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Human cerebellar responses to brush and heat stimuli in healthy and neuropathic pain subjects

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Abstract

Though human pain imaging studies almost always demonstrate activation in the cerebellum, the role of the cerebellum in pain function is not well understood. Here we present results from two studies on the effects of noxious thermal heat and brush applied to the right side of the face in a group of healthy subjects (Group I) and a group of patients with neuropathic pain (Group II) who are more sensitive to both thermal and mechanical stimuli. Statistically significant activations and volumes of activations were defined in the cerebellum. Activated cerebellar structures were identified by colocalization of fMRI activation with the ‘MRI Atlas of the Human Cerebellum’. Functional data (obtained using a 3T magnet) were defined in terms of maximum voxels and volume of activation in the cerebellum. Volume maps were then mapped onto two millimeter serial slices taken through the cerebellum in order to identify activation within regions defined by the activation volume. The data indicate that different regions of the cerebellum are involved in acute and chronic pain processing. Heat produces greater contralateral activation compared with brush, while brush resulted in more ipsilateral/bilateral cerebellar activation. Further, innocuous brush stimuli in healthy subjects produced decreased cerebellar activation in lobules concerned with somatosensory processing. The data also suggest a dichotomy of innocuous stimuli/sensorimotor cerebellum activation versus noxious experience/cognitive/limbic cerebellum activation. These results lead us to propose that the cerebellum may modulate the emotional and cognitive experience that distinguishes the perception of pain from the appreciation of innocuous sensory stimulation.

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References

  1. Ito M. Cerebellar circuitry as a neuronal machine. Prog Neurobiol. 2006;78:272–303.

    Article  PubMed  Google Scholar 

  2. Schmahmann JD. An emerging concept. The cerebellar contribution to higher function. Arch Neurol. 1991;48:1178–87.

    PubMed  CAS  Google Scholar 

  3. Schmahmann JD. Rediscovery of an early concept. Int Rev Neurobiol. 1997;41:3–27.

    Article  PubMed  CAS  Google Scholar 

  4. Saab CY, Willis WD. The cerebellum: organization, functions and its role in nociception. Brain Res Brain Res Rev. 2003;42:85–95.

    Article  PubMed  Google Scholar 

  5. Chambers WW, Sprague JM. Functional localization in the cerebellum. II. Somatotopic organization in cortex and nuclei. AMA Arch Neurol Psychiatry. 1955;74:653–80.

    PubMed  CAS  Google Scholar 

  6. Leiner HC, Leiner AL, Dow RS. Does the cerebellum contribute to mental skills? Behav Neurosci. 1986;100:443–54.

    Article  PubMed  CAS  Google Scholar 

  7. Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. Int Rev Neurobiol. 1997;41:433–40.

    Article  PubMed  CAS  Google Scholar 

  8. Haines DE, Dietrichs E. An HRP study of hypothalamocerebellar and cerebello-hypothalamic connections in squirrel monkey (Saimiri sciureus). J Comp Neurol. 1984;229:559–75.

    Article  PubMed  CAS  Google Scholar 

  9. Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain. 2000;123(Pt 5):1041–50.

    Article  PubMed  Google Scholar 

  10. Schutter DJ, van Honk J. The cerebellum on the rise in human emotion. Cerebellum. 2005;4:290–4.

    Article  PubMed  Google Scholar 

  11. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–84.

    Article  PubMed  Google Scholar 

  12. Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin. 2000;30:263–88.

    Article  PubMed  CAS  Google Scholar 

  13. Helmchen C, Mohr C, Erdmann C, Binkofski F. Cerebellar neural responses related to actively and passively applied noxious thermal stimulation in human subjects: a parametric fMRI study. Neurosci Lett. 2004;361:237–40.

    Article  PubMed  CAS  Google Scholar 

  14. 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;26:10646–57.

    Article  PubMed  CAS  Google Scholar 

  15. Schmahmann JD, Doyon J, Toga AW, Petrides M, Evans AC. MRI atlas of the human cerebellum. San Diego: Academic Press, 2000.

