Highlights
- •Pain severity after MVC predicted by resting state functional connectivity
- •Positive dACC-premotor connectivity predicts greater pain severity
- •Negative dACC-precuneus connectivity predicts greater pain severity
Abstract
There is significant heterogeneity in pain outcomes following motor vehicle crashes
(MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain
months after injury while others recover. Despite variable outcomes, the pathogenesis
of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal
anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting
state functional magnetic resonance imaging studies find increased functional connectivity
(FC) between the dACC and regions involved in pain processing in those with chronic
pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore
relate to pain severity. The present study completed rsfMRI scans on N = 22 survivors
of MVCs collected within 2 weeks of the incident to test whole-brain dACC-FC as a
predictor of pain severity 6 months later. At 2 weeks, pain symptoms were predicted
by positive connectivity between the dACC and the premotor cortex. Controlling for
pain symptoms at 2 weeks, pain symptoms at 6 months were predicted by negative connectivity
between the dACC and the precuneus. Previous research implicates the precuneus in
the individual subjective awareness of pain. Given a relatively small sample size,
approximately half of which did not experience chronic pain at 6 months, findings
warrant replication. Nevertheless, this study provides preliminary evidence of enhanced
dACC connectivity with motor regions and decreased connectivity with pain processing
regions as immediate and prospective predictors of pain following MVC.
Perspective
This article presents evidence of distinct neural vulnerabilities that predict chronic
pain in MVC survivors based on whole-brain connectivity with the dorsal anterior cingulate
cortex.
Key words
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References
- Prefrontal cortical projections to longitudinal columns in the midbrain periaqueductal gray in Macaque monkeys.J Comp Neurol. 1998; 401: 455-479
- Human brain mechanisms of pain perception and regulation in health and disease.Eur J Pain. 2005; 9: 463
- PTSD and the experience of pain: Research and clinical implications of shared vulnerability and mutual maintenance models.Can J Psychiatry. 2002; 47: 930-937
- Functional reorganization of the default mode network across chronic pain conditions.PLoS One. 2014; 9e106133
- Corticostriatal functional connectivity predicts transition to chronic back pain.Nat Neurosci. 2012; 15: 1117-1119
- Cellular and molecular mechanisms of pain.Cell. 2009; 139: 267-284
- Assessment and treatment of posttraumatic stress disorder after a motor vehicle collision: Empirical findings and clinical observations.Prof Psychol Res Pr. 2007; 38: 629-639
- Altered resting-state functional connectivity in complex regional pain syndrome.J Pain. 2013; 14: 1107-1115.e8
- Pain distribution and predictors of widespread pain in the immediate aftermath of motor vehicle collision: Widespread pain after motor vehicle collision.Eur J Pain. 2013; 17: 1243-1251
- From nociception to pain perception: Imaging the spinal and supraspinal pathways.J Anat. 2005; 207: 19-33
- The brain's default network: anatomy, function, and relevance to disease.Ann N Y Acad Sci. 2008; 1124: 1-38
- Cognitive and emotional influences in anterior cingulate cortex.Trends Cogn Sci. 2000; 4: 215-222
- Cognitive and emotional control of pain and its disruption in chronic pain.Nat Rev Neurosci. 2013; 14: 502-511
- The precuneus: A review of its functional anatomy and behavioural correlates.Brain. 2006; 129: 564-583
- Altered primary motor cortex structure, organization, and function in chronic pain: A systematic review and meta-analysis.J Pain. 2018; 19: 341-359
- Will this patient develop persistent disabling low back pain?.JAMA. 2010; 303: 1295-1302
- Disrupted functional connectivity of the pain network in fibromyalgia.Psychosom Med. 2012; 74: 55-62
