PET-Scan and Electrophysiological Assessment of Neuromodulation Procedures for Pain Control

  • L. García-Larrea
  • R. Peyron
  • E. Mauguière
  • B. Laurent
Conference paper
Part of the Topics in Anaesthesia and Critical Care book series (TIACC)


The strong inhibitory influences that electrical stimulation of the nervous system can exert on pain transmission have been repeatedly demonstrated by experimental studies in animals [1–4], prompting the use of neurostimulation strategies for the relief of chronic pain in humans. As a logical corollary of the ‘Gate control’ theory [1, 5], which postulates that non-nociceptive signals tend to inhibit those conveyed by nociceptive pathways, the neural targets of stimulation procedures have been mostly the sensory pathways mediating transmission of non-noxious information, namely large afferent peripheral fibers, spinal dorsal columns and thalamic sensory nuclei (for both historical and up-to-date reviews see 6–9]. To a lesser extent brainstem structures exerting descending antinociceptive influences, such as the periaqueductal (PGA) and periventricular (PVG) grey matter have been also been used as targets [7]. Although stimulation of central motor fibers was also shown to inhibit afferent transmission in the dorsal horn [10, 11] and to produce analgesic effects in man [12] the use of motor cortex stimulation for pain control has been documented only recently [13]. Since then, the use of MCS for analgesic purposes is being increasingly used for refractory neuropathic pain [14–19].


Neuropathic Pain Dorsal Horn Spinal Cord Stimulation Transcutaneous Electrical Nerve Stimulation Dorsal Column 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Melzack R, Wall P (1965) Pain mechanisms: a new theory. Science 150: 971–97PubMedCrossRefGoogle Scholar
  2. 2.
    Handwerker HO, Iggo A, Zimmermann M (1975) Segmental and supraspinal actions on dorsal horn neurons responding to noxious and non-noxious skin stimuli. Pain 1: 147–165PubMedCrossRefGoogle Scholar
  3. 3.
    Lindblom U, Tapper N, Wiesenfeld Z (1977) The effect of dorsal column stimulation on the nociceptive response of dorsal horn cells and its relevance for pain suppression. Pain 4: 133–144PubMedCrossRefGoogle Scholar
  4. 4.
    Gerhart KD, Yezierski RP, Fang ZR, Willis WD (1983) Inhibition of primate spinothalamic tract neurons by stimulation in ventral posterior lateral thalamic nucleus. Possible mechanisms. J. Neurophysiol 49: 406–423PubMedGoogle Scholar
  5. 5.
    Wall PD (1978) The gate-control theory of pain mechanisms. Brain 101: 1–18PubMedCrossRefGoogle Scholar
  6. 6.
    Meyerson BA (1983) Electrostimulation procedures: effects, presumed rationale, and possible mechanisms. In Bonica JL, Ed. Advances in Pain Research and Therapy. Vol. 5, New York, Raven Press pp 495–534Google Scholar
  7. 7.
    Gybels J, Kuypers R (1995) Subcortical stimulation in humans and pain. In: Desmedt JE, Bromm B, (ed) Advances in Pain Research and Therapy n°22 (Pain and the Brain), Basel, Karger pp 187–199Google Scholar
  8. 8.
    Holsheimer J (1997) Effectiveness of spinal cord stimulation in the management of chronic pain: analysis of technical drawbacks and solutions. Neurosurgery 1997 40: 990–996CrossRefGoogle Scholar
  9. 9.
    Jessurun GAJ, Dejongste MJL, Blanksma PK (1996) Current views on neurostimulation in the treatment of cardiac ischemic syndromes. Pain 66: 109–116PubMedCrossRefGoogle Scholar
  10. 10.
    Lindblom U, Ottosson JO (1957) Influence of pyramidal stimulation upon the relay of coarse cutaneous afferents in the dorsal horn. Acta Physiol Scand 38: 309–318PubMedCrossRefGoogle Scholar
  11. 11.
    Andersen P, Eccles JC, Sears TA (1962) Presynaptic inhibitory action of cerebral cortex on the spinal cord. Nature 194: 740–741Google Scholar
  12. 12.
    Adams JE, Hosobuchi Y, Fields HL (1974) Stimulation of internal capsule for relief of chronic pain. J Neurosurg 41: 740–744PubMedCrossRefGoogle Scholar
  13. 13.