    Google Scholar 

  16. Landgrebe M, Langguth B, Barta W, Hajak G, Eichhammer P. [Modulation of cold-/warm-sensation by cerebellar repetitive transcranial magnetic stimulation (rTMS).]. Psychiatr Prax. 2007;34(1 Suppl.):10–12.

    Article  Google Scholar 

  17. Jackson PL, Meltzoff AN, Decety J. How do we perceive the pain of others? A window into the neural processes involved in empathy. Neuroimage. 2005;24:771–9.

    Article  PubMed  Google Scholar 

  18. Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD. Empathy for pain involves the affective but not sensory components of pain. Science. 2004;303(5661):1157–62.

    Article  PubMed  CAS  Google Scholar 

  19. Restuccia D, Marca GD, Valeriani M, Leggio MG, Molinari M. Cerebellar damage impairs detection of somatosensory input changes. A somatosensory mismatch-negativity study. Brain. 2007;130(Pt 1):276–87.

    PubMed  Google Scholar 

  20. Hartmann MJ, Bower JM. Tactile responses in the granule cell layer of cerebellar folium crus IIa of freely behaving rats. J Neurosci. 2001;21:3549–63.

    PubMed  CAS  Google Scholar 

  21. Holtzman T, Rajapaksa T, Mostofi A, Edgley SA. Different responses of rat cerebellar Purkinje cells and Golgi cells evoked by widespread convergent sensory inputs. J Physiol. 2006;574(Pt 2):491–507.

    Article  PubMed  CAS  Google Scholar 

  22. Saab CY, Willis WD. Nociceptive visceral stimulation modulates the activity of cerebellar Purkinje cells. Exp Brain Res. 2001;140:122–6.

    Article  PubMed  CAS  Google Scholar 

  23. Bukowska D, Mierzejewska-Krzyzowska B, Zguczynski L. Topography and axonal collaterals of trigeminocerebellar projection to the paramedian lobule and uvula in the rabbit cerebellum. Acta Neurobiol Exp (Wars). 2006;66:145–51.

    CAS  Google Scholar 

  24. Patrick GW, Robinson MA. Collateral projections from trigeminal sensory nuclei to ventrobasal thalamus and cerebellar cortex in rats. J Morphol. 1987;192:229–36.

    Article  PubMed  CAS  Google Scholar 

  25. Somana R, Kotchabhakdi N, Walberg F. Cerebellar afferents from the trigeminal sensory nuclei in the cat. Exp Brain Res. 1980;38:57–64.

    Article  PubMed  CAS  Google Scholar 

  26. Steindler DA. Trigeminocerebellar, trigeminotectal, and trigeminothalamic projections: a double retrograde axonal tracing study in the mouse. J Comp Neurol. 1985;237:155–75.

    Article  PubMed  CAS  Google Scholar 

  27. Shumway CA, Morissette J, Gruen P, Bower JM. Plasticity in cerebellar tactile maps in the adult rat. J Comp Neurol. 1999;413:583–92.

    Article  PubMed  CAS  Google Scholar 

  28. Jie W, Pei-Xi C. Discharge response of cerebellar Purkinje cells to stimulation of C-fiber in cat saphenous nerve. Brain Res. 1992;581:269–72.

    Article  PubMed  CAS  Google Scholar 

  29. Heekeren HR, Marrett S, Ruff DA, Bandettini PA, Ungerleider LG. Involvement of human left dorsolateral prefrontal cortex in perceptual decision making is independent of response modality. Proc Natl Acad Sci USA. 2006;103:10023–8.

    Article  PubMed  CAS  Google Scholar 

  30. Molinari M, Leggio MG, Thaut MH. The cerebellum and neural networks for rhythmic sensorimotor synchronization in the human brain. Cerebellum. 2007;6:18–23.

    Article  PubMed  Google Scholar 

  31. Borsook D, Burstein R, Becerra L. Functional imaging of the human trigeminal system: opportunities for new insights into pain processing in health and disease. J Neurobiol. 2004;61:107–25.

    Article  PubMed  Google Scholar 

  32. Moulton E, Pendse G, Morris S, Strassman A, Aiello-Lammens M, Becerra L, et al. Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: an fMRI study. NeuroImage. 2007;35(4):1586–600.

