In this study, we systematically investigated fiber demography, based on function and distribution, from the periphery to their destinations in the various central (sub) nuclei in the trigeminal brainstem nuclear sensory complex. Conventional and novel compelling information is provided, demonstrating that the ratio and somatotopy of types A and C sensory fibers at the site of a lesion can elucidate important puzzles in TNP disorders. For instance, we explain how of a major shift in the fibers’ direction and ratio at the level of the trigeminal root entry zone (REZ) influences the pathophysiology of pre- and typical trigeminal neuralgia. As a result, there is a high A/C ratio of oral and peri-oral fibers in the supero-medial region of the REZ, which is mostly susceptible to vascular compression. However, this A/C ratio varies considerably at lower proportions in other areas along the peripheral trigeminal pathway, where an injury (viral, vessel compression, or trauma) can lead to a broader spectrum of fiber involvement and, consequently, pain outcome. In summary, we explain how fiber demography can influence pain quality, location, temporal features, progress, and treatment prognosis of TNP in those patients who develop it.
ArvinAMGershonAA (2000). Varicella-zoster virus: virology and clinical management. Cambridge, UK: Cambridge University Press.
2.
AzeradJWodaAAlbe-FessardD (1982). Physiological-properties of neurons in different parts of the cat trigeminal sensory complex. Brain Res246:7-21.
3.
BaeYCOhJMHwangSJShigenagaYValtschanoffJG (2004). Expression of vanilloid receptor TRPV1 in the rat trigeminal sensory nuclei. J Comp Neurol478:62-71.
4.
BoerAHerderNBlodorn-SchlichtNFalkT (2006). Herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive!Am J Dermatopathol28:181-186.
5.
BorsookDDaSilvaAFPloghausABecerraL (2003). Specific and somatotopic functional magnetic resonance imaging activation in the trigeminal ganglion by brush and noxious heat. J Neurosci23:7897-7903.
6.
BrotonJGRosenfeldJP (1982). Rostral trigeminal projections signal perioral facial-pain. Brain Res243:395-400.
7.
BullittETewJMBoydJ (1986). Intracranial tumors in patients with facial-pain. J Neurosurg64:865-871.
8.
CostiganMScholzJWoolfCJ (2009). Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci32:1-32.
9.
CrissmanRSSodemanTDentonAMWardenRJSicilianoDARhoadesRW (1996). Organization of primary afferent axons in the trigeminal sensory root and tract of the rat. J Comp Neurol364:169-183.
10.
CruccuGLeandriMIannettiGDMasciaARomanielloATruiniA. (2001). Small-fiber dysfunction in trigeminal neuralgia: carbamazepine effect on laser-evoked potentials. Neurology56:1722-1726.
11.
CusickJF (1981). Atypical trigeminal neuralgia. J Am Med Assoc245:2328-2329.
12.
DallelRRaboissonPAuroyPWodaA (1987). Participation of the rostral portion of the spinal nucleus of the trigeminal sensory complex in nociception. C R Acad Sci III304:269-274.
13.
DallelRRaboissonPAuroyPWodaA (1988). The rostral part of the trigeminal sensory complex is involved in orofacial nociception. Brain Res448:7-19.
14.
DallelRRaboissonPWodaASessleBJ (1990). Properties of nociceptive and nonnociceptive neurons in trigeminal subnucleus oralis of the rat. Brain Res521:95-106.
15.
DallelRVillanuevaLWodaAVoisinD (2003). Neurobiology of trigeminal pain. Med Sci (Paris)19:567-574.
16.
DandyWE (1934). Concerning the cause of trigeminal neuralgia. Am J Surg24:447-455.
17.
DaSilvaAF (2002). Somatotopic activation in the human trigeminal pain pathway. Boston, MA: Harvard University.
DaSilvaAFBecerraLMakrisNStrassmanAGonzalezRGeatrakisN. (2002). Somatotopic activation in the human trigeminal pain pathway. J Neurosci22:8183-8192.
20.
de LeeuwR, American Academy of Orofacial Pain (2008). Orofacial pain: guidelines for assessment, diagnosis, and management. Chicago, IL: Quintessence.
21.