    Tsubokawa T, Katayama Y, Yamamoto T et al (1991) Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir (Suppl 52 ): 137–139CrossRefGoogle Scholar
  14. 14.
    Tsubokawa T, Katayama Y, Yamamoto T et al (1993a) Chronic motor cortex stimulation in patients with thalamic pain. J Neurosurg 78: 393–401PubMedCrossRefGoogle Scholar
  15. 15.
    Meyerson BA, Lindblom U, Linderoth B et al (1993) Motor cortex stimulation as a treatment of trigeminal neuropathic pain. Acta Neurochirurg (suppl. 58 ): 150–153Google Scholar
  16. 16.
    Katayama Y, Tsubokawa T, Yamamoto T (1994) Chronic motor cortex stimulation for central deafferentation pain: experience with bulbar pain secondary to Wallenberg syndrome. Stereotact Funct Neurosurg 62: 295–299PubMedCrossRefGoogle Scholar
  17. 17.
    Katayama Y, Fukaya C, Yamamoto T (1998) Poststroke pain control by chronic motor stimulation: neurological characteristics predicting a favorable response. J Neurosurg 89: 585–591PubMedCrossRefGoogle Scholar
  18. 18.
    Ebel H, Rust D, Tronnier V et al (1996) Chronic precentral stimulation in trigeminal neuropathic pain. Acta Neurochir 138: 1300–1306CrossRefGoogle Scholar
  19. 19.
    Herregodts P, Stadnik T, Deridder F, Dhaens J (1996) Cortical stimulation for central neuropathic pain: 3-D surface MRI for easy determination of the motor cortex. In: Adv Stereotact Funct Neurosurg 11: 132–135Google Scholar
  20. 20.
    Sherrington CS (1910) Flexion-reflex of the limb, crossed extension-reflex, and reflex stepping and standing. J Physiol (Lond.) 40: 28–121Google Scholar
  21. 21.
    Hugon M (1973) Exteroceptive reflexes to stimulation of the sural nerve in normal man. In: New Developments in Electromyography and Clinical Neurophysiology, Vol. III, JE Desmedt (ed) Basel, Karger:713–729Google Scholar
  22. 22.
    Willer JC (1977) Comparative study of perceived pain and nociceptive flexion reflex in man. Pain 3: 69–80PubMedCrossRefGoogle Scholar
  23. 23.
    Willer JC (1984) Nociceptive flexion reflex as a physiological correlate of pain sensation in humans. Handbook of Physiology, Amsterdam, Elsevier pp 87–110Google Scholar
  24. 24.
    Duggan AW, Foong FW (1985) Bicuculline and spinal inhibition produced by dorsal column stimulation in the cat. Pain 22: 249–259PubMedCrossRefGoogle Scholar
  25. 25.
    Carstens E, Campbell IG (1988) Parametric and pharmacological studies of midbrain supression of the hind limb flexion withdrawal reflex in the rat. Pain, 33: 201–213PubMedCrossRefGoogle Scholar
  26. 26.
    Garcia-Larrea L., Mauguière F (1990) Electrophysiological assessment of nociception in normals and patients: the use of nociceptive spinal reflexes. Electroencephal Clin Neurophysiol (Suppl. 41 ): 102–118Google Scholar
  27. 27.
    Bathien N (1971) Réflexes spinaux chez l’Homme et niveaux d’attention. Electroenceph clin Neurophysiol 30: 32–37PubMedCrossRefGoogle Scholar
  28. 28.
    Willer JC, Boureau F, Albe-Fessard D (1979) Supraspinal influences on nociceptive flexion reflexes and pain sensation in man. Brain Res 179: 61–68PubMedCrossRefGoogle Scholar
  29. 29.
    Willer JC, Albe-Fessard D (1980) Electrophysiological evidence for a release of endogenous opiates in stress-induced `analgesia’ in man. Brain Res 198: 419–426PubMedCrossRefGoogle Scholar
  30. 30.
    Garcia-Larrea L, Charles N, Sindou M, Mauguière F (1993) Flexion reflexes following alterolateral cordotomy in man: dissociation between subjective pain and nociceptive reflex RIII. Pain 55: 139–149PubMedCrossRefGoogle Scholar
  31. 31.