    Article  PubMed  Google Scholar 

  33. Choi JC, Park SK, Kim YH, Shin YW, Kwon JS, Kim JS, et al. Different brain activation patterns to pain and painrelated unpleasantness during the menstrual cycle. Anesthesiology. 2006;105:120–7.

    Article  PubMed  Google Scholar 

  34. DaSilva AF, Becerra L, Makris N, Strassman AM, Gonzalez RG, Geatrakis N, et al. Somatotopic activation in the human trigeminal pain pathway. J Neurosci. 2002;22:8183–92.

    PubMed  CAS  Google Scholar 

  35. de Leeuw R, Davis CE, Albuquerque R, Carlson CR, Andersen AH. Brain activity during stimulation of the trigeminal nerve with noxious heat. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:750–7.

    Article  PubMed  Google Scholar 

  36. Borras MC, Becerra L, Ploghaus A, Gostic JM, DaSilva A, Gonzalez RG, et al. fMRI measurement of CNS responses to naloxone infusion and subsequent mild noxious thermal stimuli in healthy volunteers. J Neurophysiol. 2004;91:2723–33.

    Article  PubMed  CAS  Google Scholar 

  37. Pendse G, Borsook D, Becerra L. A generalized mixture modeling approach applied to the problem of thresholding fMRI statistical maps. Society for Neuroscience. Atlanta, GA; 2006.

  38. Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage. 2003;19:1233–9.

    Article  PubMed  Google Scholar 

  39. Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci. 2004;16:367–78.

    PubMed  Google Scholar 

  40. Woolsey T. Summary of papers on the cerebellum. In: Philip B, editor. Patterns of organization in the central nervous system, 1952. pp 334–6.

  41. Arends JJ, Zeigler HP. Cerebellar connections of the trigeminal system in the pigeon (Columba livia). Brain Res. 1989;487:69–78.

    Article  PubMed  CAS  Google Scholar 

  42. Bukowska D. Trigeminocerebellar projection to the paramedian lobule with emphasis on the climbing fibre zones: a retrograde tracing study in the rabbit. J Hirnforsch. 1996;37:159–72.

    PubMed  CAS  Google Scholar 

  43. Elias SA, Taylor A, Somjen G. Direct and relayed projection of periodontal receptor afferents to the cerebellum in the ferret. Proc R Soc Lond B Biol Sci. 1987;231(1263):199–216.

    PubMed  CAS  Google Scholar 

  44. Falls WM. Direct connections of primary trigeminal afferent axons with trigeminocerebellar projection neurons in the border zone of rat trigeminal nucleus oralis. Neurosci Lett. 1987;83:247–52.

    Article  PubMed  CAS  Google Scholar 

  45. Hayashi H, Sumino R, Sessle BJ. Functional organization of trigeminal subnucleus interpolaris: nociceptive and innocuous afferent inputs, projections to thalamus, cerebellum, and spinal cord, and descending modulation from periaqueductal gray. J Neurophysiol. 1984;51:890–905.

    PubMed  CAS  Google Scholar 

  46. Yatim N, Billig I, Compoint C, Buisseret P, Buisseret-Delmas C. Trigeminocerebellar and trigemino-olivary projections in rats. Neurosci Res. 1996;25:267–83.

    Article  PubMed  CAS  Google Scholar 

  47. Dietrichs E, Walberg F. Cerebellar nuclear afferents – where do they originate? A re-evaluation of the projections from some lower brain stem nuclei. Anat Embryol (Berl). 1987;177:165–72.

    Article  CAS  Google Scholar 

  48. Jacquin MF, Semba K, Rhoades RW, Egger MD. Trigeminal primary afferents project bilaterally to dorsal horn and ipsilaterally to cerebellum, reticular formation, and cuneate, solitary, supratrigeminal and vagal nuclei. Brain Res. 1982;246:285–91.

    Article  PubMed  CAS  Google Scholar 

  49. Saigal RP, Karamanlidis AN, Voogd J, Mangana O, Michaloudi H. Secondary trigeminocerebellar projections in sheep studied with the horseradish peroxidase tracing method. J Comp Neurol. 1980;189:537–53.

