Funktionelle Bildgebung bei neuropathischen Schmerzen

E. Peltz; S. Ott; F. Seifert; C. Maihöfner

doi:10.1055/s-0038-1628271

Nervenheilkunde, Table of Contents

Nervenheilkunde 2012; 31(03): 132-139
DOI: 10.1055/s-0038-1628271

Schmerz

Schattauer GmbH

Funktionelle Bildgebung bei neuropathischen Schmerzen

Functional imaging of neuropathic pain

Authors

E. Peltz

¹Neurologische Klinik der Universität Erlangen-Nürnberg
S. Ott

¹Neurologische Klinik der Universität Erlangen-Nürnberg
F. Seifert

¹Neurologische Klinik der Universität Erlangen-Nürnberg
C. Maihöfner

¹Neurologische Klinik der Universität Erlangen-Nürnberg

Abstract

Zusammenfassung

Patienten mit neuropathischen Schmerzen zeigen eine heterogene klinische Manifestation mit spontanen und stimulusevozierbaren Schmerzen. In den vergangenen Jahren ge-lang es, detaillierte Einblicke in die Verarbeitung von neuropathischen Schmerzen im menschlichen Gehirn zu gewinnen. Mittels funktionell-bildgebenden Methoden konnten veränderte Aktivitätsmuster in zentralen schmerzverarbeitenden Netzwerken detektiert werden. Des Weiteren fanden sich kortikale Reorganisationsphänomene mit Verschiebungen im Bereich somatotopisch gegliederter Hirnareale des somatosensorischen und motorischen Systems. Der Nachweis neuroplastischer Veränderungen gelang nicht nur auf funktioneller Ebene, auch die strukturelle und neuronal-chemische Konstitution des Gehirns scheint bei chronischen Schmerzen beeinflusst zu sein. Im Zuge einer erfolgreichen Therapie zeigten sich die zentralen reorganisatorischen Vorgänge rückläufig. Eine Implementierung dieser Erkenntnisse in zukünftige neurorehabilitative Strategien erscheint denkbar.

Summary

Patients suffering from neuropathic pain frequently present with a puzzling clinical picture including spontaneous and evoked pain. During the last years detailed insights were gained into the processing of neuropathic pain in the human brain. Studies using functional neuroimaging techniques provided evidence for activity changes in central nociceptive networks and additional central reorganization phenomena in the central somatosensory and motor system. Moreover, it has been shown that chronic neuropathic pain influences the structural and neurochemical configuration of the brain. Future neurorehabilitation strategies may benefit from these findings.

Schlüsselwörter

Neuropathischer Schmerz - funktionelle Bildgebung - Neuroplastizität - kortikale Reorganisation

Keywords

Neuropathic pain - functional imaging - neuronal plasticity - cortical reorganization

