Volume : 3, Issue : 3, JUL 2019


Damit Dhiman, Shubham Bhardwaj


A migraine is not “just a headache”. It is a neurological condition, which can be very distressing and disabling. Generally it is a one-sided throbbing or pulsating headache that is at least moderately intense and can be aggravated by physical activity. It is quite often associated with nausea and vomiting, as well as increased sensitivity to light, sound and even due to different types of smell. Research is continuing, but at present, we do not know what causes a migraine, there is no clear diagnostic test and, as yet, there is no cure. However, there are many ways to help manage the condition and lessen its impact - ultimately reducing the disruption caused to everyday life. It affects more than 10% of the general population. Regardless of recent progress in drug therapy for preventing and treating migraine remains unsatisfactory for many patients. One problem that slows the development of new therapeutic approaches is the limited understanding of migraine neurobiology. This article reviews current understanding of the mechanisms underlying migraine and approaches to treating it.


Article : Download PDF

Cite This Article

Article No : 2

Number of Downloads : 4


  1. Abdallah K, Artola A, Monconduit L, Dallel R, Luccarini P. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats. PLoS One 8:e73022, 2013.
  2. Abe J, Hosokawa H, Okazawa M, Kandachi M, Sawada Y, Yamanaka K, Matsumura K, Kobayashi S. TRPM8 protein localization in trigeminal ganglion and taste papillae. Brain Res 136: 91–98, 2005.
  3. Abizaid A. Ghrelin and dopamine: new insights on the peripheral regulation of appetite. J Neuroendocrinol 21: 787–793, 2009.
  4. Abizaid A, Horvath TL. Ghrelin and the central regulation of feeding and energy balance. Indian J Endocrinol Metab 16: S617– 626, 2012.
  5. Adam JA, Menheere PP, van Dielen FM, Soeters PB, Buurman WA, Greve JW. Decreased plasma orexin-A levels in obese individuals. Int J Obes Relat Metab Disord 26: 274 –276, 2002.
  6. Adamantidis A, Salvert D, Goutagny R, Lakaye B, Gervasoni D, Grisar T, Luppi PH, Fort P. Sleep architecture of the melanin-concentrating hormone receptor 1-knockout mice. Eur J Neurosci 27: 1793–1800, 2008.
  7. Adrian TE, Allen JM, Bloom SR, Ghatei MA, Rossor MN, Roberts GW, Crow TJ, Tatemoto K, Polak JM. Neuropeptide Y distribution in human brain. Nature 306: 584 –586, 1983.
  8. Dodick DW. Chronic Daily Headache. New England Journal of Medicine 2006; 354: 158-165.
  9. Hans-Christoph D, David WD, Peter JG, Richard BL, Jes O, et al. Chronic migraine-classification, characteristics and Nature Reviews Neurology 2012.
  10. Mayo Clinic DD, M.D. Complex migraine. 2011.
  11. Bigal ME, Serrano D, Reed M, Lipton RB. Chronic migraine in the population: Burden, diagnosis, and satisfaction with treatment. Neurology 2008; 71: 559-566.
  12. Topamax Highlights of Prescription Information 2009.
  13. Eroglu C, Allen NJ, Susman MW. Gabapentin Receptor alpha 2 delta-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis.
  14. Headache Classification C, Olesen J, Bousser MG. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006; 26: 742-746.
  15. Mathew NT, Frishberg BM, Gawel M. Botulinum Toxin Type A (BOTOX®) for the Prophylactic Treatment of Chronic Daily Headache: A Randomized, Double-Blind, Placebo-Controlled Trial. Headache: The Journal of Head and Face Pain 2005; 45: 293-307.
  16. Campbell DA, Tonks EM, Hay KM. An Investigation of the Salt and Water Balance in Migraine. British Medical Journal 195; 1424-1429.
  17. Hadjikhani N, Sanchez del Rio M, Wu O. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proceedings of the National Academy of Sciences 2001; 98: 4687-4692.
  18. James MF, Smith JM, Boniface SJ, Huang CL-H, Leslie RA, et al. Cortical spreading depression and migraine: new insights from imaging? TRENDS In Neuroscience 2001; 226-271.
