Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2021, Vol. 35 ›› Issue (4): 115-122.doi: 10.6040/j.issn.1673-3770.0.2020.354

Previous Articles     Next Articles

The pathomechanism and treatment progress of trigeminal neuralgia

XU Feifei1,WU Hao2   

  1. 1. Nantong University Medical School, Nantong 226001, Jiangsu, China;
    2. Department of Otolaryngology & Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
  • Published:2021-08-05

Abstract: Trigeminal neuralgia(TN)is the most common craniofacial pain, but its pathogenesis has not been fully understood. TN often manifests as a sudden, severe, brief, stabbing, and recurrent pain in one or more branches of the trigeminal nerve. Classification methods, various pathogenesis(such as central hypothesis, nerve compression theory, inflammatory response theory, bioresonance hypothesis, and ion channel alteration theory)and clinical multidisciplinary treatment progress were reviewed to provide references for personalized treatment of TN.

Key words: Trigeminal neuralgia, Classification, Mechanism, Ion channel, Treatment

CLC Number: 

  • R76
[1] Jones MR, Urits I, Ehrhardt KP, et al. A comprehensive review of trigeminal neuralgia[J]. Curr Pain Headache Rep, 2019, 23(10): 74. doi:10.1007/s11916-019-0810-0.
[2] 张恺. 三叉神经痛诊断标准探讨及病因、治疗研究进展[J]. 国际神经病学神经外科学杂志, 2018, 45(4): 434-437. doi:10.16636/j.cnki.jinn.2018.04.025.
[3] Cruccu G, Finnerup NB, Jensen TS, et al. Trigeminal neuralgia: New classification and diagnostic grading for practice and research[J]. Neurology, 2016, 87(2): 220-228. doi:10.1212/WNL.0000000000002840.
[4] 中华医学会神经外科学分会功能神经外科学组,中国医师协会神经外科医师分会功能神经外科专家委员会,上海交通大学颅神经疾病诊治中心.三叉神经痛诊疗中国专家共识[J].中华外科杂志,2015,53(9):657-664. doi:10.3760/cma.j.issn.0529-5815.2015.09.005.
[5] 刘清军. 《三叉神经痛诊疗中国专家共识》解读[J]. 中国现代神经疾病杂志, 2018, 18(9): 643-646. doi:10.3969/j.issn.1672-6731.2018.09.003. LIU Qingjun. Interpretation of “Chinese expert consensus on diagnosis and treatment of trigeminal neuralgia”[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2018, 18(9): 643-646. doi:10.3969/j.issn.1672-6731.2018.09.003.
[6] Kerr FW, Miller RH. The pathology of trigeminal neuralgia. Electron microscopic studies[J]. Arch Neurol, 1966, 15(3): 308-319. doi:10.1001/archneur.1966.00470150086014.
[7] Cheshire WP Jr. Trigeminal neuralgia: Diagnosis and treatment[J]. Curr Neurol Neurosci Rep, 2005, 5(2): 79-85. doi:10.1007/s11910-005-0003-6.
[8] 丁丽华, 于生元. 实验性三叉神经痛研究进展[J]. 中国疼痛医学杂志, 2004, 10(4): 231-233. doi:10.3969/j.issn.1006-9852.2004.04.016.
[9] 王红润. 不同抗癫痫药物对三叉神经痛的干预效果分析[J]. 慢性病学杂志, 2016, 17(7): 814-815, 818. doi:10.16440/j.cnki.1674-8166.2016.07.033.
[10] 赵光明, 陈克敏, 柴维敏, 等. 三叉神经痛患者与健康志愿者丘脑1H-MRS的比较[J]. 放射学实践, 2008, 23(3): 250-253. doi:10.3969/j.issn.1000-0313.2008.03.006. ZHAO Guangming, CHEN Kemin, CHAI Weimin, et al. Comparison of 1H MR spectroscopic findings of thalamus in trigeminal neuralgia patients and healthy volunteers[J]. Radiologic Practice, 2008, 23(3): 250-253. doi:10.3969/j.issn.1000-0313.2008.03.006.
[11] Dandy WE. Concerning the cause of trigeminal neuralgia[J]. Am J Surg, 1934, 24(2): 447-455. doi:10.1016/S0002-9610(34)90403-7.
[12] Sarsam Z, Garcia-Fiñana M, Nurmikko TJ, et al. The long-term outcome of microvascular decompression for trigeminal neuralgia[J]. Br J Neurosurg, 2010, 24(1): 18-25. doi:10.3109/02688690903370289.
