Experimental Brain Research

, Volume 205, Issue 1, pp 1–12 | Cite as

From the neuromatrix to the pain matrix (and back)



Pain is a conscious experience, crucial for survival. To investigate the neural basis of pain perception in humans, a large number of investigators apply noxious stimuli to the body of volunteers while sampling brain activity using different functional neuroimaging techniques. These responses have been shown to originate from an extensive network of brain regions, which has been christened the Pain Matrix and is often considered to represent a unique cerebral signature for pain perception. As a consequence, the Pain Matrix is often used to understand the neural mechanisms of pain in health and disease. Because the interpretation of a great number of experimental studies relies on the assumption that the brain responses elicited by nociceptive stimuli reflect the activity of a cortical network that is at least partially specific for pain, it appears crucial to ascertain whether this notion is supported by unequivocal experimental evidence. Here, we will review the original concept of the “Neuromatrix” as it was initially proposed by Melzack and its subsequent transformation into a pain-specific matrix. Through a critical discussion of the evidence in favor and against this concept of pain specificity, we show that the fraction of the neuronal activity measured using currently available macroscopic functional neuroimaging techniques (e.g., EEG, MEG, fMRI, PET) in response to transient nociceptive stimulation is likely to be largely unspecific for nociception.


Nociception Pain matrix Saliency Multimodal fMRI EEG 


  1. Albe-Fessard D, Berkley KJ, Kruger L, Ralston HJ 3rd, Willis WD Jr (1985) Diencephalic mechanisms of pain sensation. Brain Res 356:217–296PubMedGoogle Scholar
  2. Andersson SA, Rydenhag B (1985) Cortical nociceptive systems. Philos Trans R Soc Lond B Biol Sci 308:347–359PubMedGoogle Scholar
  3. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9:463–484PubMedGoogle Scholar
  4. Arendt-Nielsen L (1994) Characteristics, detection, and modulation of laser-evoked vertex potentials. Acta Anaesthesiol Scand Suppl 101:7–44PubMedGoogle Scholar
  5. Avenanti A, Bueti D, Galati G, Aglioti SM (2005) Transcranial magnetic stimulation highlights the sensorimotor side of empathy for pain. Nat Neurosci 8:955–960PubMedGoogle Scholar
  6. Bancaud J, Talairach J, Geier S, Bonis A, Trottier S, Manrique M (1976) Behavioral manifestations induced by electric stimulation of the anterior cingulate gyrus in man. Rev Neurol (Paris) 132:705–724Google Scholar
  7. Beckmann CF, Smith SA (2004) Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Trans Med Imaging 23:137–152PubMedGoogle Scholar
  8. Beydoun A, Morrow TJ, Shen JF, Casey KL (1993) Variability of laser-evoked potentials: attention, arousal and lateralized differences. Electroencephalogr Clin Neurophysiol 88:173–181PubMedGoogle Scholar
  9. Boly M, Faymonville ME, Schnakers C, Peigneux P, Lambermont B, Phillips C, Lancellotti P, Luxen A, Lamy M, Moonen G, Maquet P, Laureys S (2008) Perception of pain in the minimally conscious state with PET activation: an observational study. Lancet Neurol 7:1013–1020PubMedGoogle Scholar
  10. Bornhovd K, Quante M, Glauche V, Bromm B, Weiller C, Buchel C (2002) Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. Brain 125:1326–1336PubMedGoogle Scholar
  11. Bromm B, Treede RD (1987) Human cerebral potentials evoked by CO2 laser stimuli causing pain. Exp Brain Res 67:153–162PubMedGoogle Scholar
  12. Brooks J, Tracey I (2005) From nociception to pain perception: imaging the spinal and supraspinal pathways. J Anat 207:19–33PubMedGoogle Scholar
