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Direct evidence of nociceptive input to human anterior cingulate gyrus and parasylvian cortex

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Abstract

Many lines of evidence implicate the anterior cingulate cortex (ACC, Brodmann’s area [BA] 24) and parasylvian cortex in pain perception. Clinical studies demonstrate alterations in pain and temperature sensation after lesions of these structures. Imaging studies reveal increased blood flow in ACC and parasylvian cortex, both ipsilateral and contralateral to painful stimuli. Additionally, painful stimuli evoke potentials that seem t arise from these cortical structures. Short-duration cutaneous stimulation with a CO2 laser evokes painrelated potentials (LEPs) with a vertex maximum and an initial negative peak followed by a positive wave. The cutaneous laser stimulus evokes a pure pain sensation due to selective activation of cutaneous nociceptors. Electrical source modeling has suggested that the vertex maximum of the scalp LEP arises, in part, from generators in the cingulate gyrus and parasylvian cortex. Thus, imaging and electrophysiologic studies suggest that these cortical structures are activated by painful stimuli. However, these studies incorporate multiple assumptions and therefore do not establish the presence of nociceptive inputs to ACC and parasylvian cortex. We review our recent reports of intracranial potentials evoked by painful stimuli. These studies provide direct evidence of nociceptive inputs to the human ACC and parasylvian cortex

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References and Recommended Reading

  1. Casey KL: The problem of defining pain. Neurosci Res Program Bull 1978, 16:9–13.

    Google Scholar 

  2. Melzack R,Casey KL: Sensory, motivational, and central control determinants of pain. In The Skin Senses. Edited by Kenshalo D. Springfield: Thomas; 1968:423–443.

    Google Scholar 

  3. Kenshalo DRJr,Willis WD Jr: The role of the cerebral cortex in pain sensation. In Cerebral Cortex, Normal and Altered States of Function, vol 9. Edited by Peters A, Jones EG. New York: Plenum Press; 1991:153–212.

    Chapter  Google Scholar 

  4. Berthier M,Starkstein S,Leiguarda R: Asymbolia for pain: a sensory-limbic disconnection syndrome. Ann Neurol 1988, 24:41–49.

    Article  CAS  PubMed  Google Scholar 

  5. Talbot JD,Marrett S,Evans AC, et al.: Multiple representations of pain in human cerebral cortex. Science 1991, 251:1355–1358.

    Article  CAS  PubMed  Google Scholar 

  6. Casey KL,Minoshima S,Berger KL, et al.: Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli. J Neurophysiol 1994, 71:802–807.

    CAS  PubMed  Google Scholar 

  7. Coghill RC,Talbot JD,Evans AC, et al.: Distributed processing of pain and vibration by the human brain. J Neurosci 1994, 14:4095–4108.

    CAS  PubMed  Google Scholar 

  8. Vogt BA,Derbyshire S,Jones AKP: Pain processing in four regions of human cingulate cortex localized with co-registered PET and MRI. Eur J Neurosci 1996, 8:1461–1473.

    Article  CAS  PubMed  Google Scholar 

  9. Craig AD,Reiman EM,Evans A, et al.: Functional imaging of an illusion of pain. Nature 1996, 384:258–260.

    Article  CAS  PubMed  Google Scholar 

  10. Rainville P,Duncan GH,Price DD, et al.: Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 1997, 277:968–971. Report of ACC activation related to increased unpleasantness of pain.

    Article  CAS  PubMed  Google Scholar 

  11. Casey KL,Minoshima S,Morrow TJ, et al.: Comparison of human cerebral activation patterns during cutaneous warmth, heat and deep cold pain. J Neurophysiol 1996, 76:571–581.

    CAS  PubMed  Google Scholar 

  12. Mehler WR: The anatomy of the so-called "pain tract" in man: an analysis of the course and distribution of the ascending fibers of the fasciculus anterolateralis. In Basic Research in Paraplegia. Edited by French JD, Porter RW. Springfield: Thomas; 1962:26–55.

    Google Scholar 

  13. Mehler WR: Some neurological species differences— a posteriori. Ann N Y Acad Sci 1969, 167:424–468.

    Article  Google Scholar 

  14. Vogt BA,Pandya DN,Rosene DL: Cingulate cortex of the Rhesus monkey: I. Cytoarchitecture and thalamic afferents. J Comp Neurol 1987, 262:256–270.