[13] Devor M, Amir R, Rappaport ZH. Pathophysiology of trigeminal neuralgia: the ignition hypothesis[J]. Clin J Pain, 2002, 18(1): 4-13. doi:10.1097/00002508-200201000-00002.
[14] 张毅, 贺学农, 苏海, 等.伽玛刀治疗原发性三叉神经痛 45 例疗效分析[J]. 第三军医大学学报, 2012, 34(14): 1476-1477
[15] Kerr FW. Pathology of trigeminal neuralgia: light and electron microscopic observations[J]. J Neurosurg, 1967, 26(1): 151-156. doi:10.3171/jns.1967.26.1part2.0151.
[16] 赵可, 徐兆水, 唐林卡, 等. 老年三叉神经痛298例病因研究[J]. 中国中西医结合耳鼻咽喉科杂志, 2007, 15(5): 360-362. doi:10.3969/j.issn.1007-4856.2007.05.014.
[17] Love S, Coakham HB. Trigeminal neuralgia: pathology and pathogenesis[J]. Brain, 2001, 124(Pt 12): 2347-2360. doi:10.1093/brain/124.12.2347.
[18] Donahue JH, Ornan DA, Mukherjee S. Imaging of vascular compression syndromes[J]. Radiol Clin North Am, 2017, 55(1): 123-138. doi:10.1016/j.rcl.2016.08.001.
[19] Chen GQ, Wang XS, Wang L, et al. Arterial compression of nerve is the primary cause of trigeminal neuralgia[J]. Neurol Sci, 2014, 35(1): 61-66. doi:10.1007/s10072-013-1518-2.
[20] Sindou M, Leston J, Decullier E, et al. Microvascular decompression for primary trigeminal neuralgia: long-term effectiveness and prognostic factors in a series of 362 consecutive patients with clear-cut neurovascular conflicts who underwent pure decompression[J]. J Neurosurg, 2007, 107(6): 1144-1153. doi:10.3171/jns-07/12/1144.
[21] 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[J]. Acta Neurochir, 2018, 160(5): 971-976. doi:10.1007/s00701-018-3468-1.
[22] Sicard A. Bernard pierson 1925: 1978[J]. Arch Anat Cytol Pathol, 1978, 26(2): 79-80.
[23] Liang L, Diao YL, Xu QY, et al. Transcranial segment of the trigeminal nerve: macro-/microscopic anatomical study using sheet plastination[J]. Acta Neurochir(Wien), 2014, 156(3): 605-612. doi:10.1007/s00701-013-1920-9.
[24] Uçeyler N, Rogausch JP, Toyka KV, et al. Differential expression of cytokines in painful and painless neuropathies[J]. Neurology, 2007, 69(1): 42-49. doi:10.1212/01.wnl.0000265062.92340.a5.
[25] Lis K, Grygorowicz T, Cudna A, et al. Inhibition of TNF reduces mechanical orofacial hyperalgesia induced by Complete Freund's Adjuvant by a TRPV1-dependent mechanism in mice[J]. Pharmacol Rep, 2017, 69(6): 1380-1385. doi:10.1016/j.pharep.2017.05.013.
[26] Wang X, Liang H, Zhou C, et al. Sensitization induces hypersensitivity in trigeminal nerve[J]. Clin Exp Allergy, 2012, 42(11): 1638-1642. doi:10.1111/j.1365-2222.2012.04051.x.
[27] Pei Z, Sang H, Li R, et al. Infrasound-induced hemodynamics, ultrastructure, and molecular changes in the rat myocardium[J]. Environ Toxicol, 2007, 22(2): 169-175. doi:10.1002/tox.20244.
[28] Jia DZ, Li G. Bioresonance hypothesis: a new mechanism on the pathogenesis of trigeminal neuralgia[J]. Med Hypotheses, 2010, 74(3): 505-507. doi:10.1016/j.mehy.2009.09.056.
[29] Sahu MK, Satapathy T, Netam AK, et al. Structural architecture and signal transduction of Ion channels: a review[J]. Rese Jour Pharmacol and Pharmacod, 2018, 10(1): 38. doi:10.5958/2321-5836.2018.00007.1.
[30] Subramanyam P, Colecraft HM. Ion channel engineering: perspectives and strategies[J]. J Mol Biol, 2015, 427(1): 190-204. doi:10.1016/j.jmb.2014.09.001.