  13. Buchel C, Bornhovd K, Quante M, Glauche V, Bromm B, Weiller C (2002) Dissociable neural responses related to pain intensity, stimulus intensity, and stimulus awareness within the anterior cingulate cortex: a parametric single-trial laser functional magnetic resonance imaging study. J Neurosci 22:970–976PubMedGoogle Scholar
  14. Budd TW, Michie PT (1994) Facilitation of the N1 peak of the auditory ERP at short stimulus intervals. Neuroreport 5:2513–2516PubMedGoogle Scholar
  15. Bushnell MC, Apkarian AV (2005) Representation of pain in the brain. In: McMahon S, Koltzenburg M (eds) Textbook of pain, 5th edn. Churchill Livingstone, Philadelphia, pp 267–289Google Scholar
  16. Carmon A, Mor J, Goldberg J (1976) Evoked cerebral responses to noxious thermal stimuli in humans. Exp Brain Res 25:103–107PubMedGoogle Scholar
  17. Carmon A, Dotan Y, Sarne Y (1978) Correlation of subjective pain experience with cerebral evoked responses to noxious thermal stimulations. Exp Brain Res 33:445–453PubMedGoogle Scholar
  18. Chapman CR, Chen AC, Colpitts YM, Martin RW (1981a) Sensory decision theory describes evoked potentials in pain discrimination. Psychophysiology 18:114–120PubMedGoogle Scholar
  19. Chapman CR, Colpitts YH, Mayeno JK, Gagliardi GJ (1981b) Rate of stimulus repetition changes evoked potential amplitude: dental and auditory modalities compared. Exp Brain Res 43:246–252PubMedGoogle Scholar
  20. Charlesworth G, Soryal I, Smith S, Sisodiya SM (2009) Acute, localised paroxysmal pain as the initial manifestation of focal seizures: a case report and a brief review of the literature. Pain 141:300–305PubMedGoogle Scholar
  21. Cheng Y, Lin CP, Liu HL, Hsu YY, Lim KE, Hung D, Decety J (2007) Expertise modulates the perception of pain in others. Curr Biol 17:1708–1713PubMedGoogle Scholar
  22. Clark JA, Brown CA, Jones AK, El-Deredy W (2008) Dissociating nociceptive modulation by the duration of pain anticipation from unpredictability in the timing of pain. Clin Neurophysiol 119:2870–2878Google Scholar
  23. Coghill RC, Sang CN, Maisog JM, Iadarola MJ (1999) Pain intensity processing within the human brain: a bilateral, distributed mechanism. J Neurophysiol 82:1934–1943PubMedGoogle Scholar
  24. Corkin S, Hebben N (1981) Subjective estimates of chronic pain before and after psychosurgery or treatment in a pain unit. Pain 1:S150Google Scholar
  25. Craig AD (2003) Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci 26:1–30PubMedGoogle Scholar
  26. Craig AD, Bushnell MC, Zhang ET, Blomqvist A (1994) A thalamic nucleus specific for pain and temperature sensation. Nature 372:770–773PubMedGoogle Scholar
  27. Craig AD, Chen K, Bandy D, Reiman EM (2000) Thermosensory activation of insular cortex. Nat Neurosci 3:184–190PubMedGoogle Scholar
  28. Derbyshire SW, Jones AK, Gyulai F, Clark S, Townsend D, Firestone LL (1997) Pain processing during three levels of noxious stimulation produces differential patterns of central activity. Pain 73:431–445PubMedGoogle Scholar
  29. Descartes R (1649) Les passions de l’âme. L. Elzevir, AmsterdamGoogle Scholar
  30. Dillmann J, Miltner WH, Weiss T (2000) The influence of semantic priming on event-related potentials to painful laser-heat stimuli in humans. Neurosci Lett 284:53–56PubMedGoogle Scholar
  31. Dong WK, Chudler EH, Sugiyama K, Roberts VJ, Hayashi T (1994) Somatosensory, multisensory, and task-related neurons in cortical area 7b (PF) of unanesthetized monkeys. J Neurophysiol 72:542–564PubMedGoogle Scholar
  32. Downar J, Crawley AP, Mikulis DJ, Davis KD (2000) A multimodal cortical network for the detection of changes in the sensory environment. Nat Neurosci 3:277–283PubMedGoogle Scholar
  33. Downar J, Mikulis DJ, Davis KD (2003) Neural correlates of the prolonged salience of painful stimulation. Neuroimage 20:1540–1551PubMedGoogle Scholar