    Article  PubMed  CAS  Google Scholar 

  50. Amano N, Hu JW, Sessle BJ. Responses of neurons in feline trigeminal subnucleus caudalis (medullary dorsal horn) to cutaneous, intraoral, and muscle afferent stimuli. J Neurophysiol. 1986;55:227–43.

    PubMed  CAS  Google Scholar 

  51. Sessle BJ, Greenwood LF. Inputs to trigeminal brain stem neurones from facial, oral, tooth pulp and pharyngolaryngeal tissues: I. Responses to innocuous and noxious stimuli. Brain Res. 1976;117:211–26.

    Article  PubMed  CAS  Google Scholar 

  52. Young RF, Perryman KM. Pathways for orofacial pain sensation in the trigeminal brain-stem nuclear complex of the Macaque monkey. J Neurosurg. 1984;61:563–8.

    PubMed  CAS  Google Scholar 

  53. Jacquin MF, Chiaia NL, Klein BG, Rhoades RW. Structurefunction relationships in the rat brainstem subnucleus interpolaris: VI. Cervical convergence in cells deafferented at birth and a potential primary afferent substrate. J Comp Neurol. 1989;283:513–25.

    Article  PubMed  CAS  Google Scholar 

  54. Jacquin MF, Mooney RD, Rhoades RW. Morphology, response properties, and collateral projections of trigeminothalamic neurons in brainstem subnucleus interpolaris of rat. Exp Brain Res. 1986;61:457–68.

    Article  PubMed  CAS  Google Scholar 

  55. Jacquin MF, Renehan WE, Mooney RD, Rhoades RW. Structure-function relationships in rat medullary and cervical dorsal horns. I. Trigeminal primary afferents. J Neurophysiol. 1986;55:1153–86.

    PubMed  CAS  Google Scholar 

  56. Jacquin MF, Rhoades RW. Cell structure and response properties in the trigeminal subnucleus oralis. Somatosens Mot Res. 1990;7:265–88.

    Article  PubMed  CAS  Google Scholar 

  57. Renehan WE, Jacquin MF, Mooney RD, Rhoades RW. Structure-function relationships in rat medullary and cervical dorsal horns. II. Medullary dorsal horn cells. J Neurophysiol. 1986;55:1187–201.

    PubMed  CAS  Google Scholar 

  58. Mori S, Zhang J. Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron. 2006;51:527–39.

    Article  PubMed  CAS  Google Scholar 

  59. Yamada K, Nagakane Y, Yoshikawa K, Kizu O, Ito H, Kubota T, et al. Somatotopic organization of thalamocortical projection fibers as assessed with MR tractography. Radiology. 2007;242:840–5.

    Article  PubMed  Google Scholar 

  60. Helmchen C, Rambold H, Sprenger A, Erdmann C, Binkofski F. Cerebellar activation in opsoclonus: an fMRI study. Neurology. 2003;61:412–5.

    PubMed  CAS  Google Scholar 

  61. Christmann C, Koeppe C, Braus DF, Ruf M, Flor H. A simultaneous EEG-fMRI study of painful electric stimulation. Neuroimage. 2007;34:1428–37.

    Article  PubMed  Google Scholar 

  62. Staud R, Craggs JG, Robinson ME, Perlstein WM, Price DD. Brain activity related to temporal summation of C-fiber evoked pain. Pain. 2007;129(1–2):130–42.

    Article  PubMed  Google Scholar 

  63. Jorntell H, Ekerot CF. Properties of somatosensory synaptic integration in cerebellar granule cells in vivo. J Neurosci. 2006;26:11786–97.

    Article  PubMed  CAS  Google Scholar 

  64. Ekerot CF, Gustavsson P, Oscarsson O, Schouenborg J. Climbing fibres projecting to cat cerebellar anterior lobe activated by cutaneous A and C fibres. J Physiol. 1987;386:529–38.

    PubMed  CAS  Google Scholar 

  65. Ekerot CF, Oscarsson O, Schouenborg J. Stimulation of cat cutaneous nociceptive C fibres causing tonic and synchronous activity in climbing fibres. J Physiol. 1987;386:539–46.

