Advertisement

Structural and Functional Brain Changes at Early and Late Stages of Complex Regional Pain Syndrome

Published:October 13, 2017DOI:https://doi.org/10.1016/j.jpain.2017.09.007

      Highlights

      • We studied brain changes at early vs late stages of complex regional pain syndrome.
      • Early gray matter volume decrease was found in sensorimotor and parietal cortices.
      • At early stage, cerebral perfusion was reduced in parts of the limbic system.
      • We found higher perfusion in motor cortex but no gray matter changes at late stage.
      • Sensorimotor network changes at both stages showed impairment of motor control.

      Abstract

      Brain plasticity is demonstrated in complex regional pain syndrome (CRPS), although it is unclear how it modulates at different stages of CRPS. The observation that symptoms can progress over time suggests that the pattern of brain changes might also evolve. We measured structural and functional changes as well as sensorimotor integration at the early stage (ES) and late stage (LS) of CRPS. Twelve ES patients, 16 LS patients, and 16 age- and sex-matched controls were recruited. Gray matter (GM) volume was estimated using voxel-based morphometry. Cerebral perfusion was measured using arterial spin labeling, because it provides a measure of resting neural activity. Connectivity to sensorimotor regions was evaluated using blood-oxygen level-dependent images. The ES group showed reduced GM volume and perfusion in areas associated with spatial body perception, somatosensory cortex, and the limbic system, whereas the LS group exhibited increased perfusion in the motor cortex but no changes in GM volume. However, in the LS group, GM volume in areas associated with pain processing was negatively correlated with average pain levels, likely reflecting a response to ongoing pain. Furthermore, connectivity to sensorimotor cortex showed disruptions in regions associated with motor control and planning, implying impairment of higher-order motor control.