  34. Dum RP, Levinthal DJ, Strick PL (2009) The spinothalamic system targets motor and sensory areas in the cerebral cortex of monkeys. J Neurosci 29:14223–14235PubMedGoogle Scholar
  35. Eisenberger NI, Lieberman MD, Williams KD (2003) Does rejection hurt? An FMRI study of social exclusion. Science 302:290–292PubMedGoogle Scholar
  36. Fecteau JH, Munoz DP (2006) Salience, relevance, and firing: a priority map for target selection. Trends Cogn Sci 10:382–390PubMedGoogle Scholar
  37. Foltz EL, White LE Jr (1962) Pain “relief” by frontal cingulumotomy. J Neurosurg 19:89–100PubMedGoogle Scholar
  38. Foltz EL, White LE (1968) The role of rostral cingulumotomy in “pain” relief. Int J Neurol 6:353–373PubMedGoogle Scholar
  39. Frot M, Magnin M, Mauguiere F, Garcia-Larrea L (2007) Human SII and posterior insula differently encode thermal laser stimuli. Cereb Cortex 17:610–620PubMedGoogle Scholar
  40. Frot M, Mauguiere F, Magnin M, Garcia-Larrea L (2008) Parallel processing of nociceptive A-delta inputs in SII and midcingulate cortex in humans. J Neurosci 28:944–952PubMedGoogle Scholar
  41. Garcia-Larrea L, Peyron R, Laurent B, Mauguiere F (1997) Association and dissociation between laser-evoked potentials and pain perception. Neuroreport 8:3785–3789PubMedGoogle Scholar
  42. Garcia-Larrea L, Convers P, Magnin M, Andre-Obadia N, Peyron R, Laurent B, Mauguiere F (2002) Laser-evoked potential abnormalities in central pain patients: the influence of spontaneous and provoked pain. Brain 125:2766–2781PubMedGoogle Scholar
  43. Garcia-Larrea L, Frot M, Valeriani M (2003) Brain generators of laser-evoked potentials: from dipoles to functional significance. Neurophysiol Clin 33:279–292PubMedGoogle Scholar
  44. Godinho F, Magnin M, Frot M, Perchet C, Garcia-Larrea L (2006) Emotional modulation of pain: is it the sensation or what we recall? J Neurosci 26:11454–11461PubMedGoogle Scholar
  45. Gracely RH, Geisser ME, Giesecke T, Grant MA, Petzke F, Williams DA, Clauw DJ (2004) Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain 127:835–843PubMedGoogle Scholar
  46. Greenspan JD, Winfield JA (1992) Reversible pain and tactile deficits associated with a cerebral tumor compressing the posterior insula and parietal operculum. Pain 50:29–39PubMedGoogle Scholar
  47. Greenspan JD, Lee RR, Lenz FA (1999) Pain sensitivity alterations as a function of lesion location in the parasylvian cortex. Pain 81:273–282PubMedGoogle Scholar
  48. Head H, Holmes G (1911) Sensory disturbances from cerebral lesions. Brain 34:102–254Google Scholar
  49. Hofbauer RK, Rainville P, Duncan GH, Bushnell MC (2001) Cortical representation of the sensory dimension of pain. J Neurophysiol 86:402–411PubMedGoogle Scholar
  50. Hubel DH, Wiesel TN (1968) Receptive fields and functional architecture of monkey striate cortex. J Physiol 195:215–243PubMedGoogle Scholar
  51. Hurt RW, Ballantine HT Jr (1973) Stereotactic anterior cingulate lesions for persistent pain: a report on 68 cases. Clin Neurosurg 21:334–351Google Scholar
  52. Hutchison WD, Davis KD, Lozano AM, Tasker RR, Dostrovsky JO (1999) Pain-related neurons in the human cingulate cortex. Nat Neurosci 2:403–405PubMedGoogle Scholar
  53. Iannetti GD, Zambreanu L, Cruccu G, Tracey I (2005) Operculoinsular cortex encodes pain intensity at the earliest stages of cortical processing as indicated by amplitude of laser-evoked potentials in humans. Neuroscience 131:199–208PubMedGoogle Scholar
  54. Iannetti GD, Hughes NP, Lee MC, Mouraux A (2008) Determinants of laser-evoked EEG responses: pain perception or stimulus saliency? J Neurophysiol 100:815–828PubMedGoogle Scholar
  55. Iannetti GD, Lee MC, Mouraux A (2010) A multisensory investigation of the functional significance of the “pain matrix”. 13th World Congress on Pain, Montreal, CanadaGoogle Scholar