DelaneyAColvinLAFallonMTDalzielRGMitchellRFleetwood-WalkerSM (2009). Postherpetic neuralgia: from preclinical models to the clinic. Neurotherapeutics6:630-637.
22.
DevorM (2009). Ectopic discharge in Abeta afferents as a source of neuropathic pain. Exp Brain Res196:115-128.
23.
DevorMAmirRRappaportZH (2002a). Pathophysiology of trigeminal neuralgia: the ignition hypothesis. Clin J Pain18:4-13.
24.
DevorMGovrin-LippmannRRappaportZH (2002b). Mechanism of trigeminal neuralgia: an ultrastructural analysis of trigeminal root specimens obtained during microvascular decompression surgery. J Neurosurg96:532-543.
25.
DualeCLuccariniPCadetRWodaA (1996). Effects of morphine microinjections into the trigeminal sensory complex on the formalin test in the rat. Exp Neurol142:331-339.
26.
DworkinRHGnannJWOaklanderALRajaSNSchmaderKEWhitleyRJ (2008). Diagnosis and assessment of pain associated with herpes zoster and postherpetic neuralgia. J Pain9(Suppl 1):37-44.
27.
EllerJLRaslanAMBurchielKJ (2005). Trigeminal neuralgia: definition and classification. Neurosurg Focus18:E3.
FiladoraVA2ndSistTCLemaMJ (1999). Acute herpetic neuralgia and postherpetic neuralgia in the head and neck: response to gabapentin in five cases. Reg Anesth Pain Med24:170-174.
FujiwaraSSasakiMWadaTKudoKHirookaRIshigakiD. (2010). High-resolution diffusion tensor imaging for the detection of diffusion abnormalities in the trigeminal nerves of patients with trigeminal neuralgia caused by neurovascular compression. J Neuroimaging21: e102-e108.
32.
Grigoryan YuASlavinKVOgleznevK (1994). Ultrasonic lesion of the trigeminal nucleus caudalis for deafferentation facial pain. Acta Neurochir (Wien)131:229-235.
33.
Hope-SimpsonRE (1965). The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Soc Med58:9-20.
34.
HoshiyamaMKakigiR (2000). After-effect of transcutaneous electrical nerve stimulation (TENS) on pain-related evoked potentials and magnetic fields in normal subjects. Clin Neurophysiol111:717-724.
35.
HusseinMWilsonLAIllingworthR (1982). Patterns of sensory loss following fractional posterior-fossa Vth nerve-section for trigeminal neuralgia. J Neurol Neurosurg Psychiatry45:786-790.
36.
IwasakiTMurakiRKasaharaTSatoYSataTKurataT (2001). Pathway of viral spread in herpes zoster: detection of the protein encoded by open reading frame 63 of varicella-zoster virus in biopsy specimens. Arch Virol (Suppl 17):109-119.
37.
KennedyPGSteinerI (1994). A molecular and cellular model to explain the differences in reactivation from latency by herpes simplex and varicella-zoster viruses. Neuropathol Appl Neurobiol20:368-374.
38.
KobayashiYMatsumuraG (1996). Central projections of primary afferent fibers from the rat trigeminal nerve labeled with isolectin B4-HRP. Neurosci Lett217:89-92.
39.
KwanCLHuJWSessleBJ (1993). Effects of tooth pulp deafferentation on brainstem neurons of the rat trigeminal subnucleus oralis. Somatosens Mot Res10:115-131.
40.
LoveSGradidgeTCoakhamHB (2001). Trigeminal neuralgia due to multiple sclerosis: ultrastructural findings in trigeminal rhizotomy specimens. Neuropathol Appl Neurobiol27:238-244.
41.
LuccariniPCadetRDualeCWodaA (1998). Effects of’ lesions in the trigeminal oralis and caudalis subnuclei on different orofacial nociceptive responses in the rat. Brain Res803:79-85.
42.
LutzJLinnJMehrkensJHThonNStahlRSeelosK. (2011). Trigeminal neuralgia due to neurovascular compression: high-spatial-resolution diffusion-tensor imaging reveals microstructural neural changes. Radiology258:524-530.
43.
MaihofnerCNeundorferBStefanHHandwerkerHO (2003). Cortical processing of brush-evoked allodynia. Neuroreport14:785-789.
