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Imaging and Clinical Evidence of Sensorimotor Problems in CRPS: Utilizing Novel Treatment Approaches

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Abstract

Inflammation and altered autonomic function are diagnostic signs and symptoms of Complex Regional Pain Syndrome. In the acute stages these are commonly at their most florid accompanied by severe pain and reduced function. Understandably this has directed research towards potential peripheral drivers for the causal mechanisms of this condition. In particular this is now focused on the inflammatory process and the potential role of autoantibodies. More subtle changes also occur in terms of altered tactile processing within the affected limb, disturbances in body perception and motor planning problems that become more evident as the condition progresses. Through careful clinical observation and neuro-imaging techniques, these changes are now thought to be associated with altered cortical processing that includes reorganisation of both the motor and sensory maps. Furthermore, there appears to be a close relationship between the intensity of pain experienced and the extent of cortical re-organisation. This increased knowledge around the peripheral and central mechanisms that may be operating in CRPS has been used to inform novel therapeutic approaches. We discuss here the presenting signs and symptoms of CRPS, with particular focus on sensory and motor changes and consider which mechanisms may drive these changes. Finally, we consider the emerging therapeutic options designed to correct these aberrant mechanisms.

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References

  • Blaes F, Schmitz K, Tschernatsch M, Kaps M, Krasenbrink I, Hemplemann G, Brau ME (2004) Autoimmune etiology of complex regional pain syndrome (M. Sudeck). Neurology 63 (9):1734–1736

    Article  PubMed  CAS  Google Scholar 

  • Baron R, Fields L, Jänig W, Kitt C, Levine JD (2002a) National institute of health workshop: reflex sympathetic dystrophy/complex regional pain syndrome-state-of-the-art science. Anaesth Analg 5:1812–1816

    Article  Google Scholar 

  • Baron R, Schattschneider J, Binder A, Siebrecht D, Wasner G (2002b) Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study. Lancet 359:1655–1660

    Article  PubMed  CAS  Google Scholar 

  • Birklein F (2005) Complex regional pain syndrome. J Neurol 252:131–138

    Article  PubMed  Google Scholar 

  • Boggio PS, Amancio EJ, Correa C, Cecilio S, Valasek C, Bajwa Z, Freedman SD, Pascual-Leone A, Edwards DJ, Fregni F (2009) Transcranial DC stimulation coupled with TENS for the treatment of chronic pain. Clin J Pain 25:691–695

    Article  PubMed  Google Scholar 

  • Bruehl S, Chung OY (2006) Psychological and behavioural aspects of complex regional pain syndrome management. Clin J Pain 22:430–437

    Article  PubMed  Google Scholar 

  • Caro X, Winter E (2001) Attention measures improve in fibromyalgia patients receiving EEG biofeedback training: a pilot study. Arthritis Rheum 44(S):71

    Google Scholar 

  • Christensen K, Jensen EM, Noer I (1982) The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 148(8):653–655

    PubMed  CAS  Google Scholar 

  • Cohen H, McCabe CS, Harris N, Blake DR (2009) Clinical evidence of parietal lobe dysfunction in patients with CRPS Type 1. Rheumatology 48(S1):i95

    Google Scholar 

  • Cohen H, Hall J, Harris N, McCabe C, Jänig W, Blake D (2012) Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic Complex Regional Pain Syndrome (CRPS) type I. Eur J Pain

  • Diers M, Christman C, Koeppe C, Ruf M, Flor H (2010) Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. Pain 149:296–304

    Article  PubMed  Google Scholar 

  • Cooper M (2011) Nerve injuries and the fixed dystonias of CRPS. Pain Med 12:842–43

    Article  PubMed  Google Scholar 

  • Drummond PD (2010) Sensory disturbances in complex regional pain syndrome: clinical observations, autonomic interactions, and possible mechanisms. Pain Med 11:1257–1266

    Article  PubMed  Google Scholar 

  • Flor H (2002) The modification of cortical reorganisation and chronic pain by sensory feedback. Appl Psychophysiol Biofeedback 27 (3):215–225

    Article  PubMed  Google Scholar 

  • Flor H, Nikolajsen L, Jensen TS (2006) Phantom limb pain: a case of maladaptive CNS plasticity? Nat Rev Neurosci 7:873–881

    Article  PubMed  CAS  Google Scholar 

  • Forderreuther S, Sailer U, Straube A (2004) Impaired self-perception of the hand in complex regional pain syndrome (CRPS). Pain 110:756–761