  56. Imig TJ, Adrian HO (1977) Binaural columns in the primary field (A1) of cat auditory cortex. Brain Res 138:241–257PubMedGoogle Scholar
  57. Ingvar M (1999) Pain and functional imaging. Philos Trans R Soc Lond B Biol Sci 354:1347–1358PubMedGoogle Scholar
  58. Ingvar M, Hsieg J-C (1999) The image of pain. In: Wall PD, Melzack R (eds) The textbook of pain, 4th edn. Churchill Livingstone, EdinburghGoogle Scholar
  59. Isnard J, Guenot M, Ostrowsky K, Sindou M, Mauguiere F (2000) The role of the insular cortex in temporal lobe epilepsy. Ann Neurol 48:614–623PubMedGoogle Scholar
  60. Isnard J, Guenot M, Sindou M, Mauguiere F (2004) Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study. Epilepsia 45:1079–1090PubMedGoogle Scholar
  61. Itti L, Koch C (2001) Computational modelling of visual attention. Nat Rev Neurosci 2:194–203PubMedGoogle Scholar
  62. Jackson PL, Meltzoff AN, Decety J (2005) How do we perceive the pain of others? A window into the neural processes involved in empathy. Neuroimage 24:771–779PubMedGoogle Scholar
  63. Jones A (1998a) The pain matrix and neuropathic pain. Brain 121(Pt 5):783–784PubMedGoogle Scholar
  64. Jones EG (1998b) Viewpoint: the core and matrix of thalamic organization. Neuroscience 85:331–345PubMedGoogle Scholar
  65. Jones EG (2002) Thalamic circuitry and thalamocortical synchrony. Philos Trans R Soc Lond B Biol Sci 357:1659–1673PubMedGoogle Scholar
  66. Kaas JH, Collins CE (2001) The organization of sensory cortex. Curr Opin Neurobiol 11:498–504PubMedGoogle Scholar
  67. Kakigi R, Shibasaki H (1992) Mechanisms of pain relief by vibration and movement. J Neurol Neurosurg Psychiatry 55:282–286PubMedGoogle Scholar
  68. Kakigi R, Inui K, Tran DT, Qiu Y, Wang X, Watanabe S, Hoshiyama M (2004) Human brain processing and central mechanisms of pain as observed by electro- and magneto-encephalography. J Chin Med Assoc 67:377–386PubMedGoogle Scholar
  69. Kandel E, Schwartz J, Jessel T (2000) Principles of neural science. McGraw, HillGoogle Scholar
  70. Kayser C, Petkov CI, Lippert M, Logothetis NK (2005) Mechanisms for allocating auditory attention: an auditory saliency map. Curr Biol 15:1943–1947PubMedGoogle Scholar
  71. Kenshalo DR, Douglass DK (1995) The role of the cerebral cortex in the experience of pain. In: Bromm B, Desmedt JE (eds) Pain and the brain: from nociception to cognition. Raven Press, New York, pp 21–34Google Scholar
  72. Kenshalo DR Jr, Isensee O (1983) Responses of primate SI cortical neurons to noxious stimuli. J Neurophysiol 50:1479–1496PubMedGoogle Scholar
  73. Kenshalo DR, Iwata K, Sholas M, Thomas DA (2000) Response properties and organization of nociceptive neurons in area 1 of monkey primary somatosensory cortex. J Neurophysiol 84:719–729PubMedGoogle Scholar
  74. Knudsen EI (2007) Fundamental components of attention. Annu Rev Neurosci 30:57–78PubMedGoogle Scholar
  75. Kunde V, Treede RD (1993) Topography of middle-latency somatosensory evoked potentials following painful laser stimuli and non-painful electrical stimuli. Electroencephalogr Clin Neurophysiol 88:280–289PubMedGoogle Scholar
  76. Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R et al (1992) Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci USA 89:5675–5679PubMedGoogle Scholar
  77. Lee MC, Mouraux A, Iannetti GD (2009) Characterizing the cortical activity through which pain emerges from nociception. J Neurosci 29:7909–7916PubMedGoogle Scholar
  78. Legrain V, Guerit JM, Bruyer R, Plaghki L (2002) Attentional modulation of the nociceptive processing into the human brain: selective spatial attention, probability of stimulus occurrence, and target detection effects on laser evoked potentials. Pain 99:21–39PubMedGoogle Scholar
  79. Legrain V, Guerit JM, Bruyer R, Plaghki L (2003) Electrophysiological correlates of attentional orientation in humans to strong intensity deviant nociceptive stimuli, inside and outside the focus of spatial attention. Neurosci Lett 339:107–110PubMedGoogle Scholar
