title: The representation of experimental tooth pain from upper and lower jaws in the human trigeminal pathway.
abstract: FMRI was used to study the differences of cerebral processing of nociceptive input from the 2nd and the 3rd branches of the trigeminal nerve by electrical stimulation of the tooth pulps of the upper and lower canines. The focus of the study was an investigation of the different levels of the trigeminal system in brainstem, thalamus and in cortical regions which are known to be involved in pain processing. Increased blood oxygen level dependency (BOLD) signals were found ipsilaterally in the trigeminal ganglion and the spinal nucleus (SpV) of the trigeminal nerve. SpV-related activations showed some somatotopic organization. Bilateral activation was found in the structures of the antinociceptive system in the midbrain. Contralateral activations were encountered at the level of the pons. In the thalamus ipsilateral activations were found in the ventral parts. Bilateral activation occurred in the medial dorsal nuclei. At the cortical level BOLD activations were encountered bilaterally in the primary somatosensory cortex (S1, lateral pain system), the cingulate and insular cortex (medial pain system). In the cortex a small difference in the representation of the two trigeminal branches was detected only in S1 on both hemispheres. These findings demonstrate that trigeminal pain markedly activates the lateral and medial pain projection systems and the majority of the affected brain regions showed no difference regarding the input from lower or upper tooth. This lack of discrimination may explain why sometimes it is difficult for patients to locate the exact source of the intraoral clinical pain conditions.
authors.affiliation: Department of Physiology and Pathophysiology, University of Erlangen-Nuernberg, Germany Institute of Dentistry, University of Turku, and Dept. of Oral and Maxillofacial Diseases, Turku University Central Hospital (TUCH), Finland Department of Neuroradiology, University of Erlangen-Nuernberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Weigelt
authors.forename: P
authors.initials: P
authors.lastname: Terekhin
authors.forename: P
authors.initials: P
authors.lastname: Kemppainen
authors.forename: A
authors.initials: A
authors.lastname: Dörfler
authors.forename: C
authors.initials: C
authors.lastname: Forster
mesh_terms: D000328:Adult; D000344:Afferent Pathways / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods*; D004558:Electric Stimulation; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D008334:Mandible / Q000294:innervation* / Q000503:physiopathology; D008437:Maxilla / Q000294:innervation* / Q000503:physiopathology; D010147:Pain Measurement; D014070:Tooth / Q000294:innervation* / Q000503:physiopathology; D014098:Toothache / Q000209:etiology / Q000503:physiopathology*; D012668:Trigeminal Ganglion / Q000503:physiopathology; D014276:Trigeminal Nerve / Q000503:physiopathology*; D055815:Young Adult
references.citation: Andersson JL, Lilja A, Hartvig P, Langstrom B, Gordh T, Handwerker H, Torebjork E. Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography. Exp Brain Res. 1997;117:192-199.
references.citation: Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463-484.
references.citation: 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;99:313-321.
references.citation: Biswal B, DeYoe AE, Hyde JS. Reduction of physiological fluctuations in fMRI using digital filters. Magn Reson Med. 1996;35:107-113.
references.citation: Borsook D, DaSilva AF, Ploghaus A, Becerra L. Specific and somatotopic functional magnetic resonance imaging activation in the trigeminal ganglion by brush and noxious heat. J Neurosci. 2003;23:7897-7903.
references.citation: Buchel C, Bornhovd K, Quante M, Glauche V, Bromm B, Weiller C. 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. 2002;22:970-976.
references.citation: Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci. 2000;4:215-222.
references.citation: Byers MR, Narhi MV. Dental injury models: experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions. Crit Rev Oral Biol Med. 1999;10:4-39.
references.citation: Craig AD. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol. 2003;13:500-505.
references.citation: DaSilva AF, Becerra L, Makris N, Strassman AM, Gonzalez RG, Geatrakis N, Borsook D. Somatotopic activation in the human trigeminal pain pathway. J Neurosci. 2002;22:8183-8192.