Full Text

References

Literatur
1 McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain 2006; 10 (Suppl. 02) 127-35.
2 Baron R. Mechanisms of disease: neuropathic pain – a clinical perspective. Nat Clin Pract Neurol 2006; 2 (Suppl. 02) 95-106.
3 Stanton-Hicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain 1995; 63 (Suppl. 01) 127-33.
4 Tolle TR, Baron R. [Neuropathic pain. Basic principles for successful therapy]. MMW Fortschr Med 2002; 144 (21) 41-4.
5 Tecchio F, Padua L, Aprile I, Rossini PM. Carpal tunnel syndrome modifies sensory hand cortical somatotopy: a MEG study. Hum Brain Mapp 2002; 17 (Suppl. 01) 28-36.
6 Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353 9168 1959-64.
7 Gustin SM, Wrigley PJ, Henderson LA, Siddall PJ. Brain circuitry underlying pain in response to imagined movement in people with spinal cord injury. Pain 2010; 148 (Suppl. 03) 438-45.
8 Melzack R. From the gate to the neuromatrix. Pain 1999; Suppl 6: 121-6.
9 Melzack R. Pain and the neuromatrix in the brain. J Dent Educ 2001; 65 (12) 1378-82.
10 Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron 2007; 55 (Suppl. 03) 377-91.
11 Lanz S, Seifert F, Maihofner C. Brain activity associated with pain, hyperalgesia and allodynia: an ALE meta-analysis. J Neural Transm. 2011 Mar 4, E-pub ahead of print.
12 Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending control of nociception: Specificity, recruitment and plasticity. Brain Res Rev 2009; 60 (Suppl. 01) 214-25.
13 May A. Neuroimaging: visualising the brain in pain. Neurol Sci 2007; 28 Suppl 2: S101-7.
14 Treede RD, Kenshalo DR, Gracely RH, Jones AK. The cortical representation of pain. Pain 1999; 79 2–3 105-11.
15 Di Piero V, Jones AK, Iannotti F, Powell M, Perani D, Lenzi GL. et al. Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain 1991; 46 (Suppl. 01) 9-12.
16 Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M. Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain 1995; 63 (Suppl. 02) 225-36.
17 Iadarola MJ, Max MB, Berman KF, Byas-Smith MG, Coghill RC, Gracely RH. et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain 1995; 63 (Suppl. 01) 55-64.
18 Moisset X, Bouhassira D. Brain imaging of neuropathic pain. Neuroimage 2007; 37 Suppl 1: S80-8.
19 Freynhagen R, Rolke R, Baron R, Tolle TR, Rutjes AK, Schu S. et al. Pseudoradicular and radicular low-back pain – a disease continuum rather than different entities? Answers from quantitative sensory testing. Pain 2008; 135 1–2 65-74.
20 Baliki MN, Chialvo DR, Geha PY, Levy RM, Harden RN, Parrish TB. et al. Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. J Neurosci 2006; 26 (47) 12165-73.
21 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 (Suppl. 04) 463-84.
22 Borsook D, Moulton EA, Schmidt KF, Becerra LR. Neuroimaging revolutionizes therapeutic approaches to chronic pain. Mol Pain 2007; 3: 25.
23 Baron R, Baron Y, Disbrow E, Roberts TP. Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study. Neurology 1999; 53 (Suppl. 03) 548-57.
24 Lorenz J, Cross DJ, Minoshima S, Morrow TJ, Paulson PE, Casey KL. A unique representation of heat allodynia in the human brain. Neuron 2002; 35 (Suppl. 02) 383-93.
25 Maihofner C, Forster C, Birklein F, Neundorfer B, Handwerker HO. Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study. Pain 2005; 114 1–2 93-103.
26 Zambreanu L, Wise RG, Brooks JC, Iannetti GD, Tracey I. A role for the brainstem in central sensitisation in humans. Evidence from functional magnetic resonance imaging. Pain 2005; 114 (Suppl. 03) 397-407.
27 Seifert F, Maihofner C. Representation of cold allodynia in the human brain – a functional MRI study. Neuroimage 2007; 35 (Suppl. 03) 1168-80.
28 Seifert F, Jungfer I, Schmelz M, Maihofner C. Representation of UV-B-induced thermal and mechanical hyperalgesia in the human brain: a functional MRI study. Hum Brain Mapp 2008; 29 (12) 1327-42.
29 Seifert F, Bschorer K, De Col R, Filitz J, Peltz E, Koppert W. et al. Medial prefrontal cortex activity is predictive for hyperalgesia and pharmacological antihyperalgesia. J Neurosci 2009; 29 (19) 6167-75.
30 Ducreux D, Attal N, Parker F, Bouhassira D. Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain 2006; 129 Pt 4 963-76.
31 Becerra L, Morris S, Bazes S, Gostic R, Sherman S, Gostic J. et al. Trigeminal neuropathic pain alters responses in CNS circuits to mechanical (brush) and thermal (cold and heat) stimuli. J Neurosci 2006; 26 (42) 10646-57.