[31] 张宗明, 裘法祖. 离子通道与疾病[J]. 世界华人消化杂志, 2005, 13(5): 585-587. doi:10.3969/j.issn.1009-3079.2005.05.001. ZHANG Zongming, QIU Fazu. Ion channels and diseases[J]. World Chinese Journal of Digestology, 2005, 13(5): 585-587. doi:10.3969/j.issn.1009-3079.2005.05.001.
[32] Gambeta E, Chichorro JG, Zamponi GW. Trigeminal neuralgia: an overview from pathophysiology to pharmacological treatments[J]. Mol Pain, 2020, 16: 1744806920901890. doi:10.1177/1744806920901890.
[33] Levinson SR, Luo SJ, Henry MA. The role of sodium channels in chronic pain[J]. Muscle Nerve, 2012, 46(2): 155-165. doi:10.1002/mus.23314.
[34] Linley JE, Rose K, Ooi L, et al. Understanding inflammatory pain: Ion channels contributing to acute and chronic nociception[J]. Pflugers Arch, 2010, 459(5): 657-669. doi:10.1007/s00424-010-0784-6.
[35] Ahn HS, Dib-Hajj SD, Cox JJ, et al. A new Nav1.7 sodium channel mutation I234T in a child with severe pain[J]. Eur J Pain, 2010, 14(9): 944-950. doi:10.1016/j.ejpain.2010.03.007.
[36] Matthews EA, Wood JN, Dickenson AH. Na(v)1.8-null mice show stimulus-dependent deficits in spinal neuronal activity[J]. Mol Pain, 2006, 2: 5. doi:10.1186/1744-8069-2-5.
[37] Dib-Hajj SD, Black JA, Waxman SG. NaV1.9: a sodium channel linked to human pain[J]. Nat Rev Neurosci, 2015, 16(9): 511-519. doi:10.1038/nrn3977.
[38] Lolignier S, Bonnet C, Gaudioso C, et al. The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia[J]. Cell Rep, 2015, 11(7): 1067-1078. doi:10.1016/j.celrep.2015.04.027.
[39] Moulin DE. Pain in central and peripheral demyelinating disorders[J]. Neurol Clin, 1998, 16(4): 889-898. doi:10.1016/s0733-8619(05)70103-1.
[40] Henry MA, Luo SJ, Foley BD, et al. Sodium channel expression and localization at demyelinated sites in painful human dental pulp[J]. J Pain, 2009, 10(7): 750-758. doi:10.1016/j.jpain.2009.01.264.
[41] Littleton JT, Ganetzky B. Ion channels and synaptic organization: analysis of the Drosophila genome[J]. Neuron, 2000, 26(1):35-43. doi:10.1016/s0896-6273(00)81135-6.
[42] Yost CS. Potassium channels:basic aspects, functional roles, and medical significance[J].Anesthesiology,1999,90(4):1186-1203. doi: 10.1097/00000542-199904000-00035.
[43] Yoshida S, Matsumoto S. Effects of alpha-dendrotoxin on K+ currents and action potentials in tetrodotoxin-resistant adult rat trigeminal ganglion neurons[J]. J Pharmacol Exp Ther, 2005, 314(1): 437-445. doi:10.1124/jpet.105.084988.
[44] Beyak MJ, Vanner S. Inflammation-induced hyperexcitability of nociceptive gastrointestinal DRG neurones: the role of voltage-gated Ion channels[J]. Neurogastroenterol Motil, 2005, 17(2): 175-186. doi:10.1111/j.1365-2982.2004.00596.x.
[45] Takeda M, Tanimoto T, Ikeda M, et al. Enhanced excitability of rat trigeminal root ganglion neurons via decrease in A-type potassium currents following temporomandibular joint inflammation[J]. Neuroscience, 2006, 138(2): 621-630. doi:10.1016/j.neuroscience.2005.11.024.
[46] Tsantoulas C, McMahon SB. Opening paths to novel analgesics: the role of potassium channels in chronic pain[J]. Trends Neurosci, 2014, 37(3): 146-158. doi:10.1016/j.tins.2013.12.002.
[47] Barghaan J, Tozakidou M, Ehmke H, et al. Role of N-terminal domain and accessory subunits in controlling deactivation-inactivation coupling of Kv4.2 channels[J]. Biophys J, 2008, 94(4): 1276-1294. doi:10.1529/biophysj.107.111344.
[48] Kraychete DC, Gozzani JL, Kraychete AC. Neuropathic pain: neurochemical aspects[J]. Rev Bras Anestesiol, 2008, 58(5): 498-505, 492-8. doi:10.1590/s0034-70942008000500008.