  19. Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38: 701–713, 2003.
  20. Yamanaka A, Kunii K, Nambu T, Tsujino N, Sakai A, Matsuzaki I, Miwa Y, Goto K, Sakurai T. Orexin-induced food intake involves neuropeptide Y pathway. Brain Res 859: 404 – 409, 2000.
  21. Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M, Block GD, Sakaki Y, Menaker M, Tei H. Resetting central and peripheral circadian oscillators in transgenic rats. Science 288: 682– 685, 2000.
  22. Yasui Y, Saper CB, Cechetto DF. Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat. J Comp Neurol 308: 293–310, 1991.
  23. Yeo GS, Heisler LK. Unraveling the brain regulation of appetite: lessons from genetics. Nat Neurosci 15: 1343–1349, 2012.
  24. Yettefti K, Orsini JC, Perrin J. Characteristics of glycemia-sensitive neurons in the nucleus tractus solitarii: possible involvement in nutritional regulation. Physiol Behav 61: 93–100, 1997.
  25. Yi CX, Serlie MJ, Ackermans MT, Foppen E, Buijs RM, Sauerwein HP, Fliers E, Kalsbeek A. A major role for perifornical orexin neurons in the control of glucose metabolism in rats. Diabetes 58: 1998 –2005, 2009.
  26. Young RF, Brechner T. Electrical stimulation of the brain for relief of intractable pain due to cancer. Cancer 57: 1266 –1272, 1986.
  27. Yuan PQ, Yang H. Neuronal activation of brain vagal-regulatory pathways and upper gut enteric plexuses by insulin hypoglycemia. Am J Physiol Endocrinol Metab 283: E436 –E448, 2002.
  28. Zagami AS, Edvinsson L, Goadsby PJ. Pituitary adenylate cyclase activating polypeptide and Migraine. Ann Clin Transl Neurol 1: 1036 –1040, 2014.
  29. Zagami AS, Edvinsson L, Hoskin KL, Goadsby PJ. Stimulation of the superior sagittal sinus causes extracranial release of PACAP. Cephalalgia 15: 109, 1995.
  30. Zagami AS, Lambert GA. Craniovascular application of capsaicin activates nociceptive thalamic neurons in the cat. Neurosci Lett 121: 187–190, 1991.
  31. Zagami AS, Lambert GA. Stimulation of cranial vessels excites nociceptive neurones in several thalamic nuclei of the cat. Exp Brain Res 81: 552–566, 1990.
  32. Zanchin G, Dainese F, Trucco M, Mainardi F, Mampreso E, Maggioni F. Osmophobia in migraine and tension-type headache and its clinical features in patients with migraine. Cephalalgia 27: 1061–1068, 2007.
  33. Zhang X, Levy D, Kainz V, Noseda R, Jakubowski M, Burstein R. Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol 69: 855– 865, 2011.
  34. Zhang X, Levy D, Noseda R, Kainz V, Jakubowski M, Burstein R. Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. J Neurosci 30: 8807– 8814, 2010.
  35. Zhang XC, Strassman AM, Burstein R, Levy D. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther 322: 806 – 812, 2007.
  36. Ziegler DK, Hassanein RS, Kodanaz A, Meek JC. Circadian rhythms of plasma cortisol in migraine. J Neurol Neurosurg Psychiatry 42: 741–748, 1979.
  37. Zurak N. Role of the suprachiasmatic nucleus in the pathogenesis of migraine attacks. Cephalalgia 17: 723–728, 1997.
  38. Tottene A, Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, Pietrobon D. Familial hemiplegic migraine mutations increase Ca2_x0005_ inflflux through single human CaV2.1 channels and decrease maximal CaV21 current density in neurons. Proc Natl Acad Sci USA 99: 13284 –13289, 2002.
  39. Tracey I. Imaging pain. Br J Anaesth 101: 32–39, 2008.
  40. Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA 289: 65– 69, 2003.
  41. Tso AR, Trujillo A, Guo C, C, Goadsby PJ, Seeley WW. The anterior insula shows heightened interictal intrinsic connectivity in migraine without aura. Neurolgy 84:1043–1050, 2015.
  42. Tsuneki H, Wada T, Sasaoka T. Role of orexin in the central regulation of glucose and energy homeostasis. Endocr J 59: 365–374, 2012.
