Trigeminal autonomic cephalalgias: current insights into pathophysiology, diagnosis, and therapeutic strategies

Authors

DOI:

https://doi.org/10.48208/HeadacheMed.2026.1

Keywords:

Trigeminal-autonomic cephalalgias, Cluster headache, Paroxysmal hemicrania, Hemicrania continua, SUNCT, SUNA

Abstract

Background
Trigeminal autonomic cephalalgias (TAC) are primary headache disorders characterized by unilateral craniofacial pain, usually periorbital or temporal, accompanied by ipsilateral autonomic symptoms such as tearing, nasal congestion, conjunctival injection, miosis, and ptosis. They include cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks (SUNCT and SUNA). Diagnosis depends on attack duration, frequency, and intensity, though clinical overlap may occur. Accurate identification is crucial, as treatment differs among subtypes. Understanding TAC pathophysiology, particularly trigeminal autonomic activation, is essential for improving diagnosis, distinguishing them from similar disorders like migraine, and optimizing therapeutic management.
Results
Trigeminal autonomic cephalalgias represent a group of rare but disabling primary headache disorders characterized by overlapping pathophysiological pathways involving the hypothalamus and trigemino-autonomic reflex. Advances in neuroimaging and neuromodulation have refined understanding of their mechanisms and expanded therapeutic options beyond traditional pharmacotherapy. Early recognition and tailored, mechanism-based interventions remain essential to improving outcomes.
Conclusions
We believe it is very important and necessary to offer a comprehensive and up-to-date review of trigeminal autonomic headaches, emphasizing their common and distinctive clinical features, the underlying neurobiological mechanisms, and current evidence-based approaches for timely diagnosis and treatment.

 

Downloads

Download data is not yet available.

References

1. Root S, Knievel K. Classification and diagnosis of trigeminal autonomic cephalalgias. In: Levin M, editor. Comprehensive Review of Headache Medicine [Internet]. 2nd ed., New York: Oxford Academic; 2025.

2. Oksuz N, Özge A. Gray Zones in the Trigeminal Autonomic Cephalalgias. Neurological Sciences and Neurophysiology 2023;40:15–9. Doi:10.4103/nsn.nsn_108_22.

3. Moskatel LS, Ogunlaja O, Zhang N. Prevalence, demographics, comorbidities, and treatment patterns of patients with the trigeminal autonomic cephalalgias: a retrospective analysis of United States electronic health records. BMC Neurol 2025;25:299. Doi:10.1186/s12883-025-04314-1.

4. May A, Schwedt TJ, Magis D, Pozo-Rosich P, Evers S, Wang S-J. Cluster headache. Nat Rev Dis Primers 2018;4:18006. Doi:10.1038/nrdp.2018.6.

5. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211. Doi:10.1177/0333102417738202.

6. Petersen AS, Lund N, Goadsby PJ, Belin AC, Wang S-J, Fronczek R, et al. Recent advances in diagnosing, managing, and understanding the pathophysiology of cluster headache. Lancet Neurol 2024;23:712–24. Doi:10.1016/S1474-4422(24)00143-1.

7. Goadsby PJ, Cohen AS, Matharu MS. Trigeminal autonomic cephalalgias: Diagnosis and treatment. Curr Neurol Neurosci Rep 2007;7:117–25. Doi:10.1007/s11910-007-0006-6.

8. Coppola G, Arruda MA, Ashina M, Barloese M, Belin AC, Bottiroli S, et al. Hallmarks of primary headache: part 3 – cluster headache. J Headache Pain 2025;26:196. Doi:10.1186/s10194-025-02145-6.

9. Lansbergen CS, Fronczek R, Wilbrink LA, Cohen SP, de Vos CC, Huygen FJPM. 15. Cluster Headache. Pain Practice 2025;25. Doi:10.1111/papr.70050.

10. Wei DY, Goadsby PJ. Cluster headache pathophysiology — insights from current and emerging treatments. Nat Rev Neurol 2021;17:308–24. Doi:10.1038/s41582-021-00477-w.

11. Vila-Pueyo M, Hoffmann J, Romero-Reyes M, Akerman S. Brain structure and function related to headache: Brainstem structure and function in headache. Cephalalgia 2019;39:1635–60. Doi:10.1177/0333102418784698.

12. Burish M. Cluster Headache and Other Trigeminal Autonomic Cephalalgias. Continuum (N Y) 2018;24:1137–56. Doi:10.1212/CON.0000000000000625.

13. Lund NLT, Petersen AS, Fronczek R, Tfelt-Hansen J, Belin AC, Meisingset T, et al. Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments—a consensus article. J Headache Pain 2023;24:121. Doi:10.1186/s10194-023-01660-8.

14. Diener HC, May A. Drug Treatment of Cluster Headache. Drugs 2022;82:33–42. Doi:10.1007/s40265-021-01658-z.

15. Brandt RB, Doesborg PGG, Haan J, Ferrari MD, Fronczek R. Pharmacotherapy for Cluster Headache. CNS Drugs 2020;34:171–84. Doi:10.1007/s40263-019-00696-2.

16. Mckenzie D, Hinson M. Occipital Nerve Block. Treasure Island (FL): StatPearls Publishing; n.d.

17. Lazzari ZT, Palmisani S, Hill B, Al‐Kaisy A, Lambru G. A prospective case series of sphenopalatine ganglion pulsed radiofrequency therapy for refractory chronic cluster headache. Eur J Neurol 2020;27:1190–6. Doi:10.1111/ene.14176.