    Article  CAS  PubMed  Google Scholar 

  15. Mehler WR,Feferman ME,Nauta WHJ: Ascending axon degeneration following anterolateral cordotomy. An experimental study in the monkey. Brain 1960, 83:718–750.

    Article  CAS  PubMed  Google Scholar 

  16. Burton H,Craig ADJr: Spinothalamic projections in cat, raccoon and monkey: a study based on anterograde transport of horseradish peroxidase. In Somatosensory Integration in the Thalamus Edited by Macchi G, Rustioni A, Spreafico R. Amsterdam: Elsevier; 1983:17–41.

    Google Scholar 

  17. Berkley KJ: Spatial relationships between the terminations of somatic sensory and motor pathways in the rostral brainstem of cats and monkeys. I. Ascending somatic sensory inputs to lateral diencephalon. J Comp Neurol 1980, 193:283–317.

    Article  CAS  PubMed  Google Scholar 

  18. Apkarian AV,Hodge CJ: Primate spinothalamic pathways: III. Thalamic terminations of the dorsolateral and ventral spinothalamic pathways. J Comp Neurol 1989, 288:493–511.

    Article  CAS  PubMed  Google Scholar 

  19. Kerr FWL: The ventral spinothalamic tract and other ascending systems of the ventral funiculus of the spinal cord. J Comp Neurol 1975, 159:335–356.

    Article  CAS  PubMed  Google Scholar 

  20. Craig AD,Bushnell MC,Zhang ET, et al.: A specific thalamic nucleus for pain and temperature sensation in macaques and humans. Nature 1994, 372:770–773.

    Article  CAS  PubMed  Google Scholar 

  21. Craig AD: The primate MDvc contains nociceptive neurons [abstract]. Soc Neurosci Abstr 1997, 23:1012.

    Google Scholar 

  22. Craig AD: Lamina I trigeminothalamic projections in th monkey [abstract]. Soc Neurosci Abstr 1990, 16:1144.

    Google Scholar 

  23. Craig AD,Zhang ET: Anterior cingulate connection from MDvc (a lamina I spinothalamic target in the medial thalamus of the monkey) [abstract]. Soc Neurosci Abst 1996, 22:111.

    Google Scholar 

  24. Bushnell MC,Duncan GH: Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues? Exp Brain Res 1989, 78:415–418.

    Article  CAS  PubMed  Google Scholar 

  25. Casey KL: Unit analysis of nociceptive mechanisms in the thalamus of the awake squirrel monkey. J Neurophysiol 1966, 29:727–750.

    CAS  PubMed  Google Scholar 

  26. Dong WK,Ryu H,Wagman IH: Nociceptive responses of neurons in medial thalamus and their relationship to spinothalamic pathways. J Neurophysiol 1978, 41:1592–1613.

    CAS  PubMed  Google Scholar 

  27. Sikes RW,Vogt BA: Nociceptive Neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 1992, 68:1720–1732.

    CAS  PubMed  Google Scholar 

  28. Hutchison WD,Davis KD,Lozano AM, et al.: Pain-related neurons in the human cingulate cortex. Nature Neurosci 1999, 2:403–405. Report that cells in human ACC are excited or inhibited by painful stimuli.

    Article  CAS  PubMed  Google Scholar 

  29. Jones AKP,Brown WD,Friston KJ, et al.: Cortical and subcortical localization of response to pain in man using positron emission tomography. Proc R Soc Lond B Biol Sc 1991, 244:39–44.

    Article  CAS  Google Scholar 

  30. Derbyshire SWG,Jones AKP,Gyulai F, et al.: Pain processing during three levels of noxious stimulation produces different pattern of central activity. Pain 1997, 73:471–445. Report of anatomic differences in central activation as a function of central activity.

    Article  Google Scholar 

  31. Davis KD,Taylor SJ,Crawley AP, et al.: Functional MRI of pain- and attention-related activation in the human cingulate cortex. J Neurophysiol 1997, 77:3370–3380. Report of differences in the location of activation by pain- an attention-related paradigm.

    CAS  PubMed  Google Scholar 

  32. Hirai T,Jones EG: A new parcellation of the human thalamus on the basis of histochemical staining. Brain Res Rev 1989, 14:1–34.

    Article  CAS  PubMed  Google Scholar 

  33. Lenz FA,Dougherty PM: Pain processing in the human thalamus. In Thalamus, vol 2. Edited by Steriade M, Jones EG, McCormick DA. Oxford: Elsevier; 1997:617–651. Review of human thalamic anatomy and physiology of pain-related activity.