    Mauguière F (1995) Description and origins of SEP components. In: Binnie C et al. (eds) Clinical Neurophysiology, Vol. 1. Oxford, Butterworth–Heinemann: 393–421Google Scholar
  32. 32.
    Bromm B, Treede RD (1991) Laser-evoked cerebral potentials in the assessment of cutaneous pain sensitivity in normal subjects and patients. Rev Neurol 147: 625–643PubMedGoogle Scholar
  33. 33.
    Arendt-Nielsen L (1991) Characteristics, detection and modulation of laser-evoked vertex potentials. Acta Anaesthesiol. Scandinavica 38 (suppl. 101): 1–44Google Scholar
  34. 34.
    Garcia-Larrea L, Peyron R, Laurent B, Mauguière F (1997) Association and dissociation between laser-evoked potentials and pain sensation. Neuroreport 8: 3785–3789PubMedCrossRefGoogle Scholar
  35. 35.
    Fox PT, Mintun MA (1989) Noninvasive functional brain mapping by change-distribution analysis of averaged PET images of H2150 tissue activity. J Nucl Med 30: 141–149PubMedGoogle Scholar
  36. 36.
    Sokoloff L, Porter A, Roland P, et al (1991) General Discussion. In: Chadwick C, Derek J, Whelan J (eds) Exploring brain functional anatomy with positron emission tomography; Ciba Foundation Symposium n°163, London, Wiley & Sons: 43–56Google Scholar
  37. 37.
    Peyron R, Laurent B, Garcia-Larrea L (2000) Functional imaging of pain: A review and meta-analysis. Neurophysiol. Clin 30: 263–288PubMedCrossRefGoogle Scholar
  38. 38.
    Hautvast RWM, Terhorst GJ, Dejong BM, et al (1997) Relative changes in regional cerebral blood flow during spinal cord stimulation in patients with refractory angina pectoris. Eur Journal Neurosci 9: 1178–1183CrossRefGoogle Scholar
  39. 39.
    Katayama Y, Tsubokawa T, Hirayama T (1986) Response of regional cerebral blood flow and oxygen metabolism to thalamic stimulation in humans as revealed by positron emission tomography. J Cereb Blood Flow Metab 6: 637–641PubMedCrossRefGoogle Scholar
  40. 40.
    Peyron R, Garcia-Larrea L, Deiber MP et al (1995) Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study. Pain 62: 275–286PubMedCrossRefGoogle Scholar
  41. 41.
    Garcia-Larrea L, Peyron R, Mertens P, et al (1999). Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain 83: 259–273PubMedCrossRefGoogle Scholar
  42. 42.
    Barolat G, Zeme S, Ketcik B (1991) Multifactorial analysis of epidural spinal cord stimulation. Stereotact Funct Neurosurg 56: 77–103PubMedCrossRefGoogle Scholar
  43. 43.
    North RB (1993). Spinal cord stimulation for chronic, intractable pain. In: Devinsky O, Beric A, Dogali M (eds) Electrical and Magnetic Stimulation of the Brain and Spinal Cord. New York, Raven Press:289–301Google Scholar
  44. 44.
    Segal R, Stacey BR, Rudy TE et al (1998) Spinal cord stimulation revisited. Neurol. Res 20: 391–396PubMedGoogle Scholar
  45. 45.
    Keravel Y, Sindou M, Blond S (1991) Stimulation and ablative neurosurgical procedures in the peripheral nerves and the spinal cord for deafferentation and neuropathic pain. In: Besson JM, Guilbaud G (eds) Lesions of Primary Afferent Fibers as a Tool for the Study of Clinical Pain. Amsterdam, Elsevier:315–334Google Scholar
  46. 46.
    Mertens P, Sindou M, Gharios B et al (1992) Spinal cord stimulation for pain treatment: prognostic value of somesthetic evoked potentials. Acta Neurochir (Wien) 117: 90–91Google Scholar
  47. 47.
    Wu Q, Garcia-Larrea L, Mertens P et al (1999) Hyperalgesia with loss of laser EPs in neuropathic pain. Pain 80: 209–214PubMedCrossRefGoogle Scholar
  48. 48.
    Hillman P, Wall PD (1969) Inhibitory and excitatory factors influencing the receptive fields of lamina V spinal cord cells. Exp Brain Res 9: 284–306PubMedGoogle Scholar
  49. 49.