references.citation: DaSilva AF, Becerra L, Pendse G, Chizh B, Tully S, Borsook D. Colocalized structural and functional changes in the cortex of patients with trigeminal neuropathic pain. PLoS One. 2008;3:e3396.
references.citation: 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;484:314-324.
references.citation: Eberhardt M, Hoffmann T, Sauer SK, Messlinger K, Reeh PW, Fischer MJ. Calcitonin gene-related peptide release from intact isolated dorsal root and trigeminal ganglia. Neuropeptides. 2008;42:311-317.
references.citation: Ellrich J. Brain stem reflexes: probing human trigeminal nociception. News Physiol Sci. 2000;15:94-97.
references.citation: Ettlin DA, Zhang H, Lutz K, Jarmann T, Meier D, Gallo LM, Jancke L, Palla S. Cortical activation resulting from painless vibrotactile dental stimulation measured by functional magnetic resonance imaging (FMRI). J Dent Res. 2004;83:757-761.
references.citation: Gelnar PA, Krauss BR, Szeverenyi NM, Apkarian AV. Fingertip representation in the human somatosensory cortex: an fMRI study. NeuroImage. 1998;7:261-283.
references.citation: Glover GH, Li TQ, Ress D. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med. 2000;44:162-167.
references.citation: Huang LY, Neher E. Ca(2+)-dependent exocytosis in the somata of dorsal root ganglion neurons. Neuron. 1996;17:135-145.
references.citation: Iannetti GD, Porro CA, Pantano P, Romanelli PL, Galeotti F, Cruccu G. Representation of different trigeminal divisions within the primary and secondary human somatosensory cortex. NeuroImage. 2003;19:906-912.
references.citation: Iannilli E, Del Gratta C, Gerber JC, Romani GL, Hummel T. Trigeminal activation using chemical, electrical, and mechanical stimuli. Pain. 2008;139:376-388.
references.citation: Jantsch HH, Kemppainen P, Ringler R, Handwerker HO, Forster C. Cortical representation of experimental tooth pain in humans. Pain. 2005;118:390-399.
references.citation: Kemppainen P, Pertovaara A, Huopaniemi T, Johansson G, Karonen SL. Modification of dental pain and cutaneous thermal sensitivity by physical exercise in man. Brain Res. 1985;360:33-40.
references.citation: Kemppainen P, Forster C, Handwerker HO. The importance of stimulus site and intensity in differences of pain-induced vascular reflexes in human orofacial regions. Pain. 2001;91:331-338.
references.citation: Logothetis NK, Wandell BA. Interpreting the BOLD signal. Annu Rev Physiol. 2004;66:735-769.
references.citation: Matthews BF, Searle BN. Electrical stimulation of teeth. Pain. 1976;2:245-251.
references.citation: Mohr C, Binkofski F, Erdmann C, Buchel C, Helmchen C. The anterior cingulate cortex contains distinct areas dissociating external from self-administered painful stimulation: a parametric fMRI study. Pain. 2005;114:347-357.
references.citation: Mumford JM, Stanley SJ. Sensations on stimulating the pulps of human teeth, thresholds and tolerance ratio. Pain. 1981;10:391-398.
references.citation: Narhi M, Virtanen A, Huopaniemi T, Hirvonen T. Conduction velocities of single pulp nerve fibre units in the cat. Acta Physiol Scand. 1982;116:209-213.
references.citation: Narhi MV. The characteristics of intradental sensory units and their responses to stimulation. J Dent Res. 1985;64:564-571.
references.citation: Park SJ, Zhang S, Chiang CY, Hu JW, Dostrovsky JO, Sessle BJ. Central sensitization induced in thalamic nociceptive neurons by tooth pulp stimulation is dependent on the functional integrity of trigeminal brainstem subnucleus caudalis but not subnucleus oralis. Brain Res. 2006;1112:134-145.
