Cranial neuralgias: from physiopathology to pharmacological treatment


Cranial neuralgias are paroxysmal painful disorders of the head characterised by some shared features such as unilaterality of symptoms, transience and recurrence of attacks, superficial and “shock-like” quality of pain and the presence of triggering factors. Although rare, these disorders must be promptly recognised as they harbour a relatively high risk for underlying compressive or inflammatory disease. Nevertheless, misdiagnosis is frequent. Trigeminal and glossopharyngeal neuralgias are sustained in most cases by a neurovascular conflict in the posterior fossa resulting in a hyperexcitability state of the trigeminal circuitry. If the aetiology of trigeminal neuralgia (TN) and other typical neuralgias must be brought back to the peripheral injury, their pathogenesis could involve central allodynic mechanisms, which, in patients with inter-critical pain, also engage the nociceptive neurons at the thalamic-cortical level. Currently available medical treatments for TN and other cranial neuralgias are reviewed.

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  1. 1.

    Headache Classification Subcommittee of the International Headache Society (2004). The International Classification of Headache Disorders, 2nd edition. Cephalalgia 24[Suppl 1]:9–160

    Google Scholar 

  2. 2.

    Katusic S, Williams DB, Beard CM et al (1991) Epidemiology and clinical features of idiopathic trigeminal neuralgia and glossopharyngeal neuralgia: similarities and differences. Neuroepidemiology 10:276–281

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    MacDonald BK, Cockerel OC, Sander JW (2000) The incidence and lifetime prevalence of neurological disorders in a community based study in UK. Brain 123:665–676

    PubMed  Article  Google Scholar 

  4. 4.

    Hooge JP, Redekop WK (1995) Trigeminal neuralgia in multiple sclerosis. Neurology 45:1294–1296

    PubMed  CAS  Google Scholar 

  5. 5.

    De Simone R, Marano E, Brescia Morra V et al (2005) A clinical comparison of trigeminal neuralgic pain in patients with and without underlying multiple sclerosis. Neurol Sci 26:S150–S151

    PubMed  Article  Google Scholar 

  6. 6.

    Rozen TD (2004) Trigeminal Neuralgia and glossopharyngeal neuralgia. Neurol Clin Am 22:185–206

    Article  Google Scholar 

  7. 7.

    Smyth P, Greenough G, Stommel E (2003) Familial trigeminal neuralgia: case reports and review of the literature. Headache 43:910–915

    PubMed  Article  Google Scholar 

  8. 8.

    Savica R, Laganà A, Siracusano R et al (2007) Idiopathic familial trigeminal neuralgia: a case report. Neurol Sci 28:196–198

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Scrivani SJ, Keith DA, Kulich R et al (1998) Posttraumatic gustatory neuralgia: a clinical model of trigeminal neuropathic pain. J Orofac Pain 12:287–292

    PubMed  CAS  Google Scholar 

  10. 10.

    Goadsby PJ, Matharu MS, Boes CJ (2001) SUNCT syndrome or trigeminal neuralgia with lacrimation. Cephalalgia 21:82–83

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Evans WR, Bassiur JP (2005) Pretrigeminal neuralgia. Headache 45:242–244

    PubMed  Article  Google Scholar 

  12. 12.

    Rushton JG, MacDonald HN (1957) Trigeminal neuralgia. Special considerations of nonsurgical treatment. JAMA 165:437–440

    CAS  Google Scholar 

  13. 13.

    Cheng TM, Cascino TL, Onofrio BM (1993) Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors. Neurology 43:2298–2302

    PubMed  CAS  Google Scholar 

  14. 14.

    Obermann M, Yoon MS, Ese D et al (2007) Impaired trigeminal nociceptive processing in patients with trigeminal neuralgia. Neurology 69:835–841

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Burchiel KJ, Slavin KV (2000) On the natural history of trigeminal neuralgia. Neurosurgery 46:152–155

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Manzoni GC. Torelli P (2005) Epidemiology of typical and atypical craniofacial neuralgias. Neurol Sci 26[Suppl 2]:s65–67

    PubMed  Article  Google Scholar 

  17. 17.

    Coffey RJ, Fromm GH (1991) Familial trigeminal neuralgia and Charcot-Marie-Tooth neuropathy. Report of two families and review. Surg Neurol 35:49–53

    CAS  Google Scholar 

  18. 18.

    Cruccu G, Biasiotta A, Galeotti F et al (2006) Diagnostic accuracy of trigeminal reflex testing in trigeminal neuralgia. Neurology 66:139–141

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Rushton JG, Stevens JC, Miller RH (1981) Glossopharyngeal (vagoglossopharyngeal) neuralgia. A study of 217 cases. Arch Neurol 38:201–205

    PubMed  CAS  Google Scholar 

  20. 20.

