Title: Physiological basis and Mechanism of Headache: Recent advances

Authors: Abhishek Sinha, Renu Bhatia

 DOI: https://dx.doi.org/10.18535/jmscr/v9i5.28

Abstract

Headache is a very common complaint for which a patient reports to the physician. It can cause discomfort in some patients whereas it can be a harbinger of some serious medical conditions in others. In our earlier review on headache published in the same journal, we had discussed some of the well established physiological basis and mechanisms behind different types of headaches. The aim of this review is to unravel some of the recent advances in the knowledge of the mechanisms of the various types of headache and also discuss about two lesser discussed types of headaches experienced by general population.

Keywords: Headache, Migraine, Tension type Headache, Cluster headache, Pathophysiological mechanisms, Primary Exercise Headache, Menstrual Related Headache, Recent advances.

References

  1. Abhishek Sinha, Renu Bhatia. Physiological basis and Mechanism of Headache: Mini Review. Journal of Medical Science and Clinical Research. 2019; 7(3): 408-413.
  2. Headache disorders. World Health Organization /Fact sheets. Web link: https://www.who.int/news-room/fact-sheets/detail/headache-disorders.
  3. Epidemiology of Headache. Global Year Against Headache Oct 2011-Oct 2012. International Association for the Study of Pain.
  4. Ray BK, Paul N, Hazra A, Das S, Ghosal MK, Misra AK, Banerjee TK, Chaudhuri A, Das SK. Prevalence, burden, and risk factors of migraine: A community-based study from Eastern India. Neurol India 2017;65:1280-1288.
  5. Kulkarni GB, Rao GN, Gururaj G, Stovner LJ, Steiner T. Headache disorders and public ill-health in India:Prevalence estimates in Karnataka state. J Headache Pain 2015:16:67-77.
  6. Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH et al (2016) Metaanalysis of 375,000 individuals identifies 38 susceptibility loci for migraine.Nat Genet 48(8):856–866.
  7. Andreou AP, Edvinsson L. Mechanisms of migraine as a chronic evolutive condition. J Headache Pain. 2019 Dec 23;20(1):117.
  8. Schneggenburger R, Neher E (2005) Presynaptic calcium and control of vesicle fusion. CurrOpinNeurobiol 15(3):266–274.
  9. De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L et al(2003) Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet;33(2):192–196.
  10. Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S et al (2005) Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 366(9483):371–377.
  11. Van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T et al (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 41(5):701–710.
  12. Wessman M, Terwindt GM, Kaunisto MA, Palotie A, Ophoff RA (2007).Migraine: a complex genetic disorder. Lancet Neurol 6(6):521–532.
  13. Gerring ZF, McRae AF, Montgomery GW, Nyholt DR (2018) Genome-wide DNA methylation profiling in whole blood reveals epigenetic signatures associated with migraine. BMC Genomics 19(1):69.
  14. Kurth T, Mohamed S, Maillard P, Zhu YC, Chabriat H, Mazoyer B et al (2011) Headache, migraine, and structural brain lesions and function: population based epidemiology of vascular ageing-MRI study. BMJ. 342:c7357.
  15. Arkink EB, Palm-Meinders IH, Koppen H, Milles J, van Lew B, Launer LJ et al (2019) Microstructural white matter changes preceding white matter hyperintensities in migraine. Neurology 93(7):e688–e694.
  16. Palm-Meinders IH, Koppen H, Terwindt GM, Launer LJ, Konishi J, Moonen JM et al (2012) Structural brain changes in migraine. JAMA. 308(18):1889–1897.
  17. Magon S, May A, Stankewitz A, Goadsby PJ, Tso AR, Ashina M et al (2015) Morphological abnormalities of thalamic subnuclei in migraine: a multicenter MRI study at 3 tesla. J Neurosci 35(40):13800–13806.
  18. Granziera C, Daducci A, Romascano D, Roche A, Helms G, Krueger G et al (2014) Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3 T. Hum Brain Mapp 35(4):1461–1468.
  19. Chen Z, Chen X, Liu M, Ma L, Yu S (2019) Volume of hypothalamus as a diagnostic biomarker of chronic migraine. Front Neurol 10:606.
  20. May A, Bahra A, Buchel C, et al. Hypothalamic activation in cluster headache attacks. Lancet 1998; 352:275–278.
  21. Matharu MS, Cohen AS, Frackowiak RS, et al. Posterior hypothalamic activation in paroxysmal hemicrania. Ann Neurol 2006; 59: 535–545.
