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Philos Trans R Soc Lond B Biol Sci. Jul 29, 1999; 354(1387): 1347–1358.
PMCID: PMC1692633

Pain and functional imaging.


Functional neuroimaging has fundamentally changed our knowledge about the cerebral representation of pain. For the first time it has been possible to delineate the functional anatomy of different aspects of pain in the medial and lateral pain systems in the brain. The rapid developments in imaging methods over the past years have led to a consensus in the description of the central pain responses between different studies and also to a definition of a central pain matrix with specialized subfunctions in man. In the near future we will see studies where a systems perspective allows for a better understanding of the regulatory mechanisms in the higher-order frontal and parietal cortices. Also, pending the development of experimental paradigms, the functional anatomy of the emotional aspects of pain will become better known.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andersson JL, Lilja A, Hartvig P, Långström B, Gordh T, Handwerker H, Torebjörk E. Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography. Exp Brain Res. 1997 Nov;117(2):192–199. [PubMed]
  • Apkarian AV, Shi T. Squirrel monkey lateral thalamus. I. Somatic nociresponsive neurons and their relation to spinothalamic terminals. J Neurosci. 1994 Nov;14(11 Pt 2):6779–6795. [PubMed]
  • Apkarian AV, Stea RA, Manglos SH, Szeverenyi NM, King RB, Thomas FD. Persistent pain inhibits contralateral somatosensory cortical activity in humans. Neurosci Lett. 1992 Jun 22;140(2):141–147. [PubMed]
  • Aziz Q, Andersson JL, Valind S, Sundin A, Hamdy S, Jones AK, Foster ER, Långström B, Thompson DG. Identification of human brain loci processing esophageal sensation using positron emission tomography. Gastroenterology. 1997 Jul;113(1):50–59. [PubMed]
  • Babiloni F, Babiloni C, Carducci F, Del Gaudio M, Onorati P, Urbano A. A high resolution EEG method based on the correction of the surface Laplacian estimate for the subject's variable scalp thickness. Electroencephalogr Clin Neurophysiol. 1997 Oct;103(4):486–492. [PubMed]
  • Bandler R, Shipley MT. Columnar organization in the midbrain periaqueductal gray: modules for emotional expression? Trends Neurosci. 1994 Sep;17(9):379–389. [PubMed]
  • Bench CJ, Friston KJ, Brown RG, Scott LC, Frackowiak RS, Dolan RJ. The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression. Psychol Med. 1992 Aug;22(3):607–615. [PubMed]
  • Brewer JB, Zhao Z, Desmond JE, Glover GH, Gabrieli JD. Making memories: brain activity that predicts how well visual experience will be remembered. Science. 1998 Aug 21;281(5380):1185–1187. [PubMed]
  • Brüggemann J, Shi T, Apkarian AV. Squirrel monkey lateral thalamus. II. Viscerosomatic convergent representation of urinary bladder, colon, and esophagus. J Neurosci. 1994 Nov;14(11 Pt 2):6796–6814. [PubMed]
  • Buckner RL, Koutstaal W, Schacter DL, Dale AM, Rotte M, Rosen BR. Functional-anatomic study of episodic retrieval. II. Selective averaging of event-related fMRI trials to test the retrieval success hypothesis. Neuroimage. 1998 Apr;7(3):163–175. [PubMed]
  • Casey KL, Minoshima S, Berger KL, Koeppe RA, Morrow TJ, Frey KA. Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli. J Neurophysiol. 1994 Feb;71(2):802–807. [PubMed]
  • 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 Jul;76(1):571–581. [PubMed]
  • Chudler EH, Anton F, Dubner R, Kenshalo DR., Jr Responses of nociceptive SI neurons in monkeys and pain sensation in humans elicited by noxious thermal stimulation: effect of interstimulus interval. J Neurophysiol. 1990 Mar;63(3):559–569. [PubMed]
  • Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, Duncan GH. Distributed processing of pain and vibration by the human brain. J Neurosci. 1994 Jul;14(7):4095–4108. [PubMed]
  • Corbetta M, Miezin FM, Shulman GL, Petersen SE. Selective attention modulates extrastriate visual regions in humans during visual feature discrimination and recognition. Ciba Found Symp. 1991;163:165–180. [PubMed]
  • Corfield DR, Fink GR, Ramsay SC, Murphy K, Harty HR, Watson JD, Adams L, Frackowiak RS, Guz A. Evidence for limbic system activation during CO2-stimulated breathing in man. J Physiol. 1995 Oct 1;488(Pt 1):77–84. [PMC free article] [PubMed]
  • Craig AD, Bushnell MC, Zhang ET, Blomqvist A. A thalamic nucleus specific for pain and temperature sensation. Nature. 1994 Dec 22;372(6508):770–773. [PubMed]
  • Craig AD, Reiman EM, Evans A, Bushnell MC. Functional imaging of an illusion of pain. Nature. 1996 Nov 21;384(6606):258–260. [PubMed]
  • Davis KD, Taylor SJ, Crawley AP, Wood ML, Mikulis DJ. Functional MRI of pain- and attention-related activations in the human cingulate cortex. J Neurophysiol. 1997 Jun;77(6):3370–3380. [PubMed]
  • Deiber MP, Passingham RE, Colebatch JG, Friston KJ, Nixon PD, Frackowiak RS. Cortical areas and the selection of movement: a study with positron emission tomography. Exp Brain Res. 1991;84(2):393–402. [PubMed]
  • Derbyshire SW, Jones AK, Devani P, Friston KJ, Feinmann C, Harris M, Pearce S, Watson JD, Frackowiak RS. Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography. J Neurol Neurosurg Psychiatry. 1994 Oct;57(10):1166–1172. [PMC free article] [PubMed]
  • Derbyshire SW, Vogt BA, Jones AK. Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex. Exp Brain Res. 1998 Jan;118(1):52–60. [PubMed]
  • Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behaviour. Brain. 1995 Feb;118(Pt 1):279–306. [PubMed]
  • Di Piero V, Ferracuti S, Sabatini U, Pantano P, Cruccu G, Lenzi GL. A cerebral blood flow study on tonic pain activation in man. Pain. 1994 Feb;56(2):167–173. [PubMed]
  • Di Piero V, Fiacco F, Tombari D, Pantano P. Tonic pain: a SPET study in normal subjects and cluster headache patients. Pain. 1997 Apr;70(2-3):185–191. [PubMed]
  • Disbrow E, Buonocore M, Antognini J, Carstens E, Rowley HA. Somatosensory cortex: a comparison of the response to noxious thermal, mechanical, and electrical stimuli using functional magnetic resonance imaging. Hum Brain Mapp. 1998;6(3):150–159. [PubMed]
  • Dong WK, Salonen LD, Kawakami Y, Shiwaku T, Kaukoranta EM, Martin RF. Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkeys. Brain Res. 1989 Apr 10;484(1-2):314–324. [PubMed]
  • Drevets WC, Burton H, Videen TO, Snyder AZ, Simpson JR, Jr, Raichle ME. Blood flow changes in human somatosensory cortex during anticipated stimulation. Nature. 1995 Jan 19;373(6511):249–252. [PubMed]
  • Fox PT, Mintun MA. Noninvasive functional brain mapping by change-distribution analysis of averaged PET images of H215O tissue activity. J Nucl Med. 1989 Feb;30(2):141–149. [PubMed]
  • Fox PT, Raichle ME. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1140–1144. [PMC free article] [PubMed]
  • Freund TF, Antal M. GABA-containing neurons in the septum control inhibitory interneurons in the hippocampus. Nature. 1988 Nov 10;336(6195):170–173. [PubMed]
  • Friberg L, Olesen J, Lassen NA, Olsen TS, Karle A. Cerebral oxygen extraction, oxygen consumption, and regional cerebral blood flow during the aura phase of migraine. Stroke. 1994 May;25(5):974–979. [PubMed]
  • Friston KJ, Fletcher P, Josephs O, Holmes A, Rugg MD, Turner R. Event-related fMRI: characterizing differential responses. Neuroimage. 1998 Jan;7(1):30–40. [PubMed]
  • Friston KJ, Josephs O, Rees G, Turner R. Nonlinear event-related responses in fMRI. Magn Reson Med. 1998 Jan;39(1):41–52. [PubMed]
