Brain morphological signatures for chronic pain
Marwan N Baliki, Thomas J Schnitzer, William R Bauer, A Vania Apkarian, Marwan N Baliki, Thomas J Schnitzer, William R Bauer, A Vania Apkarian
Abstract
Chronic pain can be understood not only as an altered functional state, but also as a consequence of neuronal plasticity. Here we use in vivo structural MRI to compare global, local, and architectural changes in gray matter properties in patients suffering from chronic back pain (CBP), complex regional pain syndrome (CRPS) and knee osteoarthritis (OA), relative to healthy controls. We find that different chronic pain types exhibit unique anatomical 'brain signatures'. Only the CBP group showed altered whole-brain gray matter volume, while regional gray matter density was distinct for each group. Voxel-wise comparison of gray matter density showed that the impact on the extent of chronicity of pain was localized to a common set of regions across all conditions. When gray matter density was examined for large regions approximating Brodmann areas, it exhibited unique large-scale distributed networks for each group. We derived a barcode, summarized by a single index of within-subject co-variation of gray matter density, which enabled classification of individual brains to their conditions with high accuracy. This index also enabled calculating time constants and asymptotic amplitudes for an exponential increase in brain re-organization with pain chronicity, and showed that brain reorganization with pain chronicity was 6 times slower and twice as large in CBP in comparison to CRPS. The results show an exuberance of brain anatomical reorganization peculiar to each condition and as such reflecting the unique maladaptive physiology of different types of chronic pain.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
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References
- Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413:203–210.
- Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. ProgNeurobiol. 2009;87:81–97.
- Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–484.
- Baliki MN, Geha PY, Apkarian AV, Chialvo DR. Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci. 2008;28:1398–1403.
- Tagliazucchi E, Balenzuela P, Fraiman D, Chialvo DR. Brain resting state is disrupted in chronic back pain patients. Neurosci Lett. 2010;485:26–31.
- Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, et al. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62:2545–2555.
- Cauda F, Sacco K, Duca S, Cocito D, D'Agata F, et al. Altered resting state in diabetic neuropathic pain. PLoS One. 2009;4:e4542.
- Baliki MN, Geha PY, Fields HL, Apkarian AV. Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron. 2010;66:149–160.
- Apkarian AV, Sosa Y, Sonty S, Levy RE, Harden RN, et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24:10410–10415.
- Schmidt-Wilcke T, Leinisch E, Ganssbauer S, Draganski B, Bogdahn U, et al. Pain; 2006. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients.
- Schmidt-Wilcke T, Luerding R, Weigand T, Jurgens T, Schuierer G, et al. Striatal grey matter increase in patients suffering from fibromyalgia–a voxel-based morphometry study. Pain. 2007;132(Suppl 1):S109–S116.
- Kuchinad A, Schweinhardt P, Seminowicz DA, Wood PB, Chizh BA, et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci. 2007;27:4004–4007.
- Hsu MC, Harris RE, Sundgren PC, Welsh RC, Fernandes CR, et al. No consistent difference in gray matter volume between individuals with fibromyalgia and age-matched healthy subjects when controlling for affective disorder. Pain. 2009;143:262–267.
- Luerding R, Weigand T, Bogdahn U, Schmidt-Wilcke T. Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction. Brain. 2008;131:3222–3231.
- Geha PY, Baliki MN, Harden RN, Bauer WR, Parrish TB, et al. The brain in chronic CRPS pain: abnormal gray-white matter interactions in emotional and autonomic regions. Neuron. 2008;60:570–581.
- Rodriguez-Raecke R, Niemeier A, Ihle K, Ruether W, May A. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. J Neurosci. 2009;29:13746–13750.
- Gwilym SE, Keltner JR, Warnaby CE, Carr AJ, Chizh B, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61:1226–1234.
- Davis KD, Wood ML, Crawley AP, Mikulis DJ. fMRI of human somatosensory and cingulate cortex during painful electrical nerve stimulation. Neuroreport. 1995;7:321–325.
- Blankstein U, Chen J, Diamant NE, Davis KD. Altered brain structure in irritable bowel syndrome: potential contributions of pre-existing and disease-driven factors. Gastroenterology. 2010;138:1783–1789.
- Seminowicz DA, Davis KD. Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task. J Neurophysiol. 2007;97:3651–3659.
- Schmidt-Wilcke T, Leinisch E, Straube A, Kampfe N, Draganski B, et al. Gray matter decrease in patients with chronic tension type headache. Neurology. 2005;65:1483–1486.