      Perspective

      This article presents brain changes at ES and LS of CRPS. We found different patterns of brain changes between these 2 stages. Understanding modulation of brain plasticity at different stages of CRPS could help understand the diversity in outcomes and treatment response and hopefully improve treatment planning.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ackerman W.E.
        • Zhang J.M.
        Efficacy of stellate ganglion blockade for the management of type 1 complex regional pain syndrome.
        South Med J. 2006; 99: 1084-1088
        • Ashburner J.
        A fast diffeomorphic image registration algorithm.
        Neuroimage. 2007; 38: 95-113
        • Ashburner J.
        • Friston K.J.
        Voxel-based morphometry—The methods.
        Neuroimage. 2000; 11: 805-821
        • Baliki M.N.
        • Mansour A.R.
        • Baria A.T.
        • Apkarian A.V.
        Functional reorganization of the default mode network across chronic pain conditions.
        PLoS One. 2014; 9 (e106133)
        • Baliki M.N.
        • Schnitzer T.J.
        • Bauer W.R.
        • Apkarian A.V.
        Brain morphological signatures for chronic pain.
        PLoS One. 2011; 6 (e26010)
        • Bank P.J.
        • Peper C.E.
        • Marinus J.
        • van Hilten J.J.
        • Beek P.J.
        Intended and unintended (sensory-)motor coupling between the affected and unaffected upper limb in complex regional pain syndrome.
        Eur J Pain. 2015; 19: 1021-1034
        • Barad M.J.
        • Ueno T.
        • Younger J.
        • Chatterjee N.
        • Mackey S.
        Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain.
        J Pain. 2014; 15: 197-203
        • Bean D.J.
        • Johnson M.H.
        • Kydd R.R.
        The outcome of complex regional pain syndrome type 1: A systematic review.
        J Pain. 2014; 15: 677-690
        • Becerra L.
        • Sava S.
        • Simons L.E.
        • Drosos A.M.
        • Sethna N.
        • Berde C.
        • Lebel A.A.
        • Borsook D.
        Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome.
        Neuroimage Clin. 2014; 6: 347-369
        • Behzadi Y.
        • Restom K.
        • Liau J.
        • Liu T.T.
        A component based noise correction method (CompCor) for BOLD and perfusion based fMRI.
        Neuroimage. 2007; 37: 90-101
        • Birklein F.
        • O'Neill D.
        • Schlereth T.
        Complex regional pain syndrome an optimistic perspective.
        Neurology. 2014; 84: 89-96
        • Birklein F.
        • Schlereth T.
        Complex regional pain syndrome—Significant progress in understanding.
        Pain. 2015; 156: 94-103
        • Bolwerk A.
        • Seifert F.
        • Maihöfner C.
        Altered resting-state functional connectivity in complex regional pain syndrome.
        J Pain. 2013; 14: 1107-1115
        • Bonica J.
        Causalgia and other reflex sympathetic dystrophies.
        in: Bonica J. Loeser J. Chapman C. Fordyce W. The Management of Pain. 2nd ed. Lea & Febiger London, Philadelphia1990: 220-243
        • Borghammer P.
        • Cumming P.
        • Aanerud J.
        • Gjedde A.
        Artefactual subcortical hyperperfusion in PET studies normalized to global mean: Lessons from Parkinson's disease.
        Neuroimage. 2009; 45: 249-257
        • Bruehl S.
        • Harden R.N.
        • Galer B.S.
        • Saltz S.
        • Backonja M.
        • Stanton-Hicks M.
        Complex regional pain syndrome: Are there distinct subtypes and sequential stages of the syndrome?.
        Pain. 2002; 95: 119-124
        • Bushnell M.C.
        • Čeko M.
        • Low L.A.
        Cognitive and emotional control of pain and its disruption in chronic pain.
        Nat Rev Neurosci. 2013; 14: 502-511
        • Cleeland C.
        • Ryan K.
        Pain assessment: Global use of the Brief Pain Inventory.
        Ann Acad Med Singapore. 1994; 23: 129-138
        • Dai W.
        • Garcia D.
        • de Bazelaire C.
        • Alsop D.C.
        Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields.
        Magn Reson Med. 2008; 60: 1488-1497
        • Eickhoff S.B.
        • Amunts K.
        • Mohlberg H.
        • Zilles K.
        The human parietal operculum. II. Stereotaxic maps and correlation with functional imaging results.
        Cereb Cortex. 2006; 16: 268-279
        • Eickhoff S.B.
        • Schleicher A.
        • Zilles K.
        • Amunts K.
        The human parietal operculum. I. Cytoarchitectonic mapping of subdivisions.
        Cereb Cortex. 2006; 16: 254-267
        • Fairbank J.C.
        • Pynsent P.B.
        The Oswestry Disability Index.
        Spine. 2000; 25: 2940-2953
        • Feinberg D.A.
        • Günther M.
        Cerebral blood flow imaging with 3D GRASE ASL sequence increases SNR and shortens acquisition time.
        MAGNETOM Flash. 2009; : 62-69
        • Fernández-Seara M.A.
        • Wang Z.
        • Wang J.
        • Rao H.Y.