    Article  PubMed  CAS  Google Scholar 

  • Freund W, Wunderlich AP, Stuber G, Mayer F, Steffen P, Mentzel M, Weber F, Schmitz B (2010) Different activation of opercular and posterior cingulate cortex in patients with CRPS 1 compared with healthy controls during perception of electrically induced pain: A functional MRI study. Clin J Pain 26:339–347

    Article  PubMed  Google Scholar 

  • Galer BS, Butler S, Jensen MP (1995) Case-reports and hypothesis - a neglect-like syndrome may be responsible for the motor disturbance in reflex sympathetic dystrophy (Complex-Regional-Pain-Syndrome-1). J Pain Symptom Manag 10:385–391

    Article  CAS  Google Scholar 

  • Giraux P, Sirigu A (2003) Illusory movements of the paralyzed limb restore motor cortex activity. NeuroImage 20(S1):S107–11

    Article  PubMed  Google Scholar 

  • Goebel A, Baronowski AP, Maurer K, Ghiai A, McCabe C, Ambler G (2010) Intravenous immunoglobulin treatment of CRPS: A randomised trial. Ann Intern Med 152(3):152–8

    Article  PubMed  Google Scholar 

  • Gradl G, Schürmann M (2005) Sympathetic dysfunction as a temporary phenomenon in acute posttraumatic CRPS I. Clin Auton Res 15:29–34

    Article  PubMed  Google Scholar 

  • Groeneweg JG, Huygen FJ, Heijmans-Antonissen C, Niehof S, Zijlstra FJ (2006) Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1. BMC Musculoskelet Disord 7:91

    Article  PubMed  Google Scholar 

  • Haggard P, Taylor-Clarke M, Kennett S (2003) Tactile perception, cortical representation and the bodily self. Curr Biol 13:R170–R173

    Article  PubMed  CAS  Google Scholar 

  • Haggard P, Wolpert DM (2005) Disorders of body schema. In: Leiguarda R, Freund HJ, Jeannerod M, Hallet M (eds) Higher-order motor disorders: from neuroanatomy and neurobiology to clinical neurology. Oxford University Press, Oxford, pp 261–271

    Google Scholar 

  • Hall J, Harrison S, Harris N, McCabe C, Blake D (2011) Pain and other symptoms of CRPS can be increased by ambiguous visual stimuli—an exploratory study. Europ J Pain 15:17–22

    Article  Google Scholar 

  • Harden RN, Bruehl S, Perez RS et al (2010) Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome. Pain 150(2):268–74

    Article  PubMed  Google Scholar 

  • Hunter JP, Katz J, Davis KD (2003) The effect of tactile and visual sensory inputs on phantom limb awareness. Brain 126:579–589

    Article  PubMed  Google Scholar 

  • Huygen FJ, De Bruijn AG, De Bruin MT, Groeneweg JG, Klein J, Zijistra FJ (2002) Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm 11(1):47–51

    Article  PubMed  CAS  Google Scholar 

  • Ide J, Yamaga M, Kitamura T, Takagi K (1997) Quantitative evaluation of sympathetic nervous system dysfunction in patients with reflex sympathetic dystrophy. J Hand Surg (Br) 22:102–6

    Article  CAS  Google Scholar 

  • Jänig W, Baron R (2006) Is CRPS I a neuropathic pain syndrome? Pain 120:227–229

    Article  PubMed  Google Scholar 

  • Jensen MP, Grierson C, Tracey-Smith V, Bacigalupi SC, Othmer S (2007) Neurofeedback treatment for pain assocoiated with CRPS type 1. J Neuropathy 11(1):45–53

    Google Scholar 

  • Jensen TS, Baron R, Haanpaa M, Kalso E, Loeser JD, Rice ASC, Treede RD (2011) A new definition of neuropathic pain. Pain 152 (10):2204–2205

    Article  PubMed  Google Scholar 

  • Johnson S, Hall J, Barnett S, Draper M, Darbyshire G, Haynes L, Rooney C, Cameron H, Moseley GL, Williams A, McCabe C, Goebel A (2011) Using Graded Motor Imagery for Complex Regional Pain Syndrome in clinical practice: failure to improve pain. Eur J Pain 16(4):550–561