    Google Scholar 

  34. Van Buren JM,Borke RC: Variations and Connections of the Human Thalamus. Berlin: Springer Verlag; 1972.

    Book  Google Scholar 

  35. Lenz FA,Seike M,Lin YC, et al.: Neurons in the area of human thalamic nucleus ventralis caudalis respond to painful heat stimuli. Brain Res 1993, 623:235–240.

    Article  CAS  PubMed  Google Scholar 

  36. Lenz FA,Gracely RH,Rowland LH, et al.: A population of cells in the human principal sensory nucleus respond to painful mechanical stimuli. Neurosci Lett 1994, 180:46–50.

    Article  CAS  PubMed  Google Scholar 

  37. Lee JI, Doughert PM, Antezana D, et al.: Responses of neurons in the region of human thalamic principle somatic sensory nucleus to mechanical and thermal stimuli graded into the painful range. J Comp Neurol 1999, in press. The response of cells in human thalamic ventral posterior nucleus is graded into the painful range for both mechanical and thermal stimuli. The activity of these cells very likely signals pain.

  38. Davis KD,Lozano AM,Manduch M, et al.: Thalamic relay site for cold perception in humans. J Neurophysiol 1999, 81:1970–1973. Report of pain and cold temperature-related neuronal activity in putative human ventral medial posterior nucleus.

    CAS  PubMed  Google Scholar 

  39. Dostrovsky JO,Wells FEB,Tasker RR: Pain evoked by stimulation in human thalamus. In International Symposium on Processing Nociceptive Information. Edited by Sjigenaga Y. Amsterdam: Elsevier; 1991.

    Google Scholar 

  40. Halliday AM,Logue V: Painful sensations evoked by electrical stimulation in the thalamus. In Neurophysiology Studied in Man. Edited by Somjen GG. Amsterdam: Excerpta Medica; 1972:221–230.

    Google Scholar 

  41. Hassler R,Reichert T: Klinische und anatomische Befunde bei stereotaktischen Schmerzoperationen im Thalamus. Arch Psychiatry Nervenkr 1959, 200:93–122.

    Article  CAS  Google Scholar 

  42. Lenz FA,Gracely RH,Romanoski AJ, et al.: Stimulation in the human somatosensory thalamus can reproduce both the affective and sensory aspects of previously experienced pain. Nat Med 1995, 1:910–913.

    Article  CAS  PubMed  Google Scholar 

  43. Lenz FA,Seike M,Lin YC, et al.: Thermal and pain sensations evoked by microstimulation in the area of the human ventrocaudal nucleus (Vc). J Neurophysiol 1993, 70:200–212.

    CAS  PubMed  Google Scholar 

  44. Lenz FA,Gracely RH,Hope EJ, et al.: The sensation of angina can be evoked by stimulation of the human thalamus. Pain 1994, 59:119–125.

    Article  CAS  PubMed  Google Scholar 

  45. Davis KD,Tasker RR,Kiss ZHT, et al.: Visceral pain evoked by thalamic microstimulation in humans. Neuroreport 1995, 6:369–374.

    Article  CAS  PubMed  Google Scholar 

  46. Walker AE: Relief of pain by mesencephalic tractotomy. Arch Neurol Psychiatry 1942, 48:865–883.

    Article  Google Scholar 

  47. Lenz FA,Gracely RH,Zirh AT, et al.: The sensory-limbic model of pain memory. Pain Forum 1997, 6:22–31. Proposal of the sensory-limbic hypothesis that SII and insular cortex are involved in the learned component of the affective dimensions of pain on the basis of connections with the limbic system.

    Article  Google Scholar 

  48. Kenshalo DR,Isensee O: Responses of primate SI corticalneurons to noxious stimuli. J Neurophysiol 1983, 50:1479–1496.

    PubMed  Google Scholar 

  49. Kenshalo DR Jr,Chudler EH,Anton F, et al.: SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation. Brain Res 1988, 454:378–382.

    Article  PubMed  Google Scholar 

  50. Robinson CJ,Burton H: Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory and granular insular cortical areas of M. fascicularis. J Comp Neurol 1980, 192:93–108.

    Article  CAS  PubMed  Google Scholar 

  51. Dostrovsky JO,Craig AD: Nociceptive neurons in the primate insular cortex [abstract]. Soc Neurosci Abstr 1996, 22:111.