32 Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N. et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 1995; 375 6531 482-4.
33 Elbert T, Flor H, Birbaumer N, Knecht S, Hampson S, Larbig W. et al. Extensive reorganization of the somatosensory cortex in adult humans after nervous system injury. Neuroreport 1994; 5 (18) 2593-7.
34 Yang TT, Gallen CC, Ramachandran VS, Cobb S, Schwartz BJ, Bloom FE. Noninvasive detection of cerebral plasticity in adult human somatosensory cortex. Neuroreport 1994; 5 (Suppl. 06) 701-4.
35 Lotze M, Grodd W, Birbaumer N, Erb M, Huse E, Flor H. Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain?. Nat Neurosci 1999; 2 (Suppl. 06) 501-2.
36 Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Patterns of cortical reorganization in complex regional pain syndrome. Neurology 2003; 61 (12) 1707-15.
37 Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Cortical reorganization during recovery from complex regional pain syndrome. Neurology 2004; 63 (Suppl. 04) 693-701.
38 Maihofner C, Baron R, DeCol R, Binder A, Birklein F, Deuschl G. et al. The motor system shows adaptive changes in complex regional pain syndrome. Brain 2007; 130 Pt 10 2671-87.
39 Vartiainen NV, Kirveskari E, Forss N. Central processing of tactile and nociceptive stimuli in complex regional pain syndrome. Clin Neurophysiol 2008; 119 (10) 2380-8.
40 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 (Suppl. 06) 1398-403.
41 Cauda F, Sacco K, Duca S, Cocito D, D’Agata F, Geminiani GC. et al. Altered resting state in diabetic neuropathic pain. PLoS One 2009; 4 (Suppl. 02) e4542.
42 Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA 2001; 98 (Suppl. 02) 676-82.
43 Cauda F, D‘Agata F, Sacco K, Duca S, Cocito D, Paolasso I. et al. Altered resting state attentional networks in diabetic neuropathic pain. J Neurol Neurosurg Psychiatry 2010; 81 (Suppl. 07) 806-11.
44 Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ. et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science 2004; 303 5661 1162-7.
45 Lorenz J, Minoshima S, Casey KL. Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation. Brain 2003; 126 Pt 5 1079-91.
46 Oertel BG, Preibisch C, Wallenhorst T, Hummel T, Geisslinger G, Lanfermann H. et al. Differential opioid action on sensory and affective cerebral pain processing. Clin Pharmacol Ther 2008; 83 (Suppl. 04) 577-88.
47 Petrovic P, Kalso E, Petersson KM, Ingvar M. Placebo and opioid analgesia – imaging a shared neuronal network. Science 2002; 295 5560 1737-40.
48 Price DD, Craggs J, Verne GN, Perlstein WM, Robinson ME. Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain 2007; 127 1–2 63-72.
49 Rainville P, Duncan GH. Functional brain imaging of placebo analgesia: methodological challenges and recommendations. Pain 2006; 121 (Suppl. 03) 177-80.
50 Derbyshire SW, Vogt BA, Jones AK. Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex. Exp Brain Res 1998; 118 (Suppl. 01) 52-60.
51 Frankenstein UN, Richter W, McIntyre MC, Remy F. Distraction modulates anterior cingulate gyrus activations during the cold pressor test. Neuroimage 2001; 14 (Suppl. 04) 827-36.
52 Petrovic P, Petersson KM, Ghatan PH, Stone-Elander S, Ingvar M. Pain-related cerebral activation is altered by a distracting cognitive task. Pain 2000; 85 1–2 19-30.
53 Derbyshire SW, Whalley MG, Stenger VA, Oakley DA. Cerebral activation during hypnotically induced and imagined pain. Neuroimage 2004; 23 (Suppl. 01) 392-401.
54 Faymonville ME, Boly M, Laureys S. Functional neuroanatomy of the hypnotic state. J Physiol Paris 2006; 99 4-6 463-9.
55 Faymonville ME, Roediger L, Del Fiore G, Delgueldre C, Phillips C, Lamy M. et al. Increased cerebral functional connectivity underlying the anti-nociceptive effects of hypnosis. Brain Res Cogn Brain Res 2003; 17 (Suppl. 02) 255-62.
56 Bingel U, Schoell E, Herken W, Buchel C, May A. Habituation to painful stimulation involves the antinociceptive system. Pain 2007; 131 1–2 21-30.
57 Rennefeld C, Wiech K, Schoell ED, Lorenz J, Bingel U. Habituation to pain: further support for a central component. Pain 2010; 148 (Suppl. 03) 503-8.
58 Bingel U, Herken W, Teutsch S, May A. Habituation to painful stimulation involves the antinociceptive system – a 1-year follow-up of 10 participants. Pain 2008; 140 (Suppl. 02) 393-4.
59 Bingel U, Tracey I. Imaging CNS modulation of pain in humans. Physiology (Bethesda) 2008; 23: 371-80.
