Trigeminal neuralgia pathogenesis



Many anatomical variants can potentially contribute to trigeminal neuralgia. These include compression by the superior cerebellar artery and less commonly, bony compression near the Meckel's cave.


Banerjee et al. reported the gross and histological findings of a cadaveric specimen found to have a bony roof of the trigeminal cave. During the routine dissection of a male cadaver, an unusual finding of the skull base was observed. Palpation over the porus trigeminus identified a completely ossified roof. The bony spicule was 1.22 cm long and 0.76 mm wide. The trigeminal nerve was noted to have an indented region just below its contact with the ossified roof of the porus trigeminus. No frank nerve degeneration was noted with histological analysis. Normal mature bone tissue was noted surrounded by a sheath of dura mater. Future radiographic research is needed to better elucidate if ossification of the roof of the trigeminal cave is related to clinical symptoms of trigeminal neuralgia (TN). However, physicians should be cognizant of radiographic ossification of the trigeminal cave as a potential cause of TN 1)


The main cause of lightning-like pain in patients with TN may be chronic inflammation that causes nerve demyelination. Nano-silicon (Si) can safely and continuously produce hydrogen in the alkaline environment of the intestine to exert systemic anti-inflammatory effects. Hydrogen has a promising anti-neuroinflammatory impact. The study aimed to determine how intra-intestinal application of a hydrogen-producing Si-based agent affected the demyelination of the trigeminal ganglion in TN rats. We discovered that increased expression of the NLRP3 inflammasome and inflammatory cell infiltration occurred concurrently with demyelination of the trigeminal ganglion in TN rats. We could determine that the neural effect of the hydrogen-producing Si-based agent was connected to the inhibition of microglial pyroptosis by using transmission electron microscopy. The results demonstrated that the Si-based agent reduced the infiltration of inflammatory cells and the degree of neural demyelination. In a subsequent study, it was discovered that hydrogen produced by a Si-based agent regulates the pyroptosis of microglia may through the NLRP3-caspase-1-GSDMD pathway, preventing the development of chronic neuroinflammation and consequently lowering the incidence of nerve demyelination. This study offers a novel strategy for elucidating the pathogenesis of TN and developing potential therapeutic drugs 2)


B cell receptor signaling pathway, cell adhesion, complement and coagulation cascade pathways, neuroimmune pathways are closely related to the occurrence of trigeminal neuralgia. The interaction of multiple genes among Cacna1s, Cox8b, My11, Ckm, Mylpf, Myoz1, Tnnc2 leads to the occurrence of trigeminal neuralgia 3).

see Neurovascular contact in trigeminal neuralgia.

see Superior cerebellar artery aneurysm.

see Tumor associated trigeminal neuralgia.

Other anatomical abnormalities have been considered, including differences of trigeminal nerve (TN) volume.

No correlation between volumetry and clinical data was detected 4).

see Multiple sclerosis related trigeminal neuralgia.

The incidence rates of posterior fossa tumor-induced TN range from 2.1–11.6% percent; in the literature; these cases mainly comprise meningiomas (14–54% percnt;), epidermoid tumors (8–64% percent;), and vestibular schwannomas (7–31% percnt;) 5) 6) 7) 8).


It appears that aggressive bony edges may contribute-at least indirectly-to the neuralgia. This should be considered for surgical indication and conduct of surgery when patients undergo MVD 9).

Abarca et al. data support the theory that a small volume of the posterior fossa cisterns containing the trigeminal nerve may increase the incidence of ITN 10).

Horínek et al. did not find any association between the clinical neurovascular conflict (NVC) and the size of the posterior fossa and its substructures. MRI volumetry may show the atrophy of the affected trigeminal nerve in clinical neuromuscular conflict 11).

Park et al. did not find any volumetric differences (including the cisternal and parenchymal volumes) 12).

Chiari's malformation and hydrocephalus are rare associates of TN. The pathophysiology of TN in these cases may be due to neurovascular conflict, related to raised intracranial pressure from the hydrocephalus and/or the small posterior fossa volume in these patients. Drainage of associated hydrocephalus may be an effective surgical treatment 13).

High-resolution magnetic resonance imaging scans are able to demonstrate significant volumetric differences of the pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may be correlated with the occurrence of a neurovascular compression, and these findings support the neurovascular compression theory in idiopathic TN 14).

Park et al. confirmed that small pontomesencephalic cistern volumes were more frequent in patients with TN 15).


