Identifying brain regions associated with the neuropathology of chronic low back pain: a resting-state amplitude of low-frequency fluctuation study.

BACKGROUND Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes. METHODS We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres. RESULTS ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre. CONCLUSIONS Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.

[1]  The use of neuroimaging to advance the understanding of chronic pain: from description to mechanism. , 2014, Psychosomatic medicine.

[2]  Bart Rypma,et al.  Regional homogeneity of resting-state fMRI contributes to both neurovascular and task activation variations. , 2013, Magnetic resonance imaging.

[3]  R. Deyo,et al.  Opioids for low back pain , 2015, BMJ : British Medical Journal.

[4]  J. Kong,et al.  Neurochemical changes in patients with chronic low back pain detected by proton magnetic resonance spectroscopy: A systematic review , 2016, NeuroImage: Clinical.

[5]  Bruce Fischl,et al.  FreeSurfer , 2012, NeuroImage.

[6]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[7]  G. Lewis,et al.  Is Motor Cortical Excitability Altered in People with Chronic Pain? A Systematic Review and Meta-Analysis , 2016, Brain Stimulation.

[8]  Martin Underwood,et al.  What low back pain is and why we need to pay attention , 2018, The Lancet.

[9]  Emeran A. Mayer,et al.  Preliminary structural MRI based brain classification of chronic pelvic pain: A MAPP network study , 2014, PAIN®.

[10]  P. Croft,et al.  Classification of Low Back Pain in Primary Care: Using “Bothersomeness” to Identify the Most Severe Cases , 2005, Spine.

[11]  Bin Lu,et al.  Reproducibility of R‐fMRI metrics on the impact of different strategies for multiple comparison correction and sample sizes , 2018, Human brain mapping.

[12]  Yihong Yang,et al.  Static and dynamic characteristics of cerebral blood flow during the resting state , 2009, NeuroImage.

[13]  Peter Fransson,et al.  Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. , 2013, Arthritis and rheumatism.

[14]  Bilwaj Gaonkar,et al.  Control-group feature normalization for multivariate pattern analysis of structural MRI data using the support vector machine , 2016, NeuroImage.

[15]  Yun Jiao,et al.  MRI assessment of amplitude of low-frequency fluctuation in rat brains with acute cerebral ischemic stroke , 2012, Neuroscience Letters.

[16]  J. Nabekura,et al.  Functional and structural plasticity in the primary somatosensory cortex associated with chronic pain , 2017, Journal of neurochemistry.

[17]  J. Downar,et al.  A multimodal cortical network for the detection of changes in the sensory environment , 2000, Nature Neuroscience.

[18]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[19]  Ying Li,et al.  Acupuncture modulates the abnormal brainstem activity in migraine without aura patients , 2017, NeuroImage: Clinical.

[20]  V. Ramachandran,et al.  The perception of phantom limbs. The D. O. Hebb lecture. , 1998, Brain : a journal of neurology.

[21]  V. Napadow,et al.  Disrupted functional connectivity of the periaqueductal gray in chronic low back pain , 2014, NeuroImage: Clinical.

[22]  L. Uddin Salience processing and insular cortical function and dysfunction , 2014, Nature Reviews Neuroscience.

[23]  Min Zhuo,et al.  Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain , 2016, Nature Reviews Neuroscience.

[24]  B. Cagnie,et al.  Structural and functional brain abnormalities in chronic low back pain: A systematic review. , 2015, Seminars in arthritis and rheumatism.

[25]  Matthew D. Lieberman,et al.  The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference , 2015, Proceedings of the National Academy of Sciences.

[26]  Pascal Tétreault,et al.  Corticolimbic anatomical characteristics predetermine risk for chronic pain. , 2016, Brain : a journal of neurology.

[27]  Gian Domenico Iannetti,et al.  Alpha and gamma oscillation amplitudes synergistically predict the perception of forthcoming nociceptive stimuli , 2015, Human brain mapping.

[28]  M. Lindquist,et al.  An fMRI-based neurologic signature of physical pain. , 2013, The New England journal of medicine.

[29]  Irene Tracey,et al.  The Cerebral Signature for Pain Perception and Its Modulation , 2007, Neuron.

[30]  Justin L. Vincent,et al.  Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Fields State-dependent opioid control of pain , 2004, Nature Reviews Neuroscience.

[32]  R. Cameron Craddock,et al.  A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics , 2013, NeuroImage.

[33]  P. Khalsa,et al.  A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain. , 2009, Archives of internal medicine.

[34]  K. Davis,et al.  Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks , 2013, Proceedings of the National Academy of Sciences.

[35]  Mikko Sams,et al.  Neuroanatomical substrate of noise sensitivity , 2018, NeuroImage.

[36]  Stephen M. Smith,et al.  Faster permutation inference in brain imaging , 2016, NeuroImage.

[37]  V. Napadow,et al.  Neural Correlates of Chronic Low Back Pain Measured by Arterial Spin Labeling , 2011, Anesthesiology.

[38]  Kevin A. Johnson,et al.  Multivariate classification of structural MRI data detects chronic low back pain. , 2014, Cerebral cortex.

[39]  H. Flor,et al.  Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations , 2017, Nature Reviews Neurology.

[40]  Ishtiaq Mawla,et al.  Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain. , 2019, Pain.