  80. Legrain V, Damme SV, Eccleston C, Davis KD, Seminowicz DA, Crombez G (2009a) A neurocognitive model of attention to pain: behavioral and neuroimaging evidence. Pain 144:230–232PubMedGoogle Scholar
  81. Legrain V, Perchet C, Garcia-Larrea L (2009b) Involuntary orienting of attention to nociceptive events: neural and behavioral signatures. J Neurophysiol 102:2423–2434PubMedGoogle Scholar
  82. Logothetis NK (2008) What we can do and what we cannot do with fMRI. Nature 453:869–878PubMedGoogle Scholar
  83. Loveless N, Hari R, Hamalainen M, Tiihonen J (1989) Evoked responses of human auditory cortex may be enhanced by preceding stimuli. Electroencephalogr Clin Neurophysiol 74:217–227PubMedGoogle Scholar
  84. Lui F, Duzzi D, Corradini M, Serafini M, Baraldi P, Porro CA (2008) Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli. Pain 138:362–374PubMedGoogle Scholar
  85. Mauguiere F, Courjon J (1978) Somatosensory epilepsy. A review of 127 cases. Brain 101:307–332PubMedGoogle Scholar
  86. Melzack R (1989) Phantom limbs, the self and the brain. Can Psychol 30:1–16Google Scholar
  87. Melzack R (2005) Evolution of the neuromatrix theory of pain. The Prithvi Raj Lecture: presented at the third World Congress of World Institute of Pain, Barcelona 2004. Pain Pract 5:85–94PubMedGoogle Scholar
  88. Mesulam MM (1998) From sensation to cognition. Brain 121(Pt 6):1013–1052PubMedGoogle Scholar
  89. Miller G (2009) Neuroscience. Brain scans of pain raise questions for the law. Science 323:195PubMedGoogle Scholar
  90. Moisset X, Bouhassira D (2007) Brain imaging of neuropathic pain. Neuroimage 37(1):S80–S88PubMedGoogle Scholar
  91. Mountcastle VB (1957) Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J Neurophysiol 20:408–434PubMedGoogle Scholar
  92. Mountcastle VB, Davies PW, Berman AL (1957) Response properties of neurons of cat’s somatic sensory cortex to peripheral stimuli. J Neurophysiol 20:374–407PubMedGoogle Scholar
  93. Mouraux A, Iannetti GD (2008) A review of the evidence against the “first come first served” hypothesis. Comment on Truini et al. [Pain 2007; 131:43–47]. Pain 136:219–221; author reply 222–213Google Scholar
  94. Mouraux A, Iannetti GD (2009) Nociceptive laser-evoked brain potentials do not reflect nociceptive-specific neural activity. J Neurophysiol 101:3258–3269PubMedGoogle Scholar
  95. Mouraux A, Plaghki L (2007) Cortical interactions and integration of nociceptive and non-nociceptive somatosensory inputs in humans. Neuroscience 150:72–81PubMedGoogle Scholar
  96. Mouraux A, Guerit JM, Plaghki L (2003) Non-phase locked electroencephalogram (EEG) responses to CO2 laser skin stimulations may reflect central interactions between Aδ- and C-fibre afferent volleys. Clin Neurophysiol 114:710–722PubMedGoogle Scholar
  97. Mouraux A, Guerit JM, Plaghki L (2004) Refractoriness cannot explain why C-fiber laser-evoked brain potentials are recorded only if concomitant Adelta-fiber activation is avoided. Pain 112:16–26PubMedGoogle Scholar
  98. Naatanen R, Picton T (1987) The N1 wave of the human electric and magnetic response to sound: a review and an analysis of the component structure. Psychophysiology 24:375–425PubMedGoogle Scholar
  99. Naatanen R, Paavilainen P, Rinne T, Alho K (2007) The mismatch negativity (MMN) in basic research of central auditory processing: a review. Clin Neurophysiol 118:2544–2590PubMedGoogle Scholar
  100. Nahra H, Plaghki L (2003) Modulation of perception and neurophysiological correlates of brief CO2 laser stimuli in humans using concurrent large fiber stimulation. Somatosens Mot Res 20:139–147PubMedGoogle Scholar