- Design and reporting characteristics of clinical trials of select chronic and recurrent pediatric pain conditions: An analgesic, anesthetic, and addiction clinical trial translations, innovations, opportunities, and networks systematic review.J Pain. 2019; 20: 394-404
- Functional imaging of pain in patients with primary fibromyalgia.J Rheumatol. 2004; 31: 364-378
- The exercising brain: changes in functional connectivity induced by an integrated multimodal cognitive and whole-body coordination training.Neural Plast. 2016; 2016: 1-11
- Traumatic injury in the United States: In-patient epidemiology 2000–2011.Injury. 2016; 47: 1393-1403
- Studies with pain rating scales.Ann Rheum Dis. 1978; 37: 378-381
- Chronic pain and posttraumatic stress symptoms in litigating motor vehicle accident victims.Clin J Pain. 2005; 21: 251-261
- A review of chronic pain impact on patients, their social environment and the health care system.J Pain Res. 2016; 9: 457-467
- The spinothalamic system targets motor and sensory areas in the cerebral cortex of monkeys.J Neurosci. 2009; 29: 14223-14235
- Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates.Proc Natl Acad Sci U S A. 2016; 113: 7900-7905
- Emotional processing in anterior cingulate and medial prefrontal cortex.Trends Cogn Sci. 2011; 15: 85-93
- The neurobiology of pain perception in normal and persistent pain.Pain. 2015; : 22
- Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis.J Rheumatol. 1990; 17: 1022-1024
- Functional neuroanatomy of emotion and its regulation in PTSD.Harv Rev Psychiatry. 2018; 26: 116-128
- The human brain is intrinsically organized into dynamic, anticorrelated functional networks.PNAS. 2005; 102: 9673-9678
- The anterior cingulate cortex and pain processing.Front Integr Neurosci. 2014; 8 (Available at:)http://journal.frontiersin.org/article/10.3389/fnint.2014.00035/abstractDate accessed: August 12, 2020
- Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula.eLife. 2017; 6 (Available at:)https://elifesciences.org/articles/24770Date accessed: August 12, 2020
- Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.Neuroimage. 2007; 34: 905-923
- Evidence of augmented central pain processing in idiopathic chronic low back pain.Arthr Rheum. 2004; 50: 613-623
- Individual differences in pain sensitivity vary as a function of precuneus reactivity.Brain Topogr. 2014; 27: 366-374
- Pain catastrophizing and neural responses to pain among persons with fibromyalgia.Brain. 2004; 127: 835-843
- Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis.Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 1201-1213
- Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain.J Neurosci. 2014; 34: 14252-14259
- Resting state functional connectivity of the amygdala and problem drinking in non-dependent alcohol drinkers.Drug Alcohol Depend. 2018; 185: 173-180
- Pain-related neurons in the human cingulate cortex.Nat Neurosci. 1999; 2: 403-405
- Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation.Eur J Pain. 2016; 20: 1079-1089
- Anterior cingulate cortical neuronal activity during perception of noxious thermal stimuli in monkeys.J Neurophysiol. 2005; 94: 1980-1991
- Distinct regions within medial prefrontal cortex process pain and cognition.J Neurosci. 2016; 36: 12385-12392
- FSL.Neuroimage. 2012; 62: 782-790
- Dissociating medial frontal and posterior cingulate activity during self-reflection.Soc Cogn Affect Neurosci. 2006; 1: 56-64
- Role of road traffic accidents and other traumatic events in the onset of chronic widespread pain: Results from a population-based prospective study.Arthr Care Res. 2011; 63: 696-701
- Simultaneous resting-state functional MRI and electroencephalography recordings of functional connectivity in patients with schizophrenia: rsfMRI-EEG of FC in schizophrenia.Psychiatry Clin Neurosci. 2017; 71: 262-270
- Intrinsic functional connectivity of the periaqueductal gray, a resting fMRI study.Behav Brain Res. 2010; 211: 215-219