    PubMed  CAS  Google Scholar 

  66. Delgado-Garcia JM. [Structure and function of the cerebellum]. Rev Neurol. 2001;33:635–42.

    PubMed  CAS  Google Scholar 

  67. Harel N, Lee SP, Nagaoka T, Kim DS, Kim SG. Origin of negative blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab. 2002;22:908–17.

    Article  PubMed  Google Scholar 

  68. Stefanovic B, Warnking JM, Pike GB. Hemodynamic and metabolic responses to neuronal inhibition. Neuroimage. 2004;22:771–8.

    Article  PubMed  Google Scholar 

  69. Snider RS. Recent contributions to the anatomy and physiology of the cerebellum. Arch Neurol Psych, 1950. pp 196–219.

  70. Allen G, McColl R, Barnard H, Ringe WK, Fleckenstein J, Cullum CM. Magnetic resonance imaging of cerebellarprefrontal and cerebellar-parietal functional connectivity. Neuroimage. 2005;28:39–48.

    Article  PubMed  Google Scholar 

  71. Braak H, Braak E, Yilmazer D, Bohl J. Functional anatomy of human hippocampal formation and related structures. J Child Neurol. 1996;11:265–75.

    PubMed  CAS  Google Scholar 

  72. Middleton FA, Strick PL. Cerebellar output channels. Int Rev Neurobiol. 1997;41:61–82.

    Article  PubMed  CAS  Google Scholar 

  73. Onat F, Cavdar S. Cerebellar connections: hypothalamus. Cerebellum. 2003;2:263–9.

    Article  PubMed  Google Scholar 

  74. Schmahmann JD, Pandya DN. The cerebrocerebellar system. Int Rev Neurobiol. 1997;41:31–60.

    Article  PubMed  CAS  Google Scholar 

  75. Snider RS, Maiti A. Cerebellar contributions to the Papez circuit. J Neurosci Res. 1976;2:133–46.

    Article  PubMed  CAS  Google Scholar 

  76. Manto MU. On the cerebello-cerebral interactions. Cerebellum. 2006;5:286–8.

    Article  PubMed  Google Scholar 

  77. Liu FY, Qiao JT, Dafny N. Cerebellar stimulation modulates thalamic noxious-evoked responses. Brain Res Bull. 1993;30:529–34.

    Article  PubMed  CAS  Google Scholar 

  78. Saab CY, Willis WD. Cerebellar stimulation modulates the intensity of a visceral nociceptive reflex in the rat. Exp Brain Res. 2002;146:117–21.

    Article  PubMed  CAS  Google Scholar 

  79. Dey PK, Ray AK. Anterior cerebellum as a site for morphine analgesia and post-stimulation analgesia. Indian J Physiol Pharmacol. 1982;26:3–12.

    PubMed  CAS  Google Scholar 

  80. Peters M, Bleek C, Monjan AA. Reaction to electrical shock after cerebellar lesions in the rat. Physiol Behav. 1973;10:429–33.

    Article  PubMed  CAS  Google Scholar 

  81. Iwata NK, Ugawa Y. The effects of cerebellar stimulation on the motor cortical excitability in neurological disorders: a review. Cerebellum. 2005;4:218–23.

    Article  PubMed  Google Scholar 

  82. Lu CL, Wu YT, Yeh TC, Chen LF, Chang FY, Lee SD, et al. Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI study. Neurogastroenterol Motil. 2004;16:575–87.

    Article  PubMed  Google Scholar 

  83. Gracely RH, Geisser ME, Giesecke T, Grant MA, Petzke F, Williams DA, et al. Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain. 2004;127(Pt 4):835–43.

    Article  PubMed  CAS  Google Scholar 

  84. Ogino Y, Nemoto H, Inui K, Saito S, Kakigi R, Goto F. Inner experience of pain: imagination of pain while viewing images showing painful events forms subjective pain representation in human brain. Cereb Cortex. 2007;17(5):1139–46.

    Article  PubMed  Google Scholar 

  85. Keltner JR, Furst A, Fan C, Redfern R, Inglis B, Fields HL. Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. J Neurosci. 2006;26:4437–43.

    Article  PubMed  CAS  Google Scholar 

  86. Yoo SS, Teh EK, Blinder RA, Jolesz FA. Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study. Neuroimage. 2004;22:932–40.