60 Geha PY, Baliki MN, Harden RN, Bauer WR, Parrish TB, Apkarian AV. The brain in chronic CRPS pain: abnormal gray-white matter interactions in emotional and autonomic regions. Neuron 2008; 60 (Suppl. 04) 570-81.
61 Draganski B, Moser T, Lummel N, Ganssbauer S, Bogdahn U, Haas F. et al. Decrease of thalamic gray matter following limb amputation. Neuroimage 2006; 31 (Suppl. 03) 951-7.
62 Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB. et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci 2004; 24 (46) 10410-5.
63 Schmidt-Wilcke T, Leinisch E, Ganssbauer S, Drag-anski B, Bogdahn U, Altmeppen J. et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain 2006; 125 1–2 89-97.
64 Schmidt-Wilcke T, Luerding R, Weigand T, Jurgens T, Schuierer G, Leinisch E. et al. Striatal grey matter increase in patients suffering from fibromyalgia – a voxel-based morphometry study. Pain 2007; 132 Suppl 1: S109-16.
65 Kuchinad A, Schweinhardt P, Seminowicz DA, Wood PB, Chizh BA, Bushnell MC. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci 2007; 27 (15) 4004-7.
66 Fukui S, Matsuno M, Inubushi T, Nosaka S. N-Acetylaspartate concentrations in the thalami of neuropathic pain patients and healthy comparison subjects measured with (1)H-MRS. Magn Reson Imaging 2006; 24 (Suppl. 01) 75-9.
67 Pattany PM, Yezierski RP, Widerstrom-Noga EG, Bowen BC, Martinez-Arizala A, Garcia BR. et al. Proton magnetic resonance spectroscopy of the thalamus in patients with chronic neuropathic pain after spinal cord injury. Am J Neuroradiol 2002; 23 (Suppl. 06) 901-5.
68 Sorensen L, Siddall PJ, Trenell MI, Yue DK. Differences in metabolites in pain-processing brain regions in patients with diabetes and painful neuropathy. Diabetes Care 2008; 31 (Suppl. 05) 980-1.
69 Stanwell P, Siddall P, Keshava N, Cocuzzo D, Ramadan S, Lin A. et al. Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain. Neuroimage 2010; 53 (Suppl. 02) 544-52.
70 Grachev ID, Fredrickson BE, Apkarian AV. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study. Pain 2000; 89 (Suppl. 01) 7-18.
71 Sprenger T, Henriksen G, Valet M, Platzer S, Berthele A, Tolle TR. [Positron emission tomography in pain research. From the structure to the activity of the opiate receptor system]. Schmerz 2007; 21 (Suppl. 06) 503-13.
72 Chen FY, Tao W, Li YJ. Advances in brain imaging of neuropathic pain. Chin Med J (Engl) 2008; 121 (Suppl. 07) 653-7.
73 Jones AK, Watabe H, Cunningham VJ, Jones T. Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET. Eur J Pain 2004; 8 (Suppl. 05) 479-85.
74 Willoch F, Schindler F, Wester HJ, Empl M, Straube A, Schwaiger M. et al. Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study. Pain 2004; 108 (Suppl. 03) 213-20.
75 Jones AK, Kitchen ND, Watabe H, Cunningham VJ, Jones T, Luthra SK. et al. Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using [11C] diprenorphine and positron emission tomography. J Cereb Blood Flow Metab 1999; 19 (Suppl. 07) 803-8.
76 Willoch F, Tolle TR, Wester HJ, Munz F, Petzold A, Schwaiger M. et al. Central pain after pontine infarction is associated with changes in opioid receptor binding: a PET study with 11C-diprenorphine. AJNR Am J Neuroradiol 1999; 20 (Suppl. 04) 686-90.
77 Kishima H, Saitoh Y, Oshino S, Hosomi K, Ali M, Maruo T. et al. Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H(2)15O PET study. Neuroimage 2010; 49 (Suppl. 03) 2564-9.
78 Maarrawi J, Peyron R, Mertens P, Costes N, Magnin M, Sindou M. et al. Motor cortex stimulation for pain control induces changes in the endogenous opioid system. Neurology 2007; 69 (Suppl. 09) 827-34.
79 Petrovic P. et al. A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy. Pain 1999; 83 (39) 459-70.
80 Peyron R. et al. Allodynia after lateral-medullary (Wallenberg) infarct. A PET study. Brain 1998; 121 PT2 345-56.
81 Witting N. et al. A PET activation study of brush-evokaded allodynia in patients with nerve injury pain. Pain 2006; 120 1-2 145-54.
82 Schweinhardt P. et al. An fMRI study of cerebral processing of brush-evokaded allodynia in neuropathic pain patients. Neuroimage 2006; 32 (19) 256-65.
83 Maihöffer C. et al. Functional imaging of allodynia in complex regional pain patients. Neurology 2006; 66 (Suppl. 05) 711-7.
84 Lebel A. et al. fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children. Brain 2007; 8 131 Pt7 1854-79.
85 Peyron R. et al. An fMRI study of cotical representation of mechanical allodynia in patients with neuropathic pain. Neurology 2004; 63 (10) 1838-46.