    Google Scholar 

  52. Dong W,Chudler E,Sugiyama K, et al.: Somatosensory, multisensory, and task-related neurons in cortical area 7b (PF) of unanesthetized monkeys. J Neurophysiol 1994, 72:542–564.

    CAS  PubMed  Google Scholar 

  53. Dong W,Salonen L,Kawakami Y, et al.: Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkeys. Brain Res 1989, 484:314–324.

    Article  CAS  PubMed  Google Scholar 

  54. Chudler E,Dong W,Kawakami Y: Tooth pulp-evoked potentials in the monkey:cortical surface and intracortical distribution. Pain 1985, 22:221–233.

    Article  CAS  PubMed  Google Scholar 

  55. Chudler E,Dong W,Kawakami Y: Cortical nociceptive responses and behavioral correlates in the monkey. Brain Res 1986, 397:47–60.

    Article  CAS  PubMed  Google Scholar 

  56. Coghill RC,Sang CN,Ma J, et al.: Distributed representation of painful stimulus intensity in the human brain [abstract]. Soc Neurosci Abstr 1997, 23:439.

    Google Scholar 

  57. Bromm B,Treede R: Nerve fibre discharges, cerebral potentials and sensations induced by carbon dioxide laser stimulation. Hum Neurobiol 1984, 3:33–40.

    CAS  PubMed  Google Scholar 

  58. Carmon A,Dotan Y,Sarne Y: Correlation of subjective pain experience with cerebral evoked responses to noxious thermal stimulations. Exp Brain Res 1978, 33:445–453.

    Article  CAS  PubMed  Google Scholar 

  59. Treede R,Kief S,Hölzer T, et al.: Late somatosensory evoked cerebral potentials in response to cutaneous heat stimuli. Electroencephalogr Clin Neurophysiol 1988, 70:429–441.

    Article  CAS  PubMed  Google Scholar 

  60. Kunde V,Treede RD: Topography of middle-latency somatosensory evoked potentials following painful laser stimuli and non-painful electrical stimuli. Electroencephalogr Clin Neurophysiol 1993, 88:280–289.

    Article  CAS  PubMed  Google Scholar 

  61. Miyazaki M,Shibasaki H,Kanda M, et al.: Generator mechanism of pain-related evoked potentials following CO2 laser stimulation of the hand: scalp topography and effect of predictive warning signal. J Clin Neurophysiol 1994, 11:242–254.

    Article  CAS  PubMed  Google Scholar 

  62. Beydoun A,Morrow T,Shen JF, et al.: Variability of laserevoked potentials: attention, arousal and lateralized differences. Electroencephalogr Clin Neurophysiol 1993, 88:171–181.

    Article  Google Scholar 

  63. Beydoun A,Morrow TJ,Schen JF, et al.: Variability of laser evoked potentials: attention, arousal and lateralized differences. Electroencephalogr Clin Neurophysiol 1993, 88:173–181.

    Article  CAS  PubMed  Google Scholar 

  64. Zaslansky R,Sprecher E,Tenke CE, et al.: The P300 in pain evoked potentials. Pain 1995, 66:39–49.

    Article  Google Scholar 

  65. Kitamura Y,Kakigi R,Hoshiyama M, et al.: Pain-related somatosensory evoked magnetic fields. Electroencephalogr Clin Neurophysiol 1995, 95:463–474.

    Article  CAS  PubMed  Google Scholar 

  66. Tarkka IM,Treede RD: Equivalent electrical source analysis of pain-related somatosensory evoked potentials elicited by a CO2 laser. J Clin Neurophysiol 1993, 10:513–519.

    Article  CAS  PubMed  Google Scholar 

  67. Chen ACN,Bromm B: Pain-related generators of laser-evoked brain potentials: brain mapping and dipole modelling. In Pain and the Brain: From Nociception to Cognition. Edited by Bromm B, Desmedt JE. New York: Raven Press; 1995:245–266.

    Google Scholar 

  68. Valerianai M,Rambaud L,Mauguiere F: Scalp topography and dipolar source modelling of potentials evoked by carbon dioxide laser stimulation. Electroencephalogr Clin Neurophysiol 1996, 100:343–353.

    Article  Google Scholar 

  69. Kakigi R,Koyama S,Hoshiyama M, et al.: Pain-related magnetic fields following painful CO2 laser stimulation in man. Neurosci Lett 1995, 192:45–48.