    Brown AG, Hamann WC, Martin HF (1973) Interactions of cutaneous myelinated (A) and non myelinated (C) fibers on transmission through the spinocervical tract. Brain Res 53: 222–226PubMedCrossRefGoogle Scholar
  50. 50.
    Marchand S, Charest J, Li J et al (1993) Is TENS purely a placebo effect? A controlled study on chronic low back pain. Pain 54: 99–106PubMedCrossRefGoogle Scholar
  51. 51.
    Erskine A, Morley S, Pearce S (1990) Memory for pain: a review. Pain 41: 255–265PubMedCrossRefGoogle Scholar
  52. 52.
    Boureau F, Keravel Y, Hugenard P (1981) Effects of dorsal column stimulation on human spinal reflexes. Preliminary results. Pain (Suppl 1 ): 319Google Scholar
  53. 53.
    Garcia-Larrea L, Sindou M, Mauguière F (1989) Clinical use of nociceptive flexor reflex recording in functional neurosurgical procedures. Acta Neurochir Suppl (Wien) 46: 53–57CrossRefGoogle Scholar
  54. 54.
    Garcia-Larrea L, Sindou M, Mauguière F (1989) Nociceptive flexion reflexes during analgesic neurostimulation in man. Pain 39: 145–156PubMedCrossRefGoogle Scholar
  55. 55.
    Marchand S, Bushnell MC, Molina-Negro P et al (1991) The effects of dorsal column stimulation on measures of clinical and experimental pain in man. Pain 45: 249–257PubMedCrossRefGoogle Scholar
  56. 56.
    Cole JD, Illis LS, Sedwick EM (1987) Pain produced by spinal cord stimulation in a patient with allodynia and pseudo-tabes. J Neurol Neurosurg Psychiat 50: 1083–1084PubMedCrossRefGoogle Scholar
  57. 57.
    Dazinger N, Rozenberg S, Bourgeois P et al (1998) Depressive effects of segmental and heterotopic application of transcutaneous electrical nerve stimulation and piezoelectric current on lower limb nociceptive reflex in human subjects. Arch Phys Med Rehabil 79: 191–200CrossRefGoogle Scholar
  58. 58.
    Le Bars D, Dickenson AH, Besson J-M (1979) Diffuse noxious inhibitory controls: Effects on dorsal horn convergent neurons in the rat. Pain 6: 283–304PubMedCrossRefGoogle Scholar
  59. 59.
    Willer JC, Boussahira D, Le Bars D (1979). Bases neurophysiologiques du phénomène de contre-irritation: les contrôles inhibiteurs induits par stimulations nociceptives. Neurophysiol. Clin 29: 379–400CrossRefGoogle Scholar
  60. 60.
    Parise M, Garcia-Larrea L, Mertens P, Sindou M (1998) A estimulaçao medular no tratamento da dor crônica. Presentation to the XXII Brazilian Congress of Neurosurgery, Rio de Janeiro, 4–11 Sept. Book of Abstracts, pp 412Google Scholar
  61. 61.
    Nardone A, Schieppati M (1989) Influences of transcutaneous electrical stimulation of cutaneous and mixed nerves on subcortical and cortical somatosensory evoked potentials. Electroencephal clin Neurophysiol 74: 24–35CrossRefGoogle Scholar
  62. 62.
    Urasaki E, Wada S, Yasukouchi H, Yokota A (1998) Effect of transcutaneous electrical nerve stimulation (TENS) on central nervous system amplification of somatosensory input. J Neural 245: 143–148CrossRefGoogle Scholar
  63. 63.
    Ibanez V, Deiber MP, Mauguière F (1989) Interference of vibrations with input transmission in dorsal horn and cuneate nucleus in man: a study of somatosensory evoked potentials (SEPS) to electrical stimulation of median nerve and fingers. Exp Brain Res 75: 599–610PubMedCrossRefGoogle Scholar
  64. 64.
    Kakigi R, Shibasaki H (1992) Mechanisms of pain relief by vibration and movement. J Neurol Neurosurg Psychiatr 55: 282–286PubMedCrossRefGoogle Scholar
  65. 65.
    Ren B, Linderoth B, Meyerson BA (1996) Effects of spinal cord stimulation on the flexor reflex and involvement of supraspinal mechanisms: An experimental study in mononeuropathic rats. J Neurosurg 84: 244–249PubMedCrossRefGoogle Scholar
  66. 66.