  • Friston KJ, Frith CD, Liddle PF, Dolan RJ, Lammertsma AA, Frackowiak RS. The relationship between global and local changes in PET scans. J Cereb Blood Flow Metab. 1990 Jul;10(4):458–466. [PubMed]
  • Friston KJ, Price CJ, Fletcher P, Moore C, Frackowiak RS, Dolan RJ. The trouble with cognitive subtraction. Neuroimage. 1996 Oct;4(2):97–104. [PubMed]
  • Fukushima T, Ikeda T, Uyama E, Uchino M, Okabe H, Ando M. Cognitive event-related potentials and brain magnetic resonance imaging in HTLV-1 associated myelopathy (HAM). J Neurol Sci. 1994 Oct;126(1):30–39. [PubMed]
  • Ghatan PH, Hsieh JC, Wirsén-Meurling A, Wredling R, Eriksson L, Stone-Elander S, Levander S, Ingvar M. Brain activation induced by the perceptual maze test: a PET study of cognitive performance. Neuroimage. 1995 Jun;2(2):112–124. [PubMed]
  • Ghatan PH, Hsieh JC, Petersson KM, Stone-Elander S, Ingvar M. Coexistence of attention-based facilitation and inhibition in the human cortex. Neuroimage. 1998 Jan;7(1):23–29. [PubMed]
  • Grafton ST, Mazziotta JC, Woods RP, Phelps ME. Human functional anatomy of visually guided finger movements. Brain. 1992 Apr;115(Pt 2):565–587. [PubMed]
  • Greenspan JD, Winfield JA. Reversible pain and tactile deficits associated with a cerebral tumor compressing the posterior insula and parietal operculum. Pain. 1992 Jul;50(1):29–39. [PubMed]
  • Gyulai FE, Firestone LL, Mintun MA, Winter PM. In vivo imaging of nitrous oxide-induced changes in cerebral activation during noxious heat stimuli. Anesthesiology. 1997 Mar;86(3):538–548. [PubMed]
  • Hachinski VC, Olesen J, Norris JW, Larsen B, Enevoldsen E, Lassen NA. Cerebral hemodynamics in migraine. Can J Neurol Sci. 1977 Nov;4(4):245–249. [PubMed]
  • Hari R, Kaukoranta E. Neuromagnetic studies of somatosensory system: principles and examples. Prog Neurobiol. 1985;24(3):233–256. [PubMed]
  • Hari R, Portin K, Kettenmann B, Jousmäki V, Kobal G. Right-hemisphere preponderance of responses to painful CO2 stimulation of the human nasal mucosa. Pain. 1997 Aug;72(1-2):145–151. [PubMed]
  • Haxby JV, Horwitz B, Ungerleider LG, Maisog JM, Pietrini P, Grady CL. The functional organization of human extrastriate cortex: a PET-rCBF study of selective attention to faces and locations. J Neurosci. 1994 Nov;14(11 Pt 1):6336–6353. [PubMed]
  • Hsieh JC, Hägermark O, Ståhle-Bäckdahl M, Ericson K, Eriksson L, Stone-Elander S, Ingvar M. Urge to scratch represented in the human cerebral cortex during itch. J Neurophysiol. 1994 Dec;72(6):3004–3008. [PubMed]
  • Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M. Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain. 1995 Nov;63(2):225–236. [PubMed]
  • Hsieh JC, Hannerz J, Ingvar M. Right-lateralised central processing for pain of nitroglycerin-induced cluster headache. Pain. 1996 Sep;67(1):59–68. [PubMed]
  • Hsieh JC, Ståhle-Bäckdahl M, Hägermark 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 Feb;64(2):303–314. [PubMed]
  • Huttunen J, Kobal G, Kaukoranta E, Hari R. Cortical responses to painful CO2 stimulation of nasal mucosa; a magnetoencephalographic study in man. Electroencephalogr Clin Neurophysiol. 1986 Oct;64(4):347–349. [PubMed]
  • Iadarola MJ, Max MB, Berman KF, Byas-Smith MG, Coghill RC, Gracely RH, Bennett GJ. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain. 1995 Oct;63(1):55–64. [PubMed]
  • Iadarola MJ, Berman KF, Zeffiro TA, Byas-Smith MG, Gracely RH, Max MB, Bennett GJ. Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. Brain. 1998 May;121(Pt 5):931–947. [PubMed]
  • Ingvar DH. "Memory of the future": an essay on the temporal organization of conscious awareness. Hum Neurobiol. 1985;4(3):127–136. [PubMed]