    Article  CAS  PubMed  Google Scholar 

  70. Hari R,Kaukoranta E,Reinikainen K, et al.: Neuromagneti localization of cortical activity evoked by painful dental stimulation in man. Neurosci Lett 1983, 42:77–82.

    Article  CAS  PubMed  Google Scholar 

  71. Huttunen J,Kobal G,Kaukoranta E, et al.: Cortical responses to painful CO2 stimulation of the nasal mucosa: a magnetoencephalographic study in man. Electroencephalogr Clin Neurophysiol 1986, 64:347–349.

    Article  CAS  PubMed  Google Scholar 

  72. Lenz FA,Rios MR,Zirh TA, et al.: Painful stimuli evoke potentials recorded over the human anterior cingulate gyrus. J Neurophysiol 1998, 9:2231–2234. Report of potentials recorded from human ACC in response to painful cutaneous stimuli.

    Google Scholar 

  73. Lenz FA,Rios MR,Chau D, et al.: Painful stimuli evoke potentials recorded over the parasylvian cortex in humans. J Neurophysiol 1998, 80:2077–2088. Report of potentials recorded from human parasylvian cortex in response to painful cutaneous stimuli.

    CAS  PubMed  Google Scholar 

  74. Boatman D,Hall C,Goldstein MH, et al.: Neuroperceptual differences in consonant and vowel discrimination as revealed by direct cortical electrical interference. Cortex 1997, 33:83–89.

    Article  CAS  PubMed  Google Scholar 

  75. Lesser RP,Gordon B,Uematsu S: Electrical stimulation and language. J Clin Neurophysiol 1994, 11:191–204.

    Article  CAS  PubMed  Google Scholar 

  76. Ranck JB: Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 1975, 98:417–440.

    Article  PubMed  Google Scholar 

  77. Jasper HH: The Ten-Twenty Electrode System of the International Federation. Electroencephalogr Clin Neurophysiol 1958, 10:371–375.

    Google Scholar 

  78. Valeriani M,Rambaud L,Mauguiere F: Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand. Electroencephalogr Clin Neurophysiol 1996, 100:343–353.

    Article  CAS  PubMed  Google Scholar 

  79. Frot M,Rambaud L,Guenot M, et al.: Intracortical recordings of early pain-related CO2 laser evoked potientials in the human second somatosensory (SII) area. Clin Neurophysiol 1999, 110:133–145. Report of human intracortical potentials recorded in human parietal operculum in response to painful stimuli.

    Article  CAS  PubMed  Google Scholar 

  80. Merskey H: Classification of chronic pain. Pain 1986, S3:S1-S225.

    Google Scholar 

  81. Folz EL,White LE: Pain “relief” by frontal cingulotomy. J Neurosurg 1962, 19:89–100.

    Article  Google Scholar 

  82. Hurt RW,Ballantine HT: Stereotactic anterior cingulate lesions for persistent pain: a report of 68 cases. Clin Neurosurg 1973, 21:334–351.

    Google Scholar 

  83. Hassenbusch SJ,Pillay PK,Barnett GH: Radiofrequency cingulot omy for intractable cancer pain using stereotaxis guided by magnetic resonance imaging. Neurosurgery 1990, 27:220 223.

    Article  PubMed  Google Scholar 

  84. Bouckoms AF: Psychosurgery In Textbook of Pain. Edited by Wall PD, Melzack R. Edinburgh: Churchill Livingstone; 1984:666–676.

    Google Scholar 

  85. Davis KD,Hutchinson WD,Lozano AM, et al.: Altered pain and temperature perception following cingulotomy and capsulotomy in a patient with schizoaffective disorder. Pain 1994, 59:189–199.

    Article  CAS  PubMed  Google Scholar 

  86. Greenspan J,Joy SE,McGillis SLB, et al.: Selective pain deficits associated with an extensive posterolateral thalamic lesion. Pain 1997, 72:13–25.

    Article  CAS  PubMed  Google Scholar 

  87. Greenspan JD, Lee RR, Lenz FA: Pain sensitivity alteration as a function of lesion location in the parasylvian cortex. Pain 1999, in press. Report that sensory and motivational aspects of pain are disabled by lesions of parietal operculum and insula, respectively.

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Rios}, M., Treede, R.D., Lee, J.I. et al. Direct evidence of nociceptive input to human anterior cingulate gyrus and parasylvian cortex. Current Review of Pain 3, 256–264 (1999). https://doi.org/10.1007/s11916-999-0043-8

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