1)
Banerjee S, Iwanaga J, Dumont AS, Tubbs RS. An unusual finding of the Porus trigeminus: Case report with histological findings. Anat Histol Embryol. 2023 Mar 27. doi: 10.1111/ahe.12917. Epub ahead of print. PMID: 36971463.
2)
Mu G, Li Q, Lu B, Yu X. Amelioration of nerve demyelination by hydrogen-producing silicon-based agent in neuropathic pain rats. Int Immunopharmacol. 2023 Mar 16;117:110033. doi: 10.1016/j.intimp.2023.110033. Epub ahead of print. PMID: 36933448.
3)
Liu YM, Chai Y, Wei WB, Liu ZY, Han ZX, Chen MJ. [Analysis of potential pathogenic factors of trigeminal neuralgia in rats]. Shanghai Kou Qiang Yi Xue. 2023 Feb;32(1):33-39. Chinese. PMID: 36973841.
4)
Urgosik D, Keller J, Svehlik V, Pingle M, Horinek D. Trigeminal nerve asymmetry in classic trigeminal neuralgia - pretreatment volumetry and clinical evaluation in patients irradiated by Leksell Gamma Knife. Neuro Endocrinol Lett. 2014 Jul 20;35(4). [Epub ahead of print] PubMed PMID: 25038607.
5)
Barker FG, 2nd, Jannetta PJ, Babu RP, Pomonis S, Bissonette DJ, Jho HD. Long-term outcome after operation for trigeminal neuralgia in patients with posterior fossa tumors. J Neurosurg. 1996;84:818–825.
6)
Jamjoom AB, Jamjoom ZA, al-Fehaily M, el-Watidy S, al-Moallem M, Nain Ur R. Trigeminal neuralgia related to cerebellopontine angle tumors. Neurosurg Rev. 1996;19:237–241.
7)
Nomura T, Ikezaki K, Matsushima T, Fukui M. Trigeminal neuralgia: differentiation between intracranial mass lesions and ordinary vascular compression as causative lesions. Neurosurg Rev. 1994;17:51–57.
8)
Shulev Y, Trashin A, Gordienko K. Secondary trigeminal neuralgia in cerebellopontine angle tumors. Skull Base. 2011;21:287–294
9)
Brinzeu A, Dumot C, Sindou M. Role of the petrous ridge and angulation of the trigeminal nerve in the pathogenesis of trigeminal neuralgia, with implications for microvascular decompression. Acta Neurochir (Wien). 2018 Jan 20. doi: 10.1007/s00701-018-3468-1. [Epub ahead of print] PubMed PMID: 29353407.
10)
Abarca-Olivas J, Feliu-Rey E, Sempere AP, Sanchez-Payá J, Baño-Ruiz E, Caminero-Canas MA, Nieto-Navarro J, Botella-Asunción C. [Volumetric measurement of the posterior fossa and its components using magnetic resonance imaging in idiopathic trigeminal neuralgia]. Rev Neurol. 2010 Nov 1;51(9):520-4. Spanish. PubMed PMID: 20979031.
11)
Horínek D, Brezová V, Nimsky C, Belsan T, Martinkovic L, Masopust V, Vrána J, Kozler P, Plas J, Krýsl D, Varjassyová A, Ghaly Y, Benes V. The MRI volumetry of the posterior fossa and its substructures in trigeminal neuralgia: a validated study. Acta Neurochir (Wien). 2009 Jun;151(6):669-75. doi: 10.1007/s00701-009-0283-8. Epub 2009 Apr 7. PubMed PMID: 19350204.
12) , 15)
Park YS, Ha SM. Does a small posterior fossa increase nerve vascular conflict in trigeminal neuralgia? Acta Radiol. 2014 Dec 8. pii: 0284185114561914. [Epub ahead of print] PubMed PMID: 25487716.
13)
Gnanalingham K, Joshi SM, Lopez B, Ellamushi H, Hamlyn P. Trigeminal neuralgia secondary to Chiari's malformation–treatment with ventriculoperitoneal shunt. Surg Neurol. 2005 Jun;63(6):586-8; discussion 588-9. Review. PubMed PMID:
14)
Rasche D, Kress B, Stippich C, Nennig E, Sartor K, Tronnier VM. Volumetric measurement of the pontomesencephalic cistern in patients with trigeminal neuralgia and healthy controls. Neurosurgery. 2006 Sep;59(3):614-20; discussion 614-20. PubMed PMID: 16955043.
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