references.citation: Paulus MP, Stein MB. An insular view of anxiety. Biol Psychiatry. 2006;60:383-387.
references.citation: Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin. 2000;30:263-288.
references.citation: Poncelet BP, Wedeen VJ, Weisskoff RM, Cohen MS. Brain parenchyma motion: measurement with cine echo-planar MR imaging. Radiology. 1992;185:645-651.
references.citation: Porro CA, Cettolo V, Francescato MP, Baraldi P. Temporal and intensity coding of pain in human cortex. J Neurophysiol. 1998;80:3312-3320.
references.citation: Porro CA, Lui F, Facchin P, Maieron M, Baraldi P. Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies. Magn Reson Imaging. 2004;22:1539-1548.
references.citation: Ringler R, Greiner M, Kohlloeffel L, Handwerker HO, Forster C. BOLD effects in different areas of the cerebral cortex during painful mechanical stimulation. Pain. 2003;105:445-453.
references.citation: Ruben J, Schwiemann J, Deuchert M, Meyer R, Krause T, Curio G, Villringer K, Kurth R, Villringer A. Somatotopic organization of human secondary somatosensory cortex. Cereb Cortex. 2001;11:463-473.
references.citation: Schoedel AL, Zimmermann K, Handwerker HO, Forster C. The influence of simultaneous ratings on cortical BOLD effects during painful and non-painful stimulation. Pain. 2008;135:131-141.
references.citation: Sessle BJ. Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med. 2000;11:57-91.
references.citation: Sessle BJ. Peripheral and central mechanisms of orofacial pain and their clinical correlates. Minerva Anestesiol. 2005;71:117-136.
references.citation: Stepniewska I, Sakai ST, Qi HX, Kaas JH. Somatosensory input to the ventrolateral thalamic region in the macaque monkey: potential substrate for parkinsonian tremor. J Comp Neurol. 2003;455:378-395.
references.citation: Suvinen TI FAU – Reade P, Reade PC FAU – Kemppainen P, Kemppainen PF, Kononen MF, Dworkin SF. Review of aetiological concepts of temporomandibular pain disorders: towards a biopsychosocial model for integration of physical disorder factors with psychological and psychosocial illness impact factors. Eur J Pain 2005;9:613–33.
references.citation: Takemura M, Sugiyo S, Moritani M, Kobayashi M, Yonehara N. Mechanisms of orofacial pain control in the central nervous system. Arch Histol Cytol. 2006;69:79-100.
references.citation: Thesen S, Heid O, Mueller E, Schad LR. Prospective acquisition correction for head motion with image-based tracking for real-time fMRI. Magn Reson Med. 2000;44:457-465.
references.citation: Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55:377-391.
references.citation: Treede RD, Kenshalo DR, Gracely RH, Jones AK. The cortical representation of pain. Pain. 1999;79:105-111.
references.citation: Usunoff KG, Marani E, Schoen JH. The trigeminal system in man. Adv Anat Embryol Cell Biol. 1997;136:1-126.
references.citation: van Westen D, Fransson P, Olsrud J, Rosen B, Lundborg G, Larsson EM. Fingersomatotopy in area 3b: an fMRI-study. BMC Neurosci. 2004;5:28.
references.citation: Virtanen AS. Electrical stimulation of pulp nerves – comparison of monopolar and bipolar electrode coupling. Pain. 1985;23:279-288.
references.citation: Virtanen AS, Huopaniemi T, Narhi MV, Pertovaara A, Wallgren K. The effect of temporal parameters on subjective sensations evoked by electrical tooth stimulation. Pain. 1987;30:361-371.
references.citation: Zhang WT, Mainero C, Kumar A, Wiggins CJ, Benner T, Purdon PL, Bolar DS, Kwong KK, Sorensen AG. Strategies for improving the detection of fMRI activation in trigeminal pathways with cardiac gating. NeuroImage. 2006;31:1506-1512.