- Kim JH, Suh SI, Seol HY, Oh K, Seo WK, et al. Regional grey matter changes in patients with migraine: a voxel-based morphometry study. Cephalalgia. 2008;28:598–604.
- Valfre W, Rainero I, Bergui M, Pinessi L. Voxel-based morphometry reveals gray matter abnormalities in migraine. Headache. 2008;48:109–117.
- Schweinhardt P, Kuchinad A, Pukall CF, Bushnell MC. Increased gray matter density in young women with chronic vulvar pain. Pain. 2008;140:411–419.
- Tu CH, Niddam DM, Chao HT, Chen LF, Chen YS, et al. Brain morphological changes associated with cyclic menstrual pain. Pain. 2010;150:462–468.
- Seminowicz DA, Laferriere AL, Millecamps M, Yu JS, Coderre TJ, et al. MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage. 2009;47:1007–1014.
- Metz AE, Yau HJ, Centeno MV, Apkarian AV, Martina M. Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc Natl Acad Sci U S A. 2009;106:2423–2428.
- Schmidt-Wilcke T. Variations in brain volume and regional morphology associated with chronic pain. Curr Rheumatol Rep. 2008;10:467–474.
- May A. New insights into headache: an update on functional and structural imaging findings. Nat Rev Neurol. 2009;5:199–209.
- Obermann M, Nebel K, Schumann C, Holle D, Gizewski ER, et al. Gray matter changes related to chronic posttraumatic headache. Neurology. 2009;73:978–983.
- Apkarian AV. Pain perception in relation to emotional learning. Curr Opin Neurobiol. 2008;18:464–468.
- Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. 2009;87:81–97.
- Salvador R, Suckling J, Coleman MR, Pickard JD, Menon D, et al. Neurophysiological architecture of functional magnetic resonance images of human brain. CerebCortex. 2005;15:1332–1342.
- Bassett DS, Bullmore E, Verchinski BA, Mattay VS, Weinberger DR, et al. Hierarchical organization of human cortical networks in health and schizophrenia. J Neurosci. 2008;28:9239–9248.
- Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage. 2001;14:21–36.
- Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003;23:3295–3301.
- Gwilym SE, Filippini N, Douaud G, Carr AJ, Tracey I. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study. Arthritis Rheum. 2010;62:2930–2940.
- Seminowicz DA, Labus JS, Bueller JA, Tillisch K, Naliboff BD, et al. Regional gray matter density changes in brains of patients with irritable bowel syndrome. Gastroenterology. 2010;139:48–57 e42.
- Ambroggi F, Ishikawa A, Fields HL, Nicola SM. Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons. Neuron. 2008;59:648–661.
- Mayer EA, Bushnell MC, International Association for the Study of Pain. Seattle: IASP Press. xviii,; 2009. Functional pain syndromes: presentation and pathophysiology.580
- Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62:42–52.
- Lerch JP, Worsley K, Shaw WP, Greenstein DK, Lenroot RK, et al. Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI. Neuroimage. 2006;31:993–1003.
- Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci. 2005;8:828–834.
- Wright IC, Sharma T, Ellison ZR, McGuire PK, Friston KJ, et al. Supra-regional brain systems and the neuropathology of schizophrenia. Cereb Cortex. 1999;9:366–378.
- Fields HL. Proceedings of the 11th world congress on pain. Seattle: IASP press; 2006. A motivation-decision model of pain: the role of opioids. pp. 449–459.
- Burgmer M, Gaubitz M, Konrad C, Wrenger M, Hilgart S, et al. Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia. Psychosom Med. 2009;71:566–573.
- Wood PB, Patterson JC, Sunderland JJ, Tainter KH, Glabus MF, et al. Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. J Pain. 2007;8:51–58.
- Harden RN, Weinland SR, Remble TA, Houle TT, Colio S, et al. Medication Quantification Scale Version III: update in medication classes and revised detriment weights by survey of American Pain Society Physicians. J Pain. 2005;6:364–371.
- Smith SM. Fast robust automated brain extraction. HumBrain Mapp. 2002;17:143–155.
- Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23(S1):208–219.
- Ashburner J, Friston KJ. Voxel-based morphometry–the methods. Neuroimage. 2000;11:805–821.
- Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE TransMedImaging. 2001;20:45–57.
- Senjem ML, Gunter JL, Shiung MM, Petersen RC, Jack CR Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease. Neuroimage. 2005;26:600–608.
- Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. HumBrain Mapp. 2002;15:1–25.
- Smith SM, Nichols TE. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage. 2009;44:83–98.
- Rousseeuw PJ, Ruts I, Tukey JW. The bagplot: A bivariate boxplot. American Statistician. 1999;53:382–387.
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