44.
MarinkovicSGiboHTodorovicVAnticBKovacevicDMilisavljevicM. (2009). Ultrastructure and immunohistochemistry of the trigeminal peripheral myelinated axons in patients with neuralgia. Clin Neurol Neurosurg111:795-800.
45.
MillerJPAcarFHamiltonBEBurchielKJ (2009). Radiographic evaluation of trigeminal neurovascular compression in patients with and without trigeminal neuralgia. Clinical article. J Neurosurg110: 627-632.
MurakiRIwasakiTSataTSatoYKurataT (1996). Hair follicle involvement in herpes zoster: pathway of viral spread from ganglia to skin. Virchows Arch428:275-280.
48.
NahraHPlaghkiL (2003). Modulation of perception and neurophysiological correlates of brief CO2 laser stimuli in humans using concurrent large fiber stimulation. Somatosens Mot Res20:139-147.
49.
No Authors Listed (2004). The international classification of headache disorders. 2nd ed.Cephalalgia24(Suppl 1):9-160.
50.
NomuraTIkezakiKMatsushimaTFukuiM (1994). Trigeminal neuralgia: differentiation between intracranial mass lesions and ordinary vascular compression as causative lesions. Neurosurg Rev17:51-57.
51.
NoordenbosW (1959). Pain: problems pertaining to the transmission of nerve impulses which give rise to pain; preliminary statement. Amsterdam: Elsevier Publ. Co.
52.
OaklanderAL (2001). The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain92:139-145.
53.
OaklanderAL (2008). Mechanisms of pain and itch caused by herpes zoster (shingles). J Pain9(Suppl 1):10-18.
54.
ObermannMYoonMSEseDMaschkeMKaubeHDienerHC. (2007). Impaired trigeminal nociceptive processing in patients with trigeminal neuralgia. Neurology69:835-841.
55.
PajotJPelissierTSierraltaFRaboissonPDallelR (2000). Differential effects of trigeminal tractotomy on A delta- and C-fiber-mediated nociceptive responses. Brain Res863:289-292.
56.
PaxinosGHuangXF (1995). Atlas of the human brainstem. San Diego, CA: Academic Press.
57.
PaxinosGMaiJK, editors (2004). The human nervous system. 3rd ed.San Diego, CA: Elsevier Academic Press.
58.
RoskiRAHorwitzSJSpetzlerRF (1982). Atypical trigeminal neuralgia in a 6-year-old boy. Case report. J Neurosurg56:424-425.
59.
RowbothamMCYosipovitchGConnollyMKFinlayDFordeGFieldsHL (1996). Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis3:205-214.
SekulaRFFredericksonAMJannettaPJBhatiaSQuigleyMRAbdel AzizKM (2009). Microvascular decompression in patients with isolated maxillary division trigeminal neuralgia, with particular attention to venous pathology. Neurosurg Focus27:E10.
63.
SessleBJ (2000). Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med11:57-91.
64.
ShanklandWE (2000). The trigeminal nerve. Part I: An over-view. Cranio18:238-248.
65.
ShanklandWE2nd (2009). Atypical trigeminal neuralgia of the mental nerve: a case study. Cranio27:19-23.
66.
ShigenagaYChenICSuemuneSNishimoriTNasutionIDYoshidaA. (1986a). Oral and facial representation within the medullary and upper cervical dorsal horns in the cat. J Comp Neurol243:388-408.
67.
ShigenagaYOkamotoTNishimoriTSuemuneSNasutionIDChenIC. (1986b). Oral and facial representation in the trigeminal principal and rostral spinal nuclei of the cat. J Comp Neurol244:1-18.
68.
SindouMHoweidyTAcevedoG (2002). Anatomical observations during microvascular decompression for idiopathic trigeminal neuralgia (with correlations between topography of pain and site of the neurovascular conflict). Prospective study in a series of 579 patients. Acta Neurochir (Wein)144:1-13.
69.
SindouMLestonJHoweidyTDecullierEChapuisF (2006). Micro-vascular decompression for primary Trigeminal Neuralgia (typical or atypical). Long-term effectiveness on pain; prospective study with survival analysis in a consecutive series of 362 patients. Acta Neurochir (Wein)148:1235-1245.