[49] Takeda M, Tanimoto T, Ikeda M, et al. Activaton of GABAB receptor inhibits the excitability of rat small diameter trigeminal root ganglion neurons[J]. Neuroscience, 2004, 123(2): 491-505. doi:10.1016/j.neuroscience.2003.09.022.
[50] 孔二亮, 吴飞翔, 俞卫锋. 5-羟色胺受体及其在疼痛调控中的研究进展[J]. 第二军医大学学报, 2016, 37(12): 1517-1523. doi:10.16781/j.0258-879x.2016.12.1517. KONG Erliang, WU Feixiang, YU Weifeng. 5-hydroxytryptamine receptor and its role in pain regulation: research progress[J]. Academic Journal of Second Military Medical University, 2016, 37(12): 1517-1523. doi:10.16781/j.0258-879x.2016.12.1517.
[51] Araya EI, Claudino RF, Piovesan EJ, et al. Trigeminal neuralgia: basic and clinical aspects[J]. Curr Neuropharmacol, 2020, 18(2): 109-119. doi:10.2174/1570159X17666191010094350.
[52] Zhang AK, Zhang WB, Xu HS, et al. Diabetes mellitus contributes to carbamazepine resistance in patient with trigeminal neuralgia[J]. Neurosurg Rev, 2021,44(2):1119-1125. doi:10.1007/s10143-020-01304-4.
[53] Kaya O, Hurel C, Gumussuyu G, et al. Bilateral calcaneal insufficiency fractures due to chronic carbamazepine use for trigeminal neuralgia: a case report[J]. Niger J Clin Pract, 2020, 23(4): 574-576. doi:10.4103/njcp.njcp_515_18.
[54] Song HG, Nahm FS. Oxcarbazepine for trigeminal neuralgia may induce lower extremity weakness: a case report[J]. World J Clin Cases, 2020, 8(5): 922-927. doi:10.12998/wjcc.v8.i5.922.
[55] Zhang Y, Su Q, Lian Y, et al. Botulinum toxin type A reduces the expression of transient receptor potential melastatin 3 and transient receptor potential vanilloid type 4 in the trigeminal subnucleus caudalis of a rat model of trigeminal neuralgia[J]. Neuroreport, 2019, 30(10): 735-740. doi:10.1097/wnr.0000000000001268.
[56] De la Torre Canales G, Poluha RL, Lora VM, et al. Botulinum toxin type A applications for masticatory myofascial pain and trigeminal neuralgia: what is the evidence regarding adverse effects?[J]. Clin Oral Investig, 2019, 23(9): 3411-3421. doi:10.1007/s00784-019-03026-4.
[57] Jannetta PJ. Arterial compression of the trigeminal nerve at the Pons in patients with trigeminal neuralgia[J]. J Neurosurg, 1967, 26(1): Suppl:159-Suppl:162. doi:10.3171/jns.1967.26.1part2.0159.
[58] Shi J, Qian YT, Han W, et al. Risk factors for outcomes after microvascular decompression for trigeminal neuralgia[J]. World Neurosurg, 2020, 136: e559-e566. doi:10.1016/j.wneu.2020.01.082.
[59] Sindou M, Leston J, Howeidy T, et al. 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[J]. Acta Neurochir(Wien), 2006, 148(12): 1235-1245. doi:10.1007/s00701-006-0809-2.
[60] Tavakol S, Jackanich A, Strickland BA, et al. Effectiveness of gamma knife radiosurgery in the treatment of refractory trigeminal neuralgia: a case series[J]. Oper Neurosurg(Hagerstown), 2020, 18(6): 571-576. doi:10.1093/ons/opz311.
[61] Petit JH, Herman JM, Nagda S, et al. Radiosurgical treatment of trigeminal neuralgia: evaluating quality of life and treatment outcomes[J]. Int J Radiat Oncol Biol Phys, 2003, 56(4): 1147-1153. doi:10.1016/s0360-3016(03)00264-5.
[62] Régis J, Metellus P, Hayashi M, et al. Prospective controlled trial of gamma knife surgery for essential trigeminal neuralgia[J]. J Neurosurg, 2006, 104(6): 913-924. doi:10.3171/jns.2006.104.6.913.
[63] Liu HB, Ma Y, Zou JJ, et al. Percutaneous microballoon compression for trigeminal neuralgia[J]. Chin Med J(Engl), 2007, 120(3): 228-230.