        • Guenther M.
        • Feinberg D.A.
        • Detre J.A.
        Continuous arterial spin labeling perfusion measurements using single shot 3D GRASE at 3 T.
        Magn Reson Med. 2005; 54: 1241-1247
        • Fukumoto M.
        • Ushida T.
        • Zinchuk V.S.
        Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Reduced bone formation after exposure to organophosphates.
        Lancet. 1999; 354: 1790-1791
        • Geha P.Y.
        • Baliki M.N.
        • Harden R.N.
        • Bauer W.R.
        • Parrish T.B.
        • Apkarian A.V.
        The brain in chronic CRPS pain: Abnormal gray-white matter interactions in emotional and autonomic regions.
        Neuron. 2008; 60: 570-581
        • Geyer S.
        • Ledberg A.
        • Schleicher A.
        • Kinomura S.
        • Schormann T.
        • Bürgel U.
        • Klingberg T.
        • Larsson J.
        • Zilles K.
        • Roland P.E.
        Two different areas within the primary motor cortex of man.
        Nature. 1996; 382: 805-807
        • Geyer S.
        • Schleicher A.
        • Zilles K.
        Areas 3a, 3b, and 1 of human primary somatosensory cortex.
        Neuroimage. 1999; 10: 63-83
        • Grefkes C.
        • Geyer S.
        • Schormann T.
        • Roland P.
        • Zilles K.
        Human somatosensory area 2: Observer-independent cytoarchitectonic mapping, interindividual variability, and population map.
        Neuroimage. 2001; 14: 617-631
        • Harden R.N.
        • Bruehl S.
        • Galer B.S.
        • Saltz S.
        • Bertram M.
        • Backonja M.
        • Gayles R.
        • Rudin N.
        • Bhugra M.K.
        • Stanton-Hicks M.
        Complex regional pain syndrome: Are the IASP diagnostic criteria valid and sufficiently comprehensive?.
        Pain. 1999; 83: 211-219
        • Harden R.N.
        • Oaklander A.L.
        • Burton A.W.
        • Perez R.S.
        • Richardson K.
        • Swan M.
        • Barthel J.
        • Costa B.
        • Graciosa J.R.
        • Bruehl S.
        Complex regional pain syndrome: Practical diagnostic and treatment guidelines.
        Pain Med. 2013; 14: 180-229
        • Hashmi J.A.
        • Baliki M.N.
        • Huang L.
        • Baria A.T.
        • Torbey S.
        • Hermann K.M.
        • Schnitzer T.J.
        • Apkarian A.V.
        Shape shifting pain: Chronification of back pain shifts brain representation from nociceptive to emotional circuits.
        Brain. 2013; 136: 2751-2768
        • Howard M.A.
        • Sanders D.
        • Krause K.
        • O'Muircheartaigh J.
        • Fotopoulou A.
        • Zelaya F.
        • Thacker M.
        • Massat N.
        • Huggins J.P.
        • Vennart W.
        • Choy E.
        • Daniels M.
        • Williams S.C.
        Alterations in resting-state regional cerebral blood flow demonstrate ongoing pain in osteoarthritis: An arterial spin-labeled magnetic resonance imaging study.
        Arthritis Rheum. 2012; 64: 3936-3946
        • Ji G.
        • Neugebauer V.
        Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABA A receptors.
        J Neurophysiol. 2011; 106: 2642-2652
        • Jorge L.L.
        • Amaro E.
        Brain imaging in fibromyalgia.
        Curr Pain Headache Rep. 2012; 16: 388-398
        • Karnath H.O.
        Spatial orientation and the representation of space with parietal lobe lesions.
        Philos Trans R Soc Lond B Biol Sci. 1997; 352: 1411-1419
        • Kato Y.
        • Araki N.
        • Matsuda H.
        • Ito Y.
        • Suzuki C.
        Arterial spin-labeled MRI study of migraine attacks treated with rizatriptan.
        J Headache Pain. 2010; 11: 255-258
        • Klega A.
        • Eberle T.
        • Buchholz H.G.
        • Maus S.
        • Maihofner C.
        • Schreckenberger M.
        • Birklein F.
        Central opioidergic neurotransmission in complex regional pain syndrome.
        Neurology. 2010; 75: 129-136
        • Kucyi A.
        • Moayedi M.
        • Weissman-Fogel I.
        • Goldberg M.B.
        • Freeman V, B.
        • Tenenbaum H.C.
        • Davis K.D.
        Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination.
        J Neurosci. 2014; 34: 3969-3975
        • Lee D.H.
        • Lee K.J.
        • Cho K.I.
        • Noh E.C.
        • Jang J.H.
        • Kim Y.C.
        • Kang D.H.
        Brain alterations and neurocognitive dysfunction in patients with complex regional pain syndrome.
        J Pain. 2015; 16: 580-586
        • Lewis J.S.
        • Kersten P.
        • McCabe C.S.
        • McPherson K.M.
        • Blake D.R.
        Body perception disturbance: A contribution to pain in complex regional pain syndrome (CRPS).
        Pain. 2007; 133: 111-119
        • Liu J.
        • Hao Y.
        • Du M.
        • Wang X.
        • Zhang J.
        • Manor B.
        • Jiang X.
        • Fang W.
        • Wang D.
        Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: A perfusion fMRI study.