    Article  PubMed  Google Scholar 

  87. Ito M. Bases and implications of learning in the cerebellum – adaptive control and internal model mechanism. Prog Brain Res. 2005;148:95–109.

    Article  PubMed  Google Scholar 

  88. Johansen JP, Fields HL. Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal. Nat Neurosci. 2004;7:398–403.

    Article  PubMed  CAS  Google Scholar 

  89. Seymour B, O’Doherty JP, Koltzenburg M, Wiech K, Frackowiak R, Friston K, et al. Opponent appetitiveaversive neural processes underlie predictive learning of pain relief. Nat Neurosci. 2005;8:1234–40.

    Article  PubMed  CAS  Google Scholar 

  90. Bower JM. Control of sensory data acquisition. Int Rev Neurobiol. 1997;41:489–513.

    Article  PubMed  CAS  Google Scholar 

  91. Apps R, Garwicz M. Anatomical and physiological foundations of cerebellar information processing. Nat Rev Neurosci. 2005;6:297–311.

    Article  PubMed  CAS  Google Scholar 

  92. Eccles J, Ito M, Szentagothai J. The cerebellum as a neuronal machine. New York: Springer-Verlag, 1967.

    Google Scholar 

  93. Ohyama T, Nores WL, Murphy M, Mauk MD. What the cerebellum computes. Trends Neurosci. 2003;26:222–7.

    Article  PubMed  CAS  Google Scholar 

  94. Tesche CD, Karhu JJ. Anticipatory cerebellar responses during somatosensory omission in man. Hum Brain Mapp. 2000;9:119–42.

    Article  PubMed  CAS  Google Scholar 

  95. Tesche CD, Karhu J. Somatosensory evoked magnetic fields arising from sources in the human cerebellum. Brain Res. 1997;744:23–31.

    Article  PubMed  CAS  Google Scholar 

  96. Ploghaus A, Tracey I, Gati JS, Clare S, Menon RS, Matthews PM, et al. Dissociating pain from its anticipation in the human brain. Science. 1999;284(5422):1979–81.

    Article  PubMed  CAS  Google Scholar 

  97. Restuccia D, Valeriani M, Barba C, Le Pera D, Capecci M, Filippini V, et al. Functional changes of the primary somatosensory cortex in patients with unilateral cerebellar lesions. Brain. 2001;124(Pt 4):757–68.

    Article  PubMed  CAS  Google Scholar 

  98. Basbaum AI. Distinct neurochemical features of acute and persistent pain. Proc Natl Acad Sci USA. 1999;96:7739–43.

    Article  PubMed  CAS  Google Scholar 

  99. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999;353(9168):1959–64.

    Article  PubMed  CAS  Google Scholar 

  100. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288(5472):1765–9.

    Article  PubMed  CAS  Google Scholar 

  101. Thach WT, Bastian AJ. Role of the cerebellum in the control and adaptation of gait in health and disease. Prog Brain Res. 2004;143:353–66.

    Article  PubMed  Google Scholar 

  102. Bower JM. Is the cerebellum sensory for motor’s sake, or motor for sensory’s sake: the view from the whiskers of a rat? Prog Brain Res. 1997;114:463–96.

    Article  PubMed  CAS  Google Scholar 

  103. Fox PT, Raichle ME, Thach WT. Functional mapping of the human cerebellum with positron emission tomography. Proc Natl Acad Sci USA. 1985;82(21):7462–6.

    Article  PubMed  CAS  Google Scholar 

  104. Kim SG, Ugurbil K, Strick PL. Activation of a cerebellar output nucleus during cognitive processing. Science. 1994;265(5174):949–51.

    Article  PubMed  CAS  Google Scholar 

  105. Hsieh JC, Stahle-Backdahl M, Hagermark O, Stone-Elander S, Rosenquist G, Ingvar M. Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study. Pain. 1996;64:303–14.

    Article  PubMed  CAS  Google Scholar 

  106. Casey KL, Minoshima S, Morrow TJ, Koeppe RA. Comparison of human cerebral activation pattern during cutaneous warmth, heat pain, and deep cold pain. J Neurophysiol. 1996;76:571–81.