    Bruyn GW (1983) Glossopharyngeal neuralgia. Cephalalgia 3:143–157

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Montalbetti L, Ferrandi D, Pergami P, Savoldi F (1995) Elongated styloid process and Eagle’s syndrome. Cephalalgia 15:80–93

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Bruyn GW (1984) Nervus intermedius neuralgia (Hunt). Cephalalgia 4:71–78

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Kuhn WF, Kuhn SC, Gilberstadt H (1997) Occipital neuralgias: clinical recognition of a complicated headache. A case series and literature review. J Orofac Pain 11:158–165

    PubMed  CAS  Google Scholar 

  24. 24.

    Tancredi A, Caputi F (2004) Greater occipital neuralgia and arthrosis of C1-2 lateral joint. Eur J Neurol 11:573–574

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Bruyn GW (1983) Superior laryngeal neuralgia. Cephalalgia 3:235–240

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Jannetta PJ (1967) Arterial compression of the trigeminal nerve at the pons in patients with trigeminal neuralgia. J Neurosurg 26[Suppl]:159–162

    PubMed  Google Scholar 

  27. 27.

    Boecher-Schwarz HG, Bruehl K, Kessel G (1998) Sensitivity and specificity of MRA in the diagnosis of neurovascular compression in patients with trigeminal neuralgia. A correlation of MRA and surgical findings. Neuroradiology 40:88–95

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Barker FG, Jannette PJ, Bissonette DJ et al (1996) The longterm outcome of microvascular decompression for trigeminal neuralgia. N Engl J Med 334:1077–1183

    PubMed  Article  Google Scholar 

  29. 29.

    Leandri M, Eldridge P, Miles J (1998) Recovery of nerve conduction following microvascular decompression for trigeminal neuralgia. Neurology 51:1641–1646

    PubMed  CAS  Google Scholar 

  30. 30.

    Miles JB, Eldridge PR, Haggett CE, Bowsher D (1997) Sensory effects of microvascular decompression in trigeminal neuralgia. J Neurosurg 86:193–196

    PubMed  CAS  Google Scholar 

  31. 31.

    Cruccu G, Leandri M, Feliciani M, Manfredi M (1990) Idiopathic and symptomatic trigeminal pain. J Neurol Neurosurg Psychiatry 53:1034–1042

    PubMed  CAS  Google Scholar 

  32. 32.

    MarinkoviĆ S, TodoroviĆ V, Gibo H et al (2007) The trigeminal vasculature pathology in patients with neuralgia. Headache 47:1334–1339

    PubMed  Article  Google Scholar 

  33. 33.

    Burchiel KJ (1980) Abnormal impulse generation in focally demyelinated trigeminal roots. J Neurosurg 53:674–683

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    Bennetto L, Patel NK, Fuller G (2007) Trigeminal neuralgia and its management. BMJ 334:201–205

    PubMed  Article  Google Scholar 

  35. 35.

    Love S, Terry Gradidge T, Coakham HB (2001) Trigeminal neuralgia due to multiple sclerosis: ultrastructural findings in trigeminal rhizotomy specimens. Neuropathol Appl Neurobiol 27:238–244

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Gass A, Kitchen N, MacManus DG et al (1997) Trigeminal neuralgia in patients with multiple sclerosis: lesion localization with magnetic resonance imaging. Neurology 49:1142–1144

    PubMed  CAS  Google Scholar 

  37. 37.

    Rappaport ZH, Govrin-Lippmann R, Devor M (1997) An electronmicroscopic analysis of biopsy samples of the trigeminal root taken during microvascular decompressive surgery. Stereotact Funct Neurosurg 68:182–186

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Nurmikko TJ, Eldridge PR (2001) Trigeminal neuralgia pathophysiology, diagnosis and current treatment. Br J Anaesth 87:117–132

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Adams CBT (1989) Microvascular compression: an alternative view and hypothesis. J Neurosurg 57:1–12

    Google Scholar 

  40. 40.

    Hamlyn PJ, King TJ (1992) Neurovascular compression in trigeminal neuralgia: a clinical and anatomical study. J Neurosurg 76:948–952

    PubMed  CAS  Google Scholar 

  41. 41.

    Sindou M, Leston J, Howeidy T et al (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 (Wien) 148:1235–1245

    Article  CAS  Google Scholar 

  42. 42.

    Fromm GH (1991) Pathophysiology of trigeminal neuralgia. In: Fromm GH, Sessle BJ (eds) Trigeminal Neuralgia: current concepts regarding pathogenesis and treatment. Butterworth-Heinemann, Boston, pp 105–130

    Google Scholar 

  43. 43.

    Szapiro J, Sindou M (1985) Prognostic factors in microvascular decompression for trigeminal neuralgia. Neurosurgery 17:920–929

    PubMed  Article  Google Scholar 

  44. 44.

    Amir R, Devor M (2000) Functional cross-excitation between afferent A-and C-neurons in dorsal root ganglia. Neuroscience 95:189–195

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Amir R, Devor M (1996) Chemically mediated cross-excitation in rat dorsal root ganglia. J Neurosci 16:4733–4741

    PubMed  CAS  Google Scholar 

  46. 46.