18. Guo Y, Wang X, Bian J, Dou Z, Yang L, Ni J, et al. Low-temperature plasma radiofrequency ablation for the management of refractory cluster headache. Videosurgery and Other Miniinvasive Techniques 2020:362–8. Doi:10.5114/wiitm.2020.100739.

19. Simmonds L, Lagrata S, Stubberud A, Cheema S, Tronvik E, Matharu M, et al. An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache. Front Neurol 2023;14. Doi:10.3389/fneur.2023.1100426.

20. Goadsby PJ, Sahai-Srivastava S, Kezirian EJ, Calhoun AH, Matthews DC, McAllister PJ, et al. Safety and efficacy of sphenopalatine ganglion stimulation for chronic cluster headache: a double-blind, randomised controlled trial. Lancet Neurol 2019;18:1081–90. Doi:10.1016/S1474-4422(19)30322-9.

21. Brandt RB, Wilbrink LA, de Coo IF, Haan J, Mulleners WM, Huygen FJPM, et al. A prospective open label 2–8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache. EBioMedicine 2023;98:104895. Doi:10.1016/j.ebiom.2023.104895.

22. Andreani JCM, Bruera O, Lisicki M, Bashkansky D, Piedimonte F. Long-term effectiveness of combined unilateral sphenopalatine and occipital nerve stimulation in patients with refractory chronic cluster headache. Cephalalgia Rep 2025;8. Doi:10.1177/25158163251355554.

23. Henningsen MJ, Larsen JG, Karlsson WK, Christensen RH, Al‐Khazali HM, Amin FM, et al. Epidemiology and clinical features of paroxysmal hemicrania: A systematic review and meta‐analysis. Headache: The Journal of Head and Face Pain 2024;64:5–15. Doi:10.1111/head.14658.

24. Goadsby PJ. Indomethacin-Responsive Headache Disorders. Continuum (N Y) 2024;30:488–97. Doi:10.1212/CON.0000000000001409.

25. Cittadini E, Matharu MS, Goadsby PJ. Paroxysmal hemicrania: a prospective clinical study of 31 cases. Brain 2008;131:1142–55. Doi:10.1093/brain/awn010.

26. Paliwal VK, Uniyal R. Paroxysmal Hemicrania. Neurol India 2021;69:S135–43. Doi:10.4103/0028-3886.315982.

27. Baraldi C, Pellesi L, Guerzoni S, Cainazzo MM, Pini LA. Therapeutical approaches to paroxysmal hemicrania, hemicrania continua and short lasting unilateral neuralgiform headache attacks: a critical appraisal. J Headache Pain 2017;18:71. Doi:10.1186/s10194-017-0777-3.

28. Cheung S, Oliveira R, Goadsby PJ. Melatonin in hemicrania continua and paroxysmal hemicrania. Cephalalgia 2024;44. Doi:10.1177/03331024231226196.

29. Al-Khazali HM, Al-Khazali S, Iljazi A, Christensen RH, Ashina S, Lipton RB, et al. Prevalence and clinical features of hemicrania continua in clinic-based studies: A systematic review and meta-analysis. Cephalalgia 2023;43. Doi:10.1177/03331024221131343.

30. Bahra A. Paroxysmal hemicrania and hemicrania continua: Review on pathophysiology, clinical features and treatment. Cephalalgia 2023;43. Doi:10.1177/03331024231214239.

31. Pareja J, Caminero A, Franco E, Casado J, Pascual J, del Río MS. Dose, Efficacy and Tolerability of Long-Term Indomethacin Treatment of Chronic Paroxysmal Hemicrania and Hemicrania Continua. Cephalalgia 2001;21:906–10. Doi:10.1046/j.1468-2982.2001.00287.x.

32. Osiowski A, Stolarz K, Taterra D. How can you manage an indomethacin-responsive headache in someone who cannot take indomethacin? Curr Opin Neurol 2025;38:254–61. Doi:10.1097/WCO.0000000000001347.

33. Al Khalili Y, Veerapaneni K. Short-lasting unilateral neuralgiform headache. Treasure Island (FL): StatPearls Publishing; 2023.

34. Kang M-K, Cho S-J. SUNCT, SUNA and short-lasting unilateral neuralgiform headache attacks: Debates and an update. Cephalalgia 2024;44. Doi:10.1177/03331024241232256.

35. Diener HC, Tassorelli C, Dodick DW. Management of Trigeminal Autonomic Cephalalgias Including Chronic Cluster. JAMA Neurol 2023;80:308. Doi:10.1001/jamaneurol.2022.4804.

36. Lambru G, Stubberud A, Rantell K, Lagrata S, Tronvik E, Matharu MS. Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis. J Neurol Neurosurg Psychiatry 2021;92:233–41. Doi:10.1136/jnnp-2020-323999.

37. Benoliel R, Sharav Y, Haviv Y, Almoznino G. Tic, Triggering, and Tearing: From CTN to SUNHA. Headache: The Journal of Head and Face Pain 2017;57:997–1009. Doi:10.1111/head.13040.

Downloads

Published

2026-03-03

Issue

Section

Review

How to Cite

1.
Trigeminal autonomic cephalalgias: current insights into pathophysiology, diagnosis, and therapeutic strategies. Headache Med [Internet]. 2026 Mar. 3 [cited 2026 Mar. 3];17(1):7-19. Available from: https://headachemedicine.com.br/hm/article/view/1382