    PubMed  CAS  Google Scholar 

  107. Svensson P, Minoshima S, Beydoun A, Morrow TJ, Casey KL. Cerebral processing of acute skin and muscle pain in humans. J Neurophysiol. 1997;78:450–60.

    PubMed  CAS  Google Scholar 

  108. Xu X, Fukuyama H, Yazawa S, Mima T, Hanakawa T, Magata Y, et al. Functional localization of pain perception in the human brain studied by PET. Neuroreport. 1997;8:555–9.

    Article  PubMed  CAS  Google Scholar 

  109. Derbyshire SW, Jones AK. Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography. Pain. 1998;76:127–35.

    Article  PubMed  CAS  Google Scholar 

  110. Iadarola MJ, Berman KF, Zeffiro TA, Byas-Smith MG, Gracely RH, Max MB, et al. Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. Brain. 1998;121(Pt 5):931–47.

    Article  PubMed  Google Scholar 

  111. May A, Kaube H, Buchel C, Eichten C, Rijntjes M, Juptner M, et al. Experimental cranial pain elicited by capsaicin: a PET study. Pain. 1998;74:61–6.

    Article  PubMed  CAS  Google Scholar 

  112. Paulson PE, Minoshima S, Morrow TJ, Casey KL. Gender differences in pain perception and patterns of cerebral activation during noxious heat stimulation in humans. Pain. 1998;76:223–9.

    Article  PubMed  CAS  Google Scholar 

  113. Becerra LR, Breiter HC, Stojanovic M, Fishman S, Edwards A, Comite AR, et al. Human brain activation under controlled thermal stimulation and habituation to noxious heat: an fMRI study. Magn Reson Med. 1999;41:1044–57.

    Article  PubMed  CAS  Google Scholar 

  114. Coghill RC, Sang CN, Maisog JM, Iadarola MJ. Pain intensity processing within the human brain: a bilateral, distributed mechanism. J Neurophysiol. 1999;82:1934–43.

    PubMed  CAS  Google Scholar 

  115. Peyron R, Garcia-Larrea L, Gregoire MC, Costes N, Convers P, Lavenne F, et al. Haemodynamic brain responses to acute pain in humans: sensory and attentional networks. Brain. 1999;122(Pt 9):1765–80.

    Article  PubMed  Google Scholar 

  116. Becerra L, Breiter HC, Wise R, Gonzalez RG, Borsook D. Reward circuitry activation by noxious thermal stimuli. Neuron. 2001;32:927–46.

    Article  PubMed  CAS  Google Scholar 

  117. Casey KL, Morrow TJ, Lorenz J, Minoshima S. Temporal and spatial dynamics of human forebrain activity during heat pain: analysis by positron emission tomography. J Neurophysiol. 2001;85:951–9.

    PubMed  CAS  Google Scholar 

  118. Coghill RC, Gilron I, Iadarola MJ. Hemispheric lateralization of somatosensory processing. J Neurophysiol. 2001;85:2602–12.

    PubMed  CAS  Google Scholar 

  119. Bingel U, Quante M, Knab R, Bromm B, Weiller C, Buchel C. Subcortical structures involved in pain processing: evidence from single-trial fMRI. Pain. 2002;99:313–21.

    Article  PubMed  CAS  Google Scholar 

  120. Derbyshire SW, Jones AK, Creed F, Starz T, Meltzer CC, Townsend DW, et al. Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls. Neuroimage. 2002;16:158–68.

    Article  PubMed  CAS  Google Scholar 

  121. Helmchen C, Mohr C, Erdmann C, Petersen D, Nitschke MF. Differential cerebellar activation related to perceived pain intensity during noxious thermal stimulation in humans: a functional magnetic resonance imaging study. Neurosci Lett. 2003;335:202–6.

    Article  PubMed  CAS  Google Scholar 

  122. Koyama T, McHaffie JG, Laurienti PJ, Coghill RC. The single-epoch fMRI design: validation of a simplified paradigm for the collection of subjective ratings. Neuroimage. 2003;19:976–87.