    Article  PubMed  Google Scholar 

  • Juottonen K, Gockel M, Silen T, Hurri H, Hari R, Forss N (2002) Altered central sensorimotor processing in patients with complex regional pain syndrome. Pain 98:315–323

    Article  PubMed  Google Scholar 

  • Kirveskari E, Vartianen NV, Gockel M, Forss N (2010) Motor cortex dysfunction in complex regional pain syndrome. Clin Neurophysiol 121:1085–1091

    Article  PubMed  Google Scholar 

  • Kohr D, Singh P, Tschernatsch M, Kaps M, Pouokam E, Diener M, Kimmer W, Birklein F, Vincent A, Goebel A, Wallukat G, Bales F (2011) Autoimmunity against the β2 adrenergic receptor and muscarine-2 recptor in complex regional pain syndrome. Pain 152:2690–2700

    Article  PubMed  CAS  Google Scholar 

  • Levit-Binnun N, Golland Y (2012) Finding behavioural and network indicators of brain vulnerability. Front Neurosci 6(10):1–9

    Google Scholar 

  • Lewis JS, Kersten P, McCabe CS, McPherson KM, Blake DR (2007) Body perception disturbance: A contribution to pain in Complex Regional Pain Syndrome. Pain 133:111–119

    Article  PubMed  Google Scholar 

  • Lewis JS, Kersten P, McPherson KM, Taylor GJ, Harris N, McCabe CS, Blake DR (2010) Wherever is my arm? Impaired upper limb position accuracy in Complex Regional Pain Syndrome. Pain 149:463–469

    Article  PubMed  Google Scholar 

  • Lewis JS, Schweinhardt P (2012) Perceptions of the painful body: The relationship between body perception disturbance, tactile discrimination and pain in Complex Regional Pain Syndrome. Eur J Pain.

  • Maier C, Baron R, Tolle TR et al (2010) Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain 150:439–450

    Article  PubMed  CAS  Google Scholar 

  • Maihofner C, Handwerker HO, Neundorfer B, Birklein F (2003) Patterns of cortical reorganization in complex regional pain syndrome. Neurology 61:1707–1715

    Article  PubMed  Google Scholar 

  • Maihofner C, Handwerker HO, Neundorfer B, Birklein F (2004) Cortical reorganization during recovery from complex regional pain syndrome. Neurology 63:693–701

    Article  PubMed  Google Scholar 

  • Maihöfner C, Baron R, De Col R et al (2007) The motor system shows adaptive changes in complex regional pain syndrome. Brain 130:2671–2687

    Article  PubMed  Google Scholar 

  • Marinus J, Moseley GL, Birklein F, Baron R, Kingery W, Van Hilten JJ (2011) Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol 10:637–648

    Article  PubMed  Google Scholar 

  • McCabe CS, Haigh RC, Halligan PW, Blake DR (2003a) Referred sensations in complex regional pain syndrome Type 1. Rheumatology 42:1067–1073

    Article  PubMed  CAS  Google Scholar 

  • McCabe CS, Haigh RC, Ring EFR, Halligan PW, Wall PD, Blake DR (2003b) A controlled pilot study of the utility of mirror visual feedback in the treatment of Complex Regional Pain Syndrome (Type 1). Rheumatology 42:97–101

    Article  PubMed  CAS  Google Scholar 

  • McCabe CS, Blake DR (2007) Evidence for a mismatch between the brain’s movement control system and the sensory system as an explanation for some pain-related disorders. Curr Pain Headache Rep 11:104–108

    Article  PubMed  Google Scholar 

  • McCabe CS, Cohen H, Hall J, Lewis J, Rodham K, Harris N (2009) Somatosensory Conflicts in CRPS Type 1 and Fibromyalgia. Curr Rheumatol Rep 11:461–465

    Article  PubMed  Google Scholar 

  • McCabe CS, Haigh RC, Shenker NG, Lewis JS, Blake DR (2004) Phantoms in Rheumatology. In Osteoarthritic Joint Pain (Novartis Foundation), pp 154–178.

