Abstract
Complex regional pain syndrome (CRPS) is a chronic condition that involves significant
hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities
and frequently by motor dysfunction. Although central brain systems are thought to
play a role in the development and maintenance of CRPS, these systems have not been
well characterized. In this study, we used structural magnetic resonance imaging to
characterize differences in gray matter volume between patients with right upper extremity
CRPS and matched controls. Analyses were carried out using a whole brain voxel-based
morphometry approach. The CRPS group showed decreased gray matter volume in several
pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several
aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen
in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with
self-reported pain were then performed on the CRPS group. Pain duration was associated
with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity
was positively correlated with volume in the left posterior hippocampus and left amygdala,
and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings
demonstrate that CRPS is associated with abnormal brain system morphology, particularly
pain-related sensory, affect, motor, and autonomic systems.
Perspective
This paper presents structural changes in the brains of patients with CRPS, helping
us differentiate CRPS from other chronic pain syndromes and furthering our understanding
of this challenging disease.
Key words
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References
- Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.J Neurosci. 2004; 24: 10410-10415
- Somatotopic representation of nociceptive information in the putamen: An event-related fMRI study.Cereb Cortex. 2004; 14: 1340-1345
- Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices.Neuroimage. 2003; 18: 740-748
- Neurological findings in complex regional pain syndromes—Analysis of 145 cases.Acta Neurol Scand. 2000; 101: 262-269
- Altered brain structure in irritable bowel syndrome: Potential contributions of pre-existing and disease-driven factors.Gastroenterology. 2010; 138: 1783-1789
- Neuroanatomical changes associated with pharmacotherapy in posttraumatic stress disorder.Ann N Y Acad Sci. 2004; 1032: 154-157
- Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging.Neuroimage. 2005; 27: 201-209
- Thermosensory activation of insular cortex.Nat Neurosci. 2000; 3: 184-190
- Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) during capsaicin-induced pain: Modulatory effects on motor cortex excitability.Exp Brain Res. 2010; 203: 31-38
- Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine.Brain. 2006; 129: 543-550
- The brain in chronic CRPS pain: Abnormal gray-white matter interactions in emotional and autonomic regions.Neuron. 2008; 60: 570-581
- Altered pain processing in veterans with posttraumatic stress disorder.Arch Gen Psychiatry. 2007; 64: 76-85
- Validation of proposed diagnostic criteria (the “Budapest criteria”) for complex regional pain syndrome.Pain. 2010; 150: 268-274
- Altered central sensorimotor processing in patients with complex regional pain syndrome.Pain. 2002; 98: 315-323
- Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration.Neuroimage. 2009; 46: 786-802
- fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children.Brain. 2008; 131: 1854-1879
- The motor system shows adaptive changes in complex regional pain syndrome.Brain. 2007; 130: 2671-2687
- Brain processing during mechanical hyperalgesia in complex regional pain syndrome: A functional MRI study.Pain. 2005; 114: 93-103
- Functional imaging of allodynia in complex regional pain syndrome.Neurology. 2006; 66: 711-717
- Cortical reorganization during recovery from complex regional pain syndrome.Neurology. 2004; 63: 693-701
- A possible neural basis for stress-induced hyperalgesia.Pain. 2009; 142: 236-244
- Hypothalamic activation in cluster headache attacks.Lancet. 1998; 352: 275-278
- On the language of pain.Anesthesiology. 1971; 34: 50-59
- The anterior cingulate cortex contains distinct areas dissociating external from self-administered painful stimulation: A parametric fMRI study.Pain. 2005; 114: 347-357
- Neural circuits and functional organization of the striatum.J Neurol. 2000; 247: 1-15
- Representation of pain and somatic sensation in the human insula: A study of responses to direct electrical cortical stimulation.Cereb Cortex. 2002; 12: 376-385
- Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I.Exp Brain Res. 2004; 155: 115-119
- Exacerbation of pain by anxiety is associated with activity in a hippocampal network.J Neurosci. 2001; 21: 9896-9903
- Cortical representation of first and second pain sensation in humans.Proc Natl Acad Sci U S A. 2002; 99: 12444-12448
- Pain is associated with regional grey matter reduction in the general population.Pain. 2011; 152: 904-911
- Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity.J Neurosci. 2006; 26: 10789-10795
- The contribution of the putamen to sensory aspects of pain: Insights from structural connectivity and brain lesions.Brain. 2011; 134: 1987-2004
- Patients with pain disorder show gray-matter loss in pain-processing structures: A voxel-based morphometric study.Psychosom Med. 2009; 71: 49-56
- Cingulate nociceptive circuitry and roles in pain processing—The cingulate premotor pain model. Cingulate Neurobiology and Disease.Oxford University Press, New York2009: 311-344
- Pain and emotion interactions in subregions of the cingulate gyrus.Nat Rev Neurosci. 2005; 6: 533-544
- Structural and functional dichotomy of human midcingulate cortex. Eur.J Neurosci. 2003; 18: 3134-3144
- Variations in brain gray matter associated with chronic pain.Curr Rheumatol Rep. 2010; 12: 462-469
- Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems.Pain. 2010; 149: 222-228
- Prescription opioid analgesics rapidly change the human brain.Pain. 2011; 152: 1803-1810
- Individual sensitivity to pain expectancy is related to differential activation of the hippocampus and amygdala.Hum Brain Mapp. 2010; 31: 326-338
Article info
Publication history
Published online: November 11, 2013
Accepted:
October 30,
2013
Received in revised form:
September 27,
2013
Received:
May 11,
2013
Footnotes
M.B. received funding from the American Academy of Neurology Research Training Fellowship, Minneapolis, MN. S.M. reports funding from Rocky Mountain CRPS Foundation, Denver, CO, NIH K24 DA029262, Bethesda, MD, Chris Redlich Pain Research Endowment.
N.C., T.U., and J.Y. have no disclosures.
Supplementary data accompanying this article are available online at www.jpain.org/ and www.sciencedirect.com/.
Identification
Copyright
© 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
