structural and functional changes that occur with chronification of pain may be reversible with successful treatment.[8,9,10,11]. We hypothesize that failed back surgery syndrome (FBSS) patients being considered for spinal cord stimulation (SCS) therapy have altered resting state (RS) FC cross-network patterns that 1) involve emotion and reward/aversion functions and 2) are related to pain scores.

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