[64] Udupi BP, Chouhan RS, Dash HH, et al. Comparative evaluation of percutaneous retrogasserian glycerol rhizolysis and radiofrequency thermocoagulation techniques in the management of trigeminal neuralgia[J]. Neurosurgery, 2012, 70(2): 407-412. doi:10.1227/neu.0b013e318233a85f.
[65] Meglio M, Cioni B, Moles A, et al. Microvascular decompression versus percutaneous procedures for typical trigeminal neuralgia: personal experience[J]. Stereotact Funct Neurosurg, 1990, 54/55: 76-79. doi:10.1159/000100194.
[66] 陶圣余,徐雯,高照,等. 针灸治疗三叉神经痛的用穴规律分析[J]. 中国针灸, 2016, 36(2): 207-211. doi:10.13703/j.0255-2930.2016.02.030. TAO Shengyu, XU Wen, GAO Zhao, et al. Analysis on acupoint selection rule of acupuncture for trigeminal neuralgia [J]. Chinese Acupuncture & Moxibustion,2016, 36(2): 207-211. doi:10.13703/j.0255-2930.2016.02.030.
[67] Hu HT, Chen LF, Ma RJ, et al. Acupuncture for primary trigeminal neuralgia: a systematic review and PRISMA-compliant meta-analysis[J]. Complement Ther Clin Pract, 2019, 34: 254-267. doi:10.1016/j.ctcp.2018.12.013.
[1] XIN Min, WANG Shaoming. Neuroimmune mechanisms and therapeutic strategies of inflammatory and infectious olfactory dysfunction [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 111-124.
[2] ZHU Mingqiong, LI Zheng, LIU Ru, TIAN Tao, PENG Jingli, LYU Qianyi, TAN Huaxia. The application of AI screening system based on OCT/OCTA in the evaluation of the effect of anti VEGF treatment in patients with diabetes macular edema [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 68-73.
[3] LU Zhaoyang, ZHAI Zhaoxue, WANG Huikang, SHAO Liting, ZHANG Yu. COVID-19 treatment-induced diabetic ketoacidosis combined with rhino-orbital cerebral mucormycosis: a case report and literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 90-94.
[4] LIU Yijie, LU Xiuzhen, WU Qiuxin. Research rogress of exosomes in the pathogenesis, diagnosis and treatment in ophthalmic diseases [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 135-141.
[5] LI Zan, LU Qi, SHEN Weidong, HOU Zhaohui, WU Nan. Clinical diagnosis and treatment features of 18 cases of necrotizing otitis externa [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 17-22.
[6] LIU Yuzhu, CHEN Yao, YUAN Tiejun, LI Chunsen, LI Bo. Larynx fibrosarcoma: a case report and literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 133-137.
[7] WANG Xiaojie, ZHANG Mingjun, SONG Zheying, CUI Limei, SONG Xicheng. Anti-cancer mechanism and research progress of kaempferol [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 168-178.
[8] GU Zhanxin, ZHAO Zhouyang, ZHANG Xiaobin, YANG Yimei, HUANG Lijin, HUANG Yan. Syndrome differentiation treatment and understanding of traditional Chinese medicine in carotid blowout syndrome [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(4): 100-107.
[9] SHI Jinlian, LI Jianxing, HUANG Yousheng, LIN Mingxuan, LIU Lingyun, LU Yongtian. Research status and progress in diagnosis and treatment of laryngeal inflammatory myofibroblastic tumor [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(4): 186-192.
[10] ZENG Qiying, ZHU Huaming, GUAN Jian, WU Hongmin, YE Haibo, YI Hongliang. Bipolar coagulation forceps applied in the treatment of 6 cases of shamblin type III carotid body tumors [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(3): 70-76.
[11] LI Zhifu, GAO Yu. Mechanistic study and prevention of visual field defects after vitrectomy [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(3): 168-176.
[12] LI Zhicheng, YAN Ya, DAI Liangping, YING Junjie, WANG Renzhong. Research progress of animal models of olfactory disorders [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(2): 158-167.
[13] WU Wei, WANG Lei, CHEN Sheng, LI Lianyong, WANG Gang. Multidisciplinary research and advances in gastro-oesophageal reflux disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 1-14.
[14] LIU Lianlian, LI Jinrang. Obstructive sleep apnea and laryngopharyngeal reflux [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 15-22.
[15] MA Li, GAO Zhan, LI Pengqi, NI Qianwei. Current status of anatomical research on nasal orbital ethmoid and concurrent zygomatic bone fracture complications [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(5): 126-130.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!