  22. Sprenger T, Valet M, Platzer S, et al. SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression. Pain 2005; 113: 422–426.
  23. Dahlstrom A and Fuxe K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I demonstration of monoamines in the cell bodies of Brain stem neurons (Suppl 232). Acta PhysiolScand 1964; 62: 1–55.
  24. Charbit AR, Akerman S and Goadsby PJ. Trigeminocervical complex responses after lesioning dopaminergic A11 nucleus are modified by dopamine and serotonin mechanisms. Pain 2011; 152: 2365–2376.
  25. Goadsby PJ and Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain 1994; 117(Pt 3): 427–434.
  26. Tuka B, SzaboÅL N, ToÅLth E, et al. Release of PACAP-38 in episodic cluster headache patients – an exploratory study. J Headache Pain 2016; 17: 69.
  27. Burstein R, Noseda R and Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci 2015; 35: 6619–6629.
  28. Hoffmann J, Baca SM, Akerman S. Neurovascular mechanisms of migraine and cluster headache. J Cereb Blood Flow Metab. 2019;39(4):573-594.
  29. Vedova Chris Della, Stuart Cathcart, Alan Dohnalek, Vanessa Lee, Mark R
  30. Hutchinson, Maarten A Immink, et al. Peripheral interleukin-1β levels are elevated in chronic tension-type headache patients. Pain Res Manag. 2013 Nov-Dec; 18(6): 301–306.
  31. Hasan Sjahrir,andMoh Hasan Machfoed. Tumour Necrosis Factor-Α, Interleukin-1 and Interleukin-6 Serum Levels and Its Correlation with Pain Severity in Chronic Tension-Type Headache Patients: Analysing Effect of Dexketoprofen Administration. J Med Sci. 2017 Feb 15; 5(1): 54–57.
  32. Susanti, R. (2020). Immunology Aspects in Tension-Type Headache Chronicity. Biomedical Journal of Indonesia; 6(2): 1-10.
  33. Ribeiro Felipe A. Pinho, Waldiceu A. Verri Jr and Isaac M. Chiu. Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation. Trends Immunol. 2017 January; 38(1): 5–19.
  34. Ren Ke and Ronald Dubner. Interactions between the immune and nervous systems in pain. Nat Med. 2010 November; 16(11): 1267–1276.
  35. Meeus Mira, Jo Nijs, Linda Hermans, Dorien Goubert & Patrick Calders. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain orchronic fatigue syndromes and fibromyalgia patients: Peripheral and central mechanisme. Expert Opin. Ther. Targets (2013); 17(9).
  36. Voscopoulos C. and M. Lema. When does acute pain become chronic? British Journal of Anaesthesia 105 (S1): i69–i85 (2010).
  37. Puca F, Genco S, Prudenzano MP, et al. for the Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches. Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. Cephalalgia 1999;19:159–164.
  38. Woo AK. Depression and Anxiety in Pain. Rev Pain 2010; 4 : 8-12.
  39. Mattoo B, Tanwar S, Bhatia R, Tripathi M, Bhatia R. Repetitive Transcranial magnetic stimulation in chronic tension type headache: A pilot study. Indian J Med Res 2019;150:73-80.
  40. Kumar, A., Mattoo, B., Bhatia, R.,Kumaran , S , Bhatia, R.et al. Neuronavigation based 10 sessions of repetitive transcranial magnetic stimulation therapy in chronic migraine: an exploratory study. Neurol Sci.2021 Jan;42(1):131-139.
  41. Upadhyaya P, Nandyala A, Ailani J. Primary Exercise Headache. CurrNeurolNeurosci Rep. 2020;20(5):9. Published 2020 Apr 15.
  42. Doepp F, Valdueza J, Schreiber S. Incompetence of internal jugular valve in patients with primary exertional headache: a risk factor? Cephalalgia. 2007;28:182–5.
  43. Heckmann J, Hilz M, Katalinic A, Marthol H, Mück-Weymann M, Neundörfer B. Myogenic cerebrovascular autoregulation in migraine measured by stress transcranial Doppler sonography. Cephalalgia. 1998;18:133–7.
  44. Moy G, Gupta V. Menstrual Related Headache. [Updated 2021 Feb 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557451/
  45. Frederiksen SD, Bekker-Nielsen Dunbar M, Snoer AH, Deen M, Edvinsson L. Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case-Control and Case-Crossover Settings: A Systematic Review and Meta-Analysis. Headache. 2020 Jun;60(6):1132-1164.
  46. Brunklaus A, Schorge S, Smith AD, Ghanty I, Stewart K, Gardiner S, Du J, Pérez-Palma E, Symonds JD, Collier AC, Lal D, Zuberi SM. SCN1A variants from bench to bedside-improved clinical prediction from functional characterization. Hum Mutat. 2020 Feb;41(2):363-374.

Corresponding Author

Abhishek Sinha

Associate Professor, Department of Physiology, All India Institute of Medical Sciences, Guwahati, India