  • McCabe C, Grieve S, Harris N (2011) Electrical sensory discrimination therapy in Complex Regional Pain Syndrome (CRPS). Eur J Pain Suppl 5(1):136

    Article  Google Scholar 

  • Moseley GL (2004) Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial. Pain 108:192–198

    Google Scholar 

  • Moseley GL (2005) Distorted body image in complex regional pain syndrome. Neurology 65:773

    Article  PubMed  Google Scholar 

  • Munts AG, Mugge W, Meurs TS, Schouten AC, Marinus J, Moseley GL, Van der Helm FCT, Van Hilten JJ (2011) Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modelling Approach. BMC Neurol 11:53

    Article  PubMed  Google Scholar 

  • Oaklander AL, Fields HL (2009) Is reflex sympathetic dystrophy/CRPS type 1 a small-fibre neuropathy? Ann Neurol 65:629–638

    Article  PubMed  Google Scholar 

  • Ozgül A, Vural D, Taşkaynatanş MA (2011) Blocking of TNF-α in Complex Regional Pain Syndrome: a case of reflex sympathetic dystrophy resolved with Etanercept in a patient with ankylosing spondylitis. Turk J Rheumatol 26(3):239–242

    Article  Google Scholar 

  • Picarelli H, Teixera MJ, Ciampi de Andrade D, Myczkowski L, Luvisotto TB, Yeng LT, Fonoff ET, Pridmore S, Marcolini MA (2010) Repetitive transcranial magnetic stimulation as an add-on to pharmacological therapy in CRPS type 1. J Pain 11(11):1203–1210

    Article  PubMed  Google Scholar 

  • Peltz E, Seifert F, Lanz S, Muller R, Maihofner C (2011) Impaired hand size estimation in CRPS. J Pain 12:1095–1101

    Article  PubMed  Google Scholar 

  • Pleger B, Ragert P, Schwenkreis P, Forster AF, Wilimzig C, Dinse H, Nicolas V, Maier C, Tegenthoff M (2006) Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome. NeuroImage 32:503–510

    Article  PubMed  Google Scholar 

  • Pleger B, Tegenthoff M, Ragert P, Forster AF, Dinese HR, Schwenkreis P, Nicolas V, Maier C (2005) Sensorimotor retuning in complex regional pain syndrome parallels pain reduction. Ann Neurol 57:609

    Article  Google Scholar 

  • Preston C, Newport R (2011) Analgesic effects of multisensory illusions in osteoarthritis. Rheumatology online

  • Ramachandran VS, Altschuler EL (2009) The use of visual feedback, in particular mirror visual feedback, in restoring brain function. Brain 132:1693–1710

    Article  PubMed  CAS  Google Scholar 

  • Rather LJ (1971) Disturbance of function (functio laesa): the legendary fifth cardinal sign of inflammation, added by Galen to the four cardinal signs of Celsus. Acad Med 47(3):303–22

    CAS  Google Scholar 

  • Robinson G, Cohen H, Goebel A (2011) A case of Complex Regional Pain Syndrome with agnosia for object orientation. Pain 152 (7):1674–1681

    Article  PubMed  Google Scholar 

  • Rodham K (2009). Adapting to life with complex regional pain syndrome. Royal National Hospital for Rheumatic Diseases Foundation NHS Trust. http://staff.bath.ac.uk/psskr/patient%20leaflet%20version%201.pdf. Accessed 16th January 2012

  • Rommel O, Gehling M, Dertwinkel R et al (1999) Hemisensory impairment in patients with complex regional pain syndrome. Pain 80:95–101

    Article  PubMed  CAS  Google Scholar 

  • Schmid A, Hummel F, Birbaumer N (2011) Pain reduction in a CRPS patient due to tDCS and sensorimotor training: A single case study. Clin Neurophysiol 122(3):S144

    Article  Google Scholar 

  • Schoth F, Waberski TD, Krings T, Gobbele R, Buchner H (2007) Cerebral processing of spontaneous reversals of the rotating Necker cube. Neuroreport 18(13):1335–1338

    Article  PubMed  Google Scholar 

  • Schürmann M, Gradl G, Andress HJ, Furst H, Schildberg FW (1999) Assessment of peripheral sympathetic nervous function for diagnosing early post-traumatic complex regional pain syndrome type I. Pain 80:149–159

    Article  PubMed  Google Scholar 

  • Schürmann M, Gradl G, Zaspel J, Kayser M, Lohr P, Andress HJ (2000) Peripheral sympathetic function as a predictor of complex regional pain syndrome type I (CRPS I) in patients with radial fracture. Auton Neurosci 86:127–134

    Article  PubMed  Google Scholar 

  • Schwoebel J, Friedman R, Duda N, Coslett H (2001) Pain and the body schema; evidence for peripheral effects on mental representations of movement. Brain 124:2098–2104