  101. Ohara S, Crone NE, Weiss N, Treede RD, Lenz FA (2004) Amplitudes of laser evoked potential recorded from primary somatosensory, parasylvian and medial frontal cortex are graded with stimulus intensity. Pain 110:318–328PubMedGoogle Scholar
  102. Ostrowsky K, Magnin M, Ryvlin P, Isnard J, Guenot M, Mauguiere F (2002) Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. Cereb Cortex 12:376–385PubMedGoogle Scholar
  103. Plaghki L, Delisle D, Godfraind JM (1994) Heterotopic nociceptive conditioning stimuli and mental task modulate differently the perception and physiological correlates of short CO2 laser stimuli. Pain 57:181–192PubMedGoogle Scholar
  104. Ploghaus A, Tracey I, Gati JS, Clare S, Menon RS, Matthews PM, Rawlins JN (1999) Dissociating pain from its anticipation in the human brain. Science 284:1979–1981PubMedGoogle Scholar
  105. Ploner M, Gross J, Timmermann L, Schnitzler A (2002) Cortical representation of first and second pain sensation in humans. Proc Natl Acad Sci USA 99:12444–12448PubMedGoogle Scholar
  106. Porro CA (2003) Functional imaging and pain: behavior, perception, and modulation. Neuroscientist 9:354–369PubMedGoogle Scholar
  107. Porro CA, Cettolo V, Francescato MP, Baraldi P (1998) Temporal and intensity coding of pain in human cortex. J Neurophysiol 80:3312–3320PubMedGoogle Scholar
  108. Raij TT, Vartiainen NV, Jousmaki V, Hari R (2003) Effects of interstimulus interval on cortical responses to painful laser stimulation. J Clin Neurophysiol 20:73–79PubMedGoogle Scholar
  109. Rainville P (2002) Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol 12:195–204PubMedGoogle Scholar
  110. Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC (1997) Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277:968–971PubMedGoogle Scholar
  111. Robinson CJ, Burton H (1980) Somatotopographic organization in the second somatosensory area of M. fascicularis. J Comp Neurol 192:43–67PubMedGoogle Scholar
  112. Schnitzler A, Ploner M (2000) Neurophysiology and functional neuroanatomy of pain perception. J Clin Neurophysiol 17:592–603PubMedGoogle Scholar
  113. Schweinhardt P, Bountra C, Tracey I (2006) Pharmacological FMRI in the development of new analgesic compounds. NMR Biomed 19:702–711PubMedGoogle Scholar
  114. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27:2349–2356PubMedGoogle Scholar
  115. Sikes RW, Vogt BA (1992) Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 68:1720–1732PubMedGoogle Scholar
  116. Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD (2004) Empathy for pain involves the affective but not sensory components of pain. Science 303:1157–1162PubMedGoogle Scholar
  117. Sokolov EN (1975) The neuronal mechanisms of the orienting reflex. In: Sokolov EN, Vinogradova OS (eds) The neuronal mechanisms of the orienting reflex. Lawrence Erlbaum Associates, Hillsdale, pp 217–235Google Scholar
  118. Speckmann E, Elger C (1999) Introduction to the neurophysiological basis of the EEG and DC potentials. In: Niedermeyer E, Lopes Da Silva F (eds) Electroencephalography. Basic principles, clinical applications, and related fields. Lippincott Williams and Wilkins, Baltimore, pp 15–27Google Scholar
  119. Starr CJ, Sawaki L, Wittenberg GF, Burdette JH, Oshiro Y, Quevedo AS, Coghill RC (2009) Roles of the insular cortex in the modulation of pain: insights from brain lesions. J Neurosci 29:2684–2694PubMedGoogle Scholar
  120. Stern J, Jeanmonod D, Sarnthein J (2006) Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients. Neuroimage 31:721–731PubMedGoogle Scholar
  121. Stowell H (1984) Event related brain potentials and human pain: a first objective overview. Int J Psychophysiol 1:137–151PubMedGoogle Scholar
  122. Talbot JD, Marrett S, Evans AC, Meyer E, Bushnell MC, Duncan GH (1991) Multiple representations of pain in human cerebral cortex. Science 251:1355–1358PubMedGoogle Scholar