70.
SugimotoTTakemuraMSakaiAIshimaruM (1986). Cell size analysis of trigeminal primary afferent neurons comprizing [sic] individual peripheral branches of the rat mandibular nerve. Exp Neurol93:565-573.
71.
SugimotoTTakemuraMWakisakaS (1988). Cell size analysis of primary neurons innervating the cornea and tooth pulp of the rat. Pain32:375-381.
72.
SugimotoTFujiyoshiYHeYFXiaoCIchikawaH (1997). Trigeminal primary projection to the rat brain stem sensory trigeminal nuclear complex and surrounding structures revealed by anterograde transport of cholera toxin B subunit-conjugated and Bandeiraea simplicifolia isolectin B4-conjugated horseradish peroxidase. Neurosci Res28:361-371.
73.
SymondsC (1949). Facial pain [lecture delivered at the Royal College of Surgeons of England, on March 1, 1949]. Ann R Coll Surg Engl4:206-212.
74.
TakemuraMSugimotoTShigenagaY (1991). Difference in central projection of primary afferents innervating facial and intraoral structures in the rat. Exp Neurol111:324-331.
75.
TancioniFGaetaniPVillaniLZappoliFRodriguezYBaenaR (1995). Neurinoma of the trigeminal root and atypical trigeminal neuralgia: case report and review of the literature. Surg Neurol44:36-42.
76.
TashiroTHigoSMatsuyamaT (1984). Soma size comparison of the trigeminal ganglion cells giving rise to the ascending and descending tracts: a horseradish peroxidase study in the cat. Exp Neurol84:37-46.
77.
TorataniNMoriwakiHHyonBNaritomiH (2008). Isolated hemifacial sensory impairment with onion skin distribution caused by small pontine hemorrhage. Eur Neurol59:192-194.
78.
TranTDMatreDCaseyKL (2008). An inhibitory interaction of human cortical responses to stimuli preferentially exciting Adelta or C fibers. Neuroscience152:798-808.
79.
TruiniAGaleottiFCruccuG (2005). New insight into trigeminal neuralgia. J Headache Pain6:237-239.
80.
TruiniAGaleottiFHaanpaaMZucchiRAlbanesiABiasiottaA. (2008). Pathophysiology of pain in postherpetic neuralgia: a clinical and neurophysiological study. Pain140:405-410.
81.
TurpJCGobettiJP (1996). Trigeminal neuralgia versus atypical facial pain. A review of the literature and case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod81:424-432.
WallPDMcMahonSBKoltzenburgM (2006). Wall and Melzack’s textbook of pain. Philadelphia, PA: Elsevier/Churchill Livingstone.
84.
WalshNBoutilierRGlasgowDShaffelburgM (2005). Exclusive involvement of folliculosebaceous units by herpes: a reflection of early herpes zoster. Am J Dermatopathol27:189-194.
85.
WatanabeISvenssonPArendt-NielsenL (1999). Influence of segmental and extra-segmental conditioning, stimuli on cortical potentials evoked by painful electrical stimulation. Somatosens Mot Res16:243-250.
WatsonCPMorsheadCVan der KooyDDeckJEvansRJ (1988). Post-herpetic neuralgia: post-mortem analysis of a case. Pain34: 129-138.
89.
WeinbergJM (2007). Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol57(6 Suppl):130S-135S.
90.
WindleWF (1926). The distribution and probable significance of unmyelinated nerve fibers in the trigeminal nerve of the cat. J Comp Neurol41:453-477.
91.
WodaA (2003). Pain in the trigeminal system: from orofacial nociception to neural network modeling. J Dent Res82:764-768.
92.
WodaAMolatJLLuccariniP (2001). Low doses of N-methyl-D-aspartate antagonists in superficial laminae of medulla oblongata facilitate wind-up of convergent neurones. Neuroscience107:317-327.
93.
WoolfCJMannionRJ (1999). Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet353:1959-1964.
94.
YoungRFKingRB (1973). Fiber spectrum of trigeminal sensory root of baboon determined by electron-microscopy. J Neurosurg38:65-72.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