    Article  PubMed  CAS  Google Scholar 

  • Shiraishi S, Kobayashi H, Nihashi T, Kato K, Iwano S, Nishino M, Ishigaki T, Ikeda M, Kato T, Ito K, Kimura T (2006) Cerebral glucose metabolism change in patients with complex regional pain syndrome: a PET study. Radiat Med 24:335–344

    Article  PubMed  Google Scholar 

  • Siberceva U, Knotkova H, Fedman D, Cruciani R, Stock V (2009) J Pain 10(4):S39

    Google Scholar 

  • Sime A (2004) Case study of trigeminal neuralgia using neurofeedback and peripheral biofeedback. J Neurother 8:59–71

    Article  Google Scholar 

  • Tracey I, Mantyh PW (2007) The Cerebral Signature for Pain Perception and its Modulation. Neuron 55(3):377–391

    Article  PubMed  CAS  Google Scholar 

  • Turner-Stokes L, Goebel A (2011) Guideline development group: Complex regional pain syndrome in adults- concise guidance. Clin Med J Roy Coll Phys 11(6):596–600

    Google Scholar 

  • Van Hilten JJ, Blumberg H, Schwartzman RJ (2005) Factor IV: movement disorders and dystrophy-pathophysiology and measurement. In: Wilson PR, Stanton-Hicks M, Harden RN (eds) CRPS: Current diagnosis and therapy. IASP Press, Seattle, pp 119–137

    Google Scholar 

  • Van Rijn MA, Van Hilten JJ, Van Dijk JG (2009) Spatiotemporal integration of sensory stimuli in complex regional pain syndrome and dystonia. J Neural Transm 116:559–565

    Article  PubMed  Google Scholar 

  • Van Rijn MA, Marinus J, Putter H, Bosselaar SR, Moseley GL, Van Hilten JJ (2011) Spreading of complex regional pain syndrome: not a random process. J Neural Transm 118(9):1301–1309

    Article  PubMed  Google Scholar 

  • Vartiainen NV, Kirveskari E, Forss N (2008) Central processing of tactile and nociceptive stimuli in complex regional pain syndrome. Clin Neurophysiol 119:2380–2388

    Article  PubMed  Google Scholar 

  • Veldman PJHM, Reynen HM, Arntz IE, Goris RJA (1993) Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 342(8878):1012–1016

    Article  PubMed  CAS  Google Scholar 

  • Wasaka T, Kakig R (2012) Conflict caused by visual feedback modulates activation in somatosensory areas during movement execution. NeuroImage 59:1501–1507

    Article  PubMed  Google Scholar 

  • Wasner G, Heckmann K, Maier C, Baron R (1999) Vascular abnormalities in acute reflex sympathetic dystrophy (CRPS I): complete inhibition of sympathetic nerve activity with recovery. Arch Neurol 56:613–20

    Article  PubMed  CAS  Google Scholar 

  • Wesseldijik F, Huygen FJ, Hejmans-Antonissen C, Niehof SP, Zijistra FJ (2008) Tumour necrosis factor-alpha and interleukin-6 are not correlated with the characteristics of Complex Regional pain Syndrome type 1 in 66 patients. Eur J Pain 12(6):716–721

    Article  Google Scholar 

  • Wu CT, Fan YM, Sun CM, Cecil B, Yeh CC, Yang CP, Wang CS (2006) Correlation between changes in regional cerebral blood flow and pain relief in CRPS 1. Clin Nuclear Med 31(6):317–320

    Google Scholar 

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The authors also wish to thank the reviewers for their helpful comments.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Bath Centre for Pain Services, The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath, BA1 1RL, UK

    Jacqueline Bailey, Sara Nelson, Jenny Lewis & Candida S. McCabe

  2. The Faculty of Health and Life Sciences, University of the West of England, Bristol, UK

    Jacqueline Bailey, Sara Nelson & Candida S. McCabe

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  1. Jacqueline Bailey
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  2. Sara Nelson
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  4. Candida S. McCabe
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Correspondence to Candida S. McCabe.

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Bailey, J., Nelson, S., Lewis, J. et al. Imaging and Clinical Evidence of Sensorimotor Problems in CRPS: Utilizing Novel Treatment Approaches. J Neuroimmune Pharmacol 8, 564–575 (2013). https://doi.org/10.1007/s11481-012-9405-9

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