    Amir R, Michaelis M, Devor M (1999) Membrane potential oscillations in dorsal root ganglion neurons: role in normal electrogenesis and neuropathic pain. J Neurosci 19:8589–8596

    PubMed  CAS  Google Scholar 

  47. 47.

    Kerr FWL (1967) Pathology of trigeminal neuralgia: light and electron microscopic observations. J Neurosurg 26:151–156

    PubMed  Google Scholar 

  48. 48.

    Beaver DL (1967) Electron microscopy of the Gasserian ganglion in trigeminal neuralgia. J Neurosurg 26:138–150

    PubMed  Google Scholar 

  49. 49.

    Kanai A, Saito M, Hoka S (2006) Subcutaneous sumatriptan for refractory trigeminal neuralgia. Headache 46:577–582.

    PubMed  Article  Google Scholar 

  50. 50.

    Argoff CE (2002) A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain 18[Suppl 6]:S177–S181

    PubMed  Article  Google Scholar 

  51. 51.

    Aoki KR (2005) Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology 26:785–793

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Wiffen PJ, McQuay HJ, Moore RA (2005) Carbamazepine for acute and chronic pain. Cochrane Database Syst Rev (3):CD005451

  53. 53.

    Rappaport ZH, Devor M (1994) Trigeminal neuralgia: the role of self-sustaining discharge in the trigeminal ganglion. Pain 56:127–138

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Backonja MM (2002) Use of anticonvulsants for treatment of neuropathic pain. Neurology 59:S14–S17

    PubMed  Google Scholar 

  55. 55.

    Taylor JC, Brauer S, Espir LE (1981) Long-term treatment of trigeminal neuralgia with carbamazepine. Postgrad Med J 5:16–18

    Google Scholar 

  56. 56.

    Pellock JM (1987) Carbamazepine side effects in children and adults. Epilepsia 28:S64–S70

    PubMed  Article  Google Scholar 

  57. 57.

    Zakrzewska JM, Lopez BC (2005) Trigeminal neuralgia. Clin Evid: 1669–1677

  58. 58.

    Canavero S, Bonicalzi V (2006) Drug therapy of trigeminal neuralgia. Expert Rev Neurother 6:429–440

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Raskin NH (1988) Facial pain. In: Headache. New York: Churchill Livingstone:333–374.

    Google Scholar 

  60. 60.

    Wiffen PJ, McQuay HJ, Edwards JE, Moore RA (2005) Gabapentin for acute and chronic pain. Cochrane Database Syst Rev (3:CD005452

  61. 61.

    Obermann M, Yoon MS, Sensen K et al (2007) Efficacy of pregabalin in the treatment of trigeminal neuralgia. Cephalalgia 28:174–181

    PubMed  Google Scholar 

  62. 62.

    Zakrzewska JM, Chaudhry Z, Nurmikko TJ et al (1997) Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind, placebo-controlled, crossover trial. Pain 73:223–230

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Lunardi G, Leandri M, Albano C et al (1997) Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 48:1714–1717

    PubMed  CAS  Google Scholar 

  64. 64.

    Gilron I, Booher SL, Rowan JS, Max MB (2001) Topiramate in trigeminal neuralgia: a randomized, placebo-controlled multiple crossover pilot study. Clin Neuropharmacol 24:109–112

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Zvartaui-Hind M, Din MU, Gilani A et al (2000) Topiramate relieves refractory trigeminal neuralgia in MS patients. Neurology 55:1587–1588

    Google Scholar 

  66. 66.

    Fromm GH, Terrence CF, Chattha AS (1984) Baclofen in the treatment of trigeminal neuralgia: double blind study and long term follow-up. Ann Neurol 15:240–244

    PubMed  Article  CAS  Google Scholar 

  67. 67.

    Kayser V, Aubel B, Hamon M, Bourgoin S (2002) The antimigraine 5-HT1B/1D receptor agonists, sumatriptan, zolmitriptan and dihydroergotamine, attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. Br J Pharmacol 137:1287–1297

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Tsui JK, Eisen A, Stoessl AJ et al (1986) Double-blind study of botulinum toxin in spasmodic torticollis. Lancet 2:245–247

    PubMed  Article  CAS  Google Scholar 

  69. 69.

    Difazio M, Jabbari B (2002) A focused review of the use of botulinum toxins for low back pain. Clin J Pain 18[Suppl 6]:S155–S162

    PubMed  Article  Google Scholar 

  70. 70.

    Silberstein SD, Stark SR, Lucas SM et al; BoNTA-039 Study Group (2005) Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 80:1126–1137

    PubMed  CAS  Google Scholar 

  71. 71.

    Piovesan EJ, Teive HG, Kowacs PA et al (2005) An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 65:1306–1308

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Roberto De Simone.

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De Simone, R., Ranieri, A., Bilo, L. et al. Cranial neuralgias: from physiopathology to pharmacological treatment. Neurol Sci 29, 69 (2008).

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  • Cranial neuralgias
  • Trigeminal neuralgia
  • Glossopharyngeal neuralgia
  • Physiopathology
  • Treatment
  • Review