  123. Timmermann L, Ploner M, Haucke K, Schmitz F, Baltissen R, Schnitzler A (2001) Differential coding of pain intensity in the human primary and secondary somatosensory cortex. J Neurophysiol 86:1499–1503PubMedGoogle Scholar
  124. Tolle TR, Kaufmann T, Siessmeier T, Lautenbacher S, Berthele A, Munz F, Zieglgansberger W, Willoch F, Schwaiger M, Conrad B, Bartenstein P (1999) Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Ann Neurol 45:40–47PubMedGoogle Scholar
  125. Tracey I (2005) Nociceptive processing in the human brain. Curr Opin Neurobiol 15:478–487PubMedGoogle Scholar
  126. Tracey I, Mantyh PW (2007) The cerebral signature for pain perception and its modulation. Neuron 55:377–391PubMedGoogle Scholar
  127. Treede RD (2006) Chapter 1 pain and hyperalgesia: definitions and theories. Handb Clin Neurol 81:3–10PubMedGoogle Scholar
  128. Treede RD, Kenshalo DR, Gracely RH, Jones AK (1999) The cortical representation of pain. Pain 79:105–111PubMedGoogle Scholar
  129. Truini A, Rossi P, Galeotti F, Romaniello A, Virtuoso M, De Lena C, Leandri M, Cruccu G (2004) Excitability of the Adelta nociceptive pathways as assessed by the recovery cycle of laser evoked potentials in humans. Exp Brain Res 155:120–123PubMedGoogle Scholar
  130. Truini A, Galeotti F, Cruccu G, Garcia-Larrea L (2007) Inhibition of cortical responses to Adelta inputs by a preceding C-related response: testing the “first come, first served” hypothesis of cortical laser evoked potentials. Pain 131:341–347PubMedGoogle Scholar
  131. Valeriani M, Betti V, Le Pera D, De Armas L, Miliucci R, Restuccia D, Avenanti A, Aglioti SM (2008) Seeing the pain of others while being in pain: a laser-evoked potentials study. Neuroimage 40:1419–1428PubMedGoogle Scholar
  132. Van Damme S, Legrain V, Vogt J, Crombez G (2010) Keeping pain in mind: a motivational account of attention to pain. Neurosci Biobehav Rev 34:204–213PubMedGoogle Scholar
  133. Wall PD (1995) Independent mechanisms converge on pain. Nat Med 1:740–741PubMedGoogle Scholar
  134. Wang AL, Mouraux A, Liang M, Iannetti GD (2008) The enhancement of the N1 wave elicited by sensory stimuli presented at very short inter-stimulus intervals is a general feature across sensory systems. PLoS ONE 3:e3929PubMedGoogle Scholar
  135. Wang AL, Mouraux A, Meng L, Iannetti GD (in press) Stimulus novelty and not neural refractoriness explains the repetition suppression of laser-evoked potentials (LEPs). J NeurophysiolGoogle Scholar
  136. Whitsel BL, Petrucelli LM, Werner G (1969) Symmetry and connectivity in the map of the body surface in somatosensory area II of primates. J Neurophysiol 32:170–183PubMedGoogle Scholar
  137. Whitsel BL, Favorov OV, Li Y, Quibrera M, Tommerdahl M (2009) Area 3a neuron response to skin nociceptor afferent drive. Cereb Cortex 19:349–366PubMedGoogle Scholar
  138. Whyte J (2008) Clinical implications of the integrity of the pain matrix. Lancet Neurol 7:979–980PubMedGoogle Scholar
  139. Yamamura H, Iwata K, Tsuboi Y, Toda K, Kitajima K, Shimizu N, Nomura H, Hibiya J, Fujita S, Sumino R (1996) Morphological and electrophysiological properties of ACCx nociceptive neurons in rats. Brain Res 735:83–92PubMedGoogle Scholar
  140. Yantis S (2008) The neural basis of selective attention: cortical sources and targets of attentional modulation. Curr Dir Psychol Sci 17:86–90PubMedGoogle Scholar
  141. Young GB, Blume WT (1983) Painful epileptic seizures. Brain 106(Pt 3):537–554PubMedGoogle Scholar

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© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Neuroscience, Physiology and PharmacologyUniversity College LondonLondonUK
  2. 2.Institute of Neurosciences (IONS)Université catholique de LouvainBrusselsBelgium

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