  • Ingvar M, Eriksson L, Greitz T, Stone-Elander S, Dahlbom M, Rosenqvist G, af Trampe P, von Euler C. Methodological aspects of brain activation studies: cerebral blood flow determined with [15O]butanol and positron emission tomography. J Cereb Blood Flow Metab. 1994 Jul;14(4):628–638. [PubMed]
  • Ito M. Movement and thought: identical control mechanisms by the cerebellum. Trends Neurosci. 1993 Nov;16(11):448–454. [PubMed]
  • Jenkins IH, Brooks DJ, Nixon PD, Frackowiak RS, Passingham RE. Motor sequence learning: a study with positron emission tomography. J Neurosci. 1994 Jun;14(6):3775–3790. [PubMed]
  • Jones AK, Brown WD, Friston KJ, Qi LY, Frackowiak RS. Cortical and subcortical localization of response to pain in man using positron emission tomography. Proc Biol Sci. 1991 Apr 22;244(1309):39–44. [PubMed]
  • Jones AK, Liyi Q, Cunningham VV, Brown DW, Ha-Kawa S, Fujiwara T, Friston KF, Silva S, Luthra SK, Jones T. Endogenous opiate response to pain in rheumatoid arthritis and cortical and subcortical response to pain in normal volunteers using positron emission tomography. Int J Clin Pharmacol Res. 1991;11(6):261–266. [PubMed]
  • Jones AK, Cunningham VJ, Ha-Kawa S, Fujiwara T, Luthra SK, Silva S, Derbyshire S, Jones T. Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis. Br J Rheumatol. 1994 Oct;33(10):909–916. [PubMed]
  • Jones AP, Hughes DG, Brettle DS, Robinson L, Sykes JR, Aziz Q, Hamdy S, Thompson DG, Derbyshire SW, Chen AC, et al. Experiences with functional magnetic resonance imaging at 1 tesla. Br J Radiol. 1998 Feb;71(842):160–166. [PubMed]
  • Kakigi R, Koyama S, Hoshiyama M, Kitamura Y, Shimojo M, Watanabe S. Pain-related magnetic fields following painful CO2 laser stimulation in man. Neurosci Lett. 1995 Jun 2;192(1):45–48. [PubMed]
  • Kenshalo DR, Jr, Chudler EH, Anton F, Dubner R. SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation. Brain Res. 1988 Jun 28;454(1-2):378–382. [PubMed]
  • Lassen NA. Neuroreceptor quantitation in vivo by the steady-state principle using constant infusion or bolus injection of radioactive tracers. J Cereb Blood Flow Metab. 1992 Sep;12(5):709–716. [PubMed]
  • May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet. 1998 Jul 25;352(9124):275–278. [PubMed]
  • May A, Kaube H, Büchel C, Eichten C, Rijntjes M, Jüptner M, Weiller C, Diener HC. Experimental cranial pain elicited by capsaicin: a PET study. Pain. 1998 Jan;74(1):61–66. [PubMed]
  • Menon RS, Ogawa S, Tank DW, Uğurbil K. Tesla gradient recalled echo characteristics of photic stimulation-induced signal changes in the human primary visual cortex. Magn Reson Med. 1993 Sep;30(3):380–386. [PubMed]
  • Menon V, Ford JM, Lim KO, Glover GH, Pfefferbaum A. Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection. Neuroreport. 1997 Sep 29;8(14):3029–3037. [PubMed]
  • Olesen J, Friberg L, Olsen TS, Iversen HK, Lassen NA, Andersen AR, Karle A. Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol. 1990 Dec;28(6):791–798. [PubMed]
  • Pardo JV, Pardo PJ, Janer KW, Raichle ME. The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm. Proc Natl Acad Sci U S A. 1990 Jan;87(1):256–259. [PMC free article] [PubMed]
  • Paus T, Petrides M, Evans AC, Meyer E. Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study. J Neurophysiol. 1993 Aug;70(2):453–469. [PubMed]
  • Petersson KM, Elfgren C, Ingvar M. A dynamic role of the medial temporal lobe during retrieval of declarative memory in man. Neuroimage. 1997 Jul;6(1):1–11. [PubMed]
  • Peyron R, García-Larrea L, Grégoire MC, Convers P, Lavenne F, Veyre L, Froment JC, Mauguière F, Michel D, Laurent B. Allodynia after lateral-medullary (Wallenberg) infarct. A PET study. Brain. 1998 Feb;121(Pt 2):345–356. [PubMed]