        Pain. 2013; 154: 110-118
        • Maihöfner C.
        • Baron R.
        • DeCol R.
        • Binder A.
        • Birklein F.
        • Deuschl G.
        • Handwerker H.O.
        • Schattschneider J.
        The motor system shows adaptive changes in complex regional pain syndrome.
        Brain. 2007; 130: 2671-2687
        • Maihöfner C.
        • Seifert F.
        • Markovic K.
        Complex regional pain syndromes: New pathophysiological concepts and therapies.
        Eur J Neurol. 2010; 17: 649-660
        • Maleki J.
        • LeBel A.
        • Bennett G.
        • Schwartzman R.
        Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy).
        Pain. 2000; 88: 259-266
        • Oshio R.
        • Tanaka S.
        • Sadato N.
        • Sokabe M.
        • Hanakawa T.
        • Honda M.
        Differential effect of double-pulse TMS applied to dorsal premotor cortex and precuneus during internal operation of visuospatial information.
        Neuroimage. 2010; 49: 1108-1115
        • Owen D.G.
        • Clarke C.F.
        • Bureau Y.
        • Ganapathy S.
        • Prato F.S.
        • St Lawrence K.S.
        Measuring the neural response to continuous intramuscular infusion of hypertonic saline by perfusion MRI.
        J Magn Reson Imaging. 2012; 35: 669-677
        • Pleger B.
        • Draganski B.
        • Schwenkreis P.
        • Lenz M.
        • Nicolas V.
        • Maier C.
        • Tegenthoff M.
        Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.
        PLoS One. 2014; 9 (e85372)
        • Reinersmann A.
        • Landwehrt J.
        • Krumova E.K.
        • Ocklenburg S.
        • Güntürkün O.
        • Maier C.
        Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I).
        Pain. 2012; 153: 2174-2181
        • Rockett M.
        Diagnosis, mechanisms and treatment of complex regional pain syndrome.
        Curr Opin Anaesthesiol. 2014; 27: 494-500
        • Schwenkreis P.
        • Janssen F.
        • Rommel O.
        Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand.
        Neurology. 2003; 61: 515-519
        • Schwenkreis P.
        • Maier C.
        • Tegenthoff M.
        Functional imaging of central nervous system involvement in complex regional pain syndrome.
        AJNR Am J Neuroradiol. 2009; 30: 1279-1284
        • Shiraishi S.
        • Kobayashi H.
        • Nihashi T.
        • Kato K.
        • Iwano S.
        • Nishino M.
        • Ishigaki T.
        • Ikeda M.
        • Kato T.
        • Ito K.
        • Kimura T.
        Cerebral glucose metabolism change in patients with complex regional pain syndrome: A PET study.
        Radiat Med. 2006; 24: 335-344
        • Sumitani M.
        • Rossetti Y.
        • Shibata M.
        • Matsuda Y.
        • Sakaue G.
        • Inoue T.
        • Mashimo T.
        • Miyauchi S.
        Prism adaptation to optical deviation alleviates pathologic pain.
        Neurology. 2007; 68: 128-133
        • Ushida T.
        • Fukumoto M.
        • Binti C.
        • Ikemoto T.
        • Taniguchi S.
        • Ikeuchi M.
        • Nishihara M.
        • Tani T.
        Alterations of contralateral thalamic perfusion in neuropathic pain.
        Open Neuroimag J. 2010; 4: 182-186
        • van Rijn M.A.
        • Marinus J.
        • Putter H.
        • Bosselaar S.R.
        • Moseley G.L.
        • van Hilten J.J.
        Spreading of complex regional pain syndrome: Not a random process.
        J Neural Transm. 2011; 118: 1301-1309
        • van Velzen G.A.
        • Rombouts S.A.
        • van Buchem M.A.
        • Marinus J.
        • van Hilten J.J.
        Is the brain of complex regional pain syndrome patients truly different?.
        Eur J Pain. 2016; 20: 1622-1633
        • Wang J.
        • Alsop D.C.
        • Song H.K.
        • Maldjian J.A.
        • Tang K.
        • Salvucci A.E.
        • Detre J.A.
        Arterial transit time imaging with flow encoding arterial spin tagging (FEAST).
        Magn Reson Med. 2003; 50: 599-607
        • Wasan A.D.
        • Loggia M.L.
        • Chen L.Q.
        • Napadow V.
        • Kong J.
        • Gollub R.L.
        Neural correlates of chronic low back pain measured by arterial spin labeling.
        Anesthesiology. 2011; 115: 364-374
        • Wenderoth N.
        • Debaere F.
        • Sunaert S.
        • Swinnen S.P.
        The role of anterior cingulate cortex and precuneus in the coordination of motor behaviour.
        Eur J Neurosci. 2005; 22: 235-246
        • Wu W.C.
        • Fernández-Seara M.
        • Detre J.A.
        • Wehrli F.W.
        • Wang J.
        A theoretical and experimental investigation of the tagging efficiency of pseudocontinuous arterial spin labeling.
        Magn Reson Med. 2007; 58: 1020-1027
        • Ye F.Q.
        • Frank J.A.
        • Weinberger D.R.
        • McLaughlin A.C.
        Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST).
        Magn Reson Med. 2000; 44: 92-100