  43. Tuka B, Helyes Z, Markovics A, Bagoly T, Szolcsanyi J, Szabo N, Toth E, Kincses ZT, Vecsei L, Tajti J. Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Cephalalgia 33: 1085–1095, 2013.
  44. Uddman R, Edvinsson L. Neuropeptides in the cerebral circulation. Cerebrovasc Brain Metab Rev 1: 230 –252, 1989.
  45. Uddman R, Edvinsson L, Ekman R, Kingman T, McCulloch J. Innervation of the feline cerebral vasculature by nerve fifibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P. Neurosci Lett 62: 131–136, 1985.
  46. Uddman R, Goadsby PJ, Jansen I, Edvinsson L. PACAP, a VIP-like peptide, immuno-histochemical localization and effect upon cat pial arteries and cerebral blood flflow. J Cereb Blood Flow Metab 13: 291–297, 1993.
  47. Uddman R, Moller S, Nilsson T, Nystrom S, Ekstrand J, Edvinsson L. Neuropeptide Y Y1 and neuropeptide Y Y2 receptors in human cardiovascular tissues. Peptides 23:927–934, 2002.
  48. Uddman R, Tajti J, Hou M, Sundler F, Edvinsson L. Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2. Cephalalgia 22: 112–116, 2002.
  49. Ullmer C, Schmuck K, Kalkman HO, Lubbert H. Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett 370: 215–221, 1995.
  50. Gozke E, Unal M, Engin H, Gurbuzer N. An Observational Study on the Association between Migraines and Tension Type Headaches in Patients Diagnosed with Metabolic Syndrome. ISRN Neurology. 2013; 2013: 4.
  51. Sachdev A, Marmura MJ. Metabolic Syndrome and Migraine. Frontiers in Neurology. 2012; 3: 161.
  52. Salmasi M, Amini L, Javanmard SH, Saadatnia M. Metabolic syndrome in migraine headache: A case-control study. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2014; 19: 13-17.
  53. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, et al. Harrison's Manual of Medicine 18th Edition. New York: McGraw Hill Medical 2013.
  54. Liu H, Huaiting G, Xiang J. Resting state brain activity in patients with migraine: a magnetoencephalography study. The Journal of headache and Pain 2015:16-42.
  55. Xue T, Yuan K, Zhao L. Intrinsic Brain Network Abnormalities in Migraines without Aura Revealed in Resting-State fMRI. PLOS ONE. 2012: e52927.
  56. Schwedt TJ. Multisensory Integration in Migraine. Curr Opin Neurol. 2013: 248-253.
  57. Strassman A, Raymond S, Burstein R. Sensitization of meningeal sensory neurons and the origin of headaches. Nature. 1996; 384: 560 - 564.
  58. Tso AR, Trujillo A, Guo CC, Goadsby PJ, Seeley WW, et al. The anterior insula shows heightened interictal intrinsic connectivity in migraine without aura. Neurology. 2015: 1043-1050.
  59. National Nutrient Database for Standard Reference Release 26. Washington.
  60. Pages N, Orosco M, Rouch C, Yao O, Jacquot C, Bohuon C. Refeeding after 72 hour fasting alters neuropeptide Y and monoamines in various cerebral areas in the rat. Comp Biochem Physiol Comp Physiol 106: 845– 849, 1993.
  61. Palm-Meinders IH, Koppen H, Terwindt GM, Launer LJ, Konishi J, Moonen JME, Bakkers JTN, Hofman PAM, van Lew B, Middelkoop HAM, van Buchem MA, Ferrari MD, Kruit MC. Structural brain changes in migraine. JAMA 308: 1889 –1897, 2012.
  62. Palmer JE, Guillard FL, Laurijssens BE, Wentz AL, Dixon RM, Williams PM. A randomised, single-blind, placebo-controlled, adaptive clinical trial of GW274150, a selective iNOS inhibitor, in the treatment of acute migraine. Cephalalgia 29: 124, 2009.
  63. Panda S, Hogenesch JB. It’s all in the timing: many clocks, many outputs. J Biol Rhythms 19: 374 –387, 2004.
  64. Paranjape SA, Vavaiya KK, Kale AY, Briski KP. Habituation of insulin-induced hypoglycemic transcription activation of lateral hypothalamic orexin-A-containing neurons to recurring exposure. Regul Pept 135: 1– 6, 2006.
  65. Pardutz A, Krizbai I, Multon S, Vecsei L, Schoenen J. Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis. Neuroreport 11: 3071–3075, 2000.