  • Price CJ, Friston KJ. Cognitive conjunction: a new approach to brain activation experiments. Neuroimage. 1997 May;5(4 Pt 1):261–270. [PubMed]
  • Raichle ME. Food for thought. The metabolic and circulatory requirements of cognition. Ann N Y Acad Sci. 1997 Dec 19;835:373–385. [PubMed]
  • Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997 Aug 15;277(5328):968–971. [PubMed]
  • Roland P. Cortical representation of pain. Trends Neurosci. 1992 Jan;15(1):3–5. [PubMed]
  • Duncan GH, Bushnell MC, Talbot JD, Evans AC, Meyer E, Marrett S. Pain and activation in the thalamus. Trends Neurosci. 1992 Jul;15(7):252–253. [PubMed]
  • Rosen BR, Buckner RL, Dale AM. Event-related functional MRI: past, present, and future. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):773–780. [PMC free article] [PubMed]
  • Rosen SD, Paulesu E, Frith CD, Frackowiak RS, Davies GJ, Jones T, Camici PG. Central nervous pathways mediating angina pectoris. Lancet. 1994 Jul 16;344(8916):147–150. [PubMed]
  • Rösler F, Heil M, Hennighausen E. Exploring memory functions by means of brain electrical topography: a review. Brain Topogr. 1995 Summer;7(4):301–313. [PubMed]
  • Schad LR, Wiener E, Baudendistel KT, Müller E, Lorenz WJ. Event-related functional MR imaging of visual cortex stimulation at high temporal resolution using a standard 1.5 T imager. Magn Reson Imaging. 1995;13(6):899–901. [PubMed]
  • Seitz RJ, Roland PE. Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study. Acta Neurol Scand. 1992 Jul;86(1):60–67. [PubMed]
  • Shallice T. Specific impairments of planning. Philos Trans R Soc Lond B Biol Sci. 1982 Jun 25;298(1089):199–209. [PubMed]
  • Shulman GL, Corbetta M, Buckner RL, Raichle ME, Fiez JA, Miezin FM, Petersen SE. Top-down modulation of early sensory cortex. Cereb Cortex. 1997 Apr-May;7(3):193–206. [PubMed]
  • Snow PJ, Lumb BM, Cervero F. The representation of prolonged and intense, noxious somatic and visceral stimuli in the ventrolateral orbital cortex of the cat. Pain. 1992 Jan;48(1):89–99. [PubMed]
  • Talbot JD, Marrett S, Evans AC, Meyer E, Bushnell MC, Duncan GH. Multiple representations of pain in human cerebral cortex. Science. 1991 Mar 15;251(4999):1355–1358. [PubMed]
  • Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, Duncan GH. Distributed processing of pain and vibration by the human brain. J Neurosci. 1994 Jul;14(7):4095–4108. [PubMed]
  • Tarkka IM, Stokić DS, Basile LF, Papanicolaou AC. Electric source localization of the auditory P300 agrees with magnetic source localization. Electroencephalogr Clin Neurophysiol. 1995 Nov;96(6):538–545. [PubMed]
  • Thatcher RW. Tomographic electroencephalography/magnetoencephalography. Dynamics of human neural network switching. J Neuroimaging. 1995 Jan;5(1):35–45. [PubMed]
  • Thierry AM, Godbout R, Mantz J, Glowinski J. Influence of the ascending monoaminergic systems on the activity of the rat prefrontal cortex. Prog Brain Res. 1990;85:357–365. [PubMed]
  • Tseng GF, Haberly LB. Characterization of synaptically mediated fast and slow inhibitory processes in piriform cortex in an in vitro slice preparation. J Neurophysiol. 1988 May;59(5):1352–1376. [PubMed]
  • Vaccarino AL, Melzack R. Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain. 1989 Nov;39(2):213–219. [PubMed]
  • Vogt BA, Derbyshire S, Jones AK. Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging. Eur J Neurosci. 1996 Jul;8(7):1461–1473. [PubMed]
  • Weiller C, May A, Limmroth V, Jüptner M, Kaube H, Schayck RV, Coenen HH, Diener HC. Brain stem activation in spontaneous human migraine attacks. Nat Med. 1995 Jul;1(7):658–660. [PubMed]
  • Young GB, Blume WT. Painful epileptic seizures. Brain. 1983 Sep;106(Pt 3):537–554. [PubMed]

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