- Nociceptive neurons in the macaque anterior cingulate activate during anticipation of pain.Neuroreport. 1998; 9: 2663-2667
- Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination.J Neurosci. 2014; 34: 3969-3975
- The pain matrix reloaded.Prog Neurobiol. 2011; 93: 111-124
- A direct brainstem–amygdala–cortical ‘alarm’ system for subliminal signals of fear.Neuroimage. 2005; 24: 235-243
- The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference.Proc Natl Acad Sci. 2015; 112: 15250-15255
- An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets.Neuroimage. 2003; 19: 1233-1239
- Clinical applications of visual analogue scales: A critical review.Psychol Med. 1988; 18: 1007-1019
- Incidence and predictors of neck and widespread pain after motor vehicle collision among US litigants and nonlitigants.Pain. 2014; 155: 309-321
- Saliency, switching, attention and control: a network model of insula function.Brain Struct Funct. 2010; 214: 655-667
- Anatomy, physiology and neurobiology of the nociception: A focus on low back pain (part A).Neurochirurgie. 2015; 61: S22-S34
- The relationship between PTSD and chronic pain: Mediating role of coping strategies and depression.Pain. 2013; 154: 609-616
- Amygdala interconnections with the cingulate motor cortex in the rhesus monkey.J Comp Neurol. 2007; 500: 134-165
- Functional imaging of brain responses to pain. A review and meta-analysis.Clin Neurophysiol. 2000; 30: 263-288
- Scanning the horizon: Towards transparent and reproducible neuroimaging research.Nat Rev Neurosci. 2017; 18: 115-126
- Methods to detect, characterize, and remove motion artifact in resting state fMRI.Neuroimage. 2014; 84: 320-341
- Recent progress and outstanding issues in motion correction in resting state fMRI.Neuroimage. 2015; 105: 536-551
- Mapping brain response to pain in fibromyalgia patients using temporal analysis of fMRI.PLoS One. 2009; 4: e5224
- Neurocircuitry models of posttraumatic stress disorder and extinction: Human neuroimaging research—Past, present, and future.Biol Psychiatry. 2006; 60: 376-382
- Functional connectivity of the human amygdala using resting state fMRI.Neuroimage. 2009; 45: 614-626
- Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.Neurosurg Focus. 2015; 38: E11
- Perceived controllability modulates the neural response to pain.J Neurosci. 2004; 24: 7199-8203
- Resting state connectivity correlates with drug and placebo response in fibromyalgia patients.Neuroimage. 2014; 6: 252-261
- The integration of negative affect, pain and cognitive control in the cingulate cortex.Nat Rev Neurosci. 2011; 12: 154-167
- Amygdala plasticity and pain.Pain Res Manag. 2017; 2017: 1-12
- The cerebral signature for pain perception and its modulation.Neuron. 2007; 55: 377-391
- Predictors of chronic pain in traumatically injured hospitalized adult patients.J Trauma Nurs. 2014; 21: 50-56
- Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.Neuroimage. 2002; 15: 273-289
- An fMRI-Based neurologic signature of physical pain.N Engl J Med. 2013; 368: 1388-1397
Weiss DS, Marmar CR: The impact of events scale—Revised. Assessing Psychological Trauma and PTSD. New York, NY, Guilford, 1996, pp 399–411
- Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks.Brain Connect. 2012; 2: 125-141
- Cluster-extent based thresholding in fMRI analyses: Pitfalls and recommendations.Neuroimage. 2014; 91: 412-419
- Functional segregation of the human cingulate cortex is confirmed by functional connectivity based neuroanatomical parcellation.Neuroimage. 2011; 54: 2571-2581
Article info
Publication history
Published online: July 28, 2020
Accepted:
July 25,
2020
Received in revised form:
March 26,
2020
Received:
November 12,
2018
Footnotes
Disclosures: All authors report no biomedical financial interests or potential conflicts of interest.
Funding: This work was supported by funds obtained through the Medical College of Wisconsin Injury Research Center funded by the CDC (R49/CE001175).
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© 2020 by United States Association for the Study of Pain, Inc.