    Firestone LL, Gyulai F, Mintun Met al (1996) Human brain activity response to fentanyl imaged by positron emission tomography, Anesth Analg 82: 1247–51PubMedGoogle Scholar
  67. 67.
    Adler LJ, Gyulai FE, Diehl DJ, et al (1997), Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography. Anesth Analg 84: 120–126PubMedGoogle Scholar
  68. 68.
    Duncan G., Kupers RC, Marchand S, et al (1998) Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by Positron Emission Tomography. J. Neurophysiol 80: 3326–3330PubMedGoogle Scholar
  69. 69.
    Peyron R, Garcia-Larrea L, Grégoire MC, et al (1998) Allodynia after lateral-medullary (Wallenberg) infarct. A Positron Emission Tomography (PET) study, Brain 121: 345–356PubMedCrossRefGoogle Scholar
  70. 70.
    Jones AKP, Qi LY, Fujirawa T et al (1991) In vivo distribution of opioid receptors in man in relation to the cortical projections of the medial and lateral pain systems measured with positron emission tomography, Neurosci Lett 126: 25–28PubMedCrossRefGoogle Scholar
  71. 71.
    Tsubokawa T, Katayama Y, Yamamoto T, et al (1993b) Treatment of deafferentation pain with thalamic and motor cortex stimulation: possible role of reorganization of neural circuits. VIIth World Congress on Pain. Book of Abstracts, IASP Publications, Seattle: 504–505Google Scholar
  72. 72.
    Hirayama T, Tsubokawa T, Katayama Y, et al (1990) Tonic changes in activity of thalamic lemniscal relay neurons following spino-thalamic tractotomy in cats: effects of motor cortex stimulation. Pain; (suppl. 5 ): S273CrossRefGoogle Scholar
  73. 73.
    Di Piero V, Jones AKP, Iannotti F, et al (1991) Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain, 46: 9–12PubMedCrossRefGoogle Scholar
  74. 74.
    Pagni CA, Canavero S (1995) Functional thalamic depression in a case of reversible central pain due to a spinal intramedullary cyst. Case report. J Neurosurg 83: 163–165Google Scholar
  75. 75.
    Foltz EL, White LE (1962) Pain `relief’ by frontal cingulumotomy. J Neurosurg 19: 89–100PubMedCrossRefGoogle Scholar
  76. 76.
    Vogt B, Finch DM, Olson C (1992) Functional heterogeneity in cingulate cortex: The anterior executive and posterior evaluative regions. Cerebral Cortex 2: 435–443PubMedGoogle Scholar
  77. 77.
    Devinsky O, Morrell MJ, Vogt BA (1995) Contributions of the anterior cingulate cortex to behaviour. Brain, 118: 279–306PubMedCrossRefGoogle Scholar
  78. 78.
    Lane RD, Fink GR, Chau PML, Dolan RJ (1997) Neural activation during selective attention to subjective emotional responses. Neuroreport, 8: 3969–3972PubMedCrossRefGoogle Scholar
  79. 79.
    Nuti C (1998) La stimulation antalgique du cortex precentral. Synthèse des données actuelles. Unpublished MD Thesis, University of St Etienne, France: 150 ppGoogle Scholar
  80. 80.
    Bromm B, Chen ACN (1995) Brain electrical source analysis of laser evoked potentials in response to painful trigeminal nerve stimulation. Electroenceph clin Neurophysiol 95: 14–26PubMedCrossRefGoogle Scholar
  81. 81.
    Valeriani M, Rambaud L, Mauguière F (1996) Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand, Electroencephal clin Neurophysiol 100: 343–353CrossRefGoogle Scholar
  82. 82.
    Garcia-Larrea L (1998) Multimodal approaches to generators of laser evoked potentials: with a little help from our friends. Pain Forum 7: 216–220CrossRefGoogle Scholar
  83. 83.
    Frot M, Mauguière F (1999) Les réponses operculo-insulaires aux stimulations cutanées nociceptives chez l’Homme. Neurophysiol Clin 29: 401–410PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 2001

Authors and Affiliations

  • L. García-Larrea
  • R. Peyron
  • E. Mauguière
  • B. Laurent

There are no affiliations available

Personalised recommendations