    Article  PubMed  Google Scholar 

  123. Strigo IA, Duncan GH, Boivin M, Bushnell MC. Differentiation of visceral and cutaneous pain in the human brain. J Neurophysiol. 2003;89:3294–303.

    Article  PubMed  Google Scholar 

  124. Ibinson JW, Small RH, Algaze A, Roberts CJ, Clark DL, Schmalbrock P. Functional magnetic resonance imaging studies of pain: an investigation of signal decay during and across sessions. Anesthesiology. 2004;101:960–9.

    Article  PubMed  Google Scholar 

  125. 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.

    Article  PubMed  CAS  Google Scholar 

  126. Wiech K, Seymour B, Kalisch R, Stephan KE, Koltzenburg M, Driver J, et al. Modulation of pain processing in hyperalgesia by cognitive demand. Neuroimage. 2005;27:59–69.

    Article  PubMed  Google Scholar 

  127. Albuquerque RJ, de Leeuw R, Carlson CR, Okeson JP, Miller CS, Andersen AH. Cerebral activation during thermal stimulation of patients who have burning mouth disorder: an fMRI study. Pain. 2006;122:223–34.

    Article  PubMed  Google Scholar 

  128. Kong J, White NS, Kwong KK, Vangel MG, Rosman IS, Gracely RH, et al. Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity. Hum Brain Mapp. 2006;27:715–21.

    Article  PubMed  Google Scholar 

  129. Seminowicz DA, Davis KD. Interactions of pain intensity and cognitive load: the brain stays on task. Cereb Cortex. 2007;17(6):1412–22.

    Article  PubMed  Google Scholar 

  130. Bantick SJ, Wise RG, Ploghaus A, Clare S, Smith SM, Tracey I. Imaging how attention modulates pain in humans using functional MRI. Brain. 2002;125(Pt 2):310–9.

    Article  PubMed  Google Scholar 

  131. Brooks JC, Nurmikko TJ, Bimson WE, Singh KD, Roberts N. fMRI of thermal pain: effects of stimulus laterality and attention. Neuroimage. 2002;15:293–301.

    Article  PubMed  Google Scholar 

  132. Smith KA, Ploghaus A, Cowen PJ, McCleery JM, Goodwin GM, Smith S, et al. Cerebellar responses during anticipation of noxious stimuli in subjects recovered from depression. Functional magnetic resonance imaging study. Br J Psychiatry. 2002;181:411–5.

    Article  PubMed  CAS  Google Scholar 

  133. Moriguchi Y, Decety J, Ohnishi T, Maeda M, Mori T,Nemoto K, et al. Empathy and judging other’s pain: an fMRI study of alexithymia. Cereb Cortex. 2006 Dec 5;[Epub ahead of print].

  134. 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.

    Article  PubMed  Google Scholar 

  135. Schweinhardt P, Glynn C, Brooks J, McQuay H, Jack T, Chessell I, et al. An fMRI study of cerebral processing of brush-evoked allodynia in neuropathic pain patients. Neuroimage. 2006;32:256–65.

    Article  PubMed  Google Scholar 

  136. Witting N, Kupers RC, Svensson P, Jensen TS. A PET activation study of brush-evoked allodynia in patients with nerve injury pain. Pain. 2006;120:145–54.

    Article  PubMed  Google Scholar 

  137. Geha PY, Baliki MN, Chialvo DR, Harden RN, Paice JA, Apkarian AV. Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain. 2007;128:88–100.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. PAIN Group, Brain Imaging Center, McLean Hospital, Harvard Medical School, Massachusetts, USA

    D. Borsook, E. A. Moulton, S. Tully & L. Becerra

  2. Cerebellar Research Group, Ataxia Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Massachusetts, USA

    J. D. Schmahmann

  3. PAIN Group, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA, USA

    D. Borsook

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  1. D. Borsook
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  2. E. A. Moulton
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  3. S. Tully
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  4. J. D. Schmahmann
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  5. L. Becerra
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Correspondence to D. Borsook.

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Borsook, D., Moulton, E.A., Tully, S. et al. Human cerebellar responses to brush and heat stimuli in healthy and neuropathic pain subjects. Cerebellum 7, 252–272 (2008). https://doi.org/10.1007/s12311-008-0011-6

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