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Calcitonin gene-related peptide (CGRP) receptor antagonists in the treatment of migraine


Based on preclinical and clinical studies, the neuropeptide calcitonin gene-related peptide (CGRP) is proposed to play a central role in the underlying pathology of migraine. CGRP and its receptor are widely expressed in both the peripheral and central nervous systems by multiple cell types involved in the regulation of inflammatory and nociceptive responses. Peripheral release of CGRP from trigeminal nerve fibres within the dura and from the cell body of trigeminal ganglion neurons is likely to contribute to peripheral sensitization of trigeminal nociceptors. Similarly, the release of CGRP within the trigeminal nucleus caudalis can facilitate activation of nociceptive second-order neurons and glial cells. Thus, CGRP is involved in the development and maintenance of persistent pain, central sensitization and allodynia, events characteristic of migraine pathology. In contrast, CGRP release within the brain is likely to function in an anti-nociceptive capacity.

Given the role of CGRP in migraine pathology, the potential of CGRP receptor antagonists in the treatment of migraine has been investigated. Towards this end, the non-peptide CGRP receptor antagonists olcegepant and telcagepant have been shown to be effective in the acute treatment of migraine. While telcagepant is being pursued as a frontline abortive migraine drug in a phase III clinical trial, an oral formulation of a novel CGRP receptor antagonist, BI 44370, is currently in phase II clinical trials. Encouragingly, data from clinical studies on these compounds have clearly demonstrated the potential therapeutic benefit of this class of drugs and support the future development of CGRP receptor antagonists to treat migraine and possibly other types of chronic pain.

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Table I


  1. 1.

    Lipton R, Stewart W, Diamond S, et al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001; 41: 646–57

  2. 2.

    Stewart W, Lipton R, Celentano D, et al. Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors. JAMA 1991; 267: 64–9

  3. 3.

    Bigal ME, Lipton RB. The epidemiology, burden, and comorbidities of migraine. Neurol Clin 2009; 27(2): 321–34

  4. 4.

    Moskowitz MA. The visceral organ brain: implications for the pathophysiology of vascular head pain. Neurology 1991; 41 (2 Pt 1): 182–6

  5. 5.

    Goadsby PJ. Recent advances in understanding migraine mechanisms, molecules and therapeutics. Trends Mol Med 2007; 13(1): 39–44

  6. 6.

    McCulloch J, Uddman R, Kingman T, et al. Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci U S A 1986; 83: 5731–5

  7. 7.

    O’Conner T, Van der Kooy D. Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries. J Neurosci 1988; 8: 2468–76

  8. 8.

    Blau JN, Dexter SL. The site of pain origin during migraine attacks. Cephalalgia 1981; 1(3): 143–7

  9. 9.

    Link AS, Kuris A, Edvinsson L. Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system. J Headache Pain 2008; 9(1): 5–12

  10. 10.

    Humphrey P, Feniuk W. Mode of action of the antimigraine drug sumatriptan. Trends Pharmacol Sci 1991; 12(12): 444–6

  11. 11.

    Bolay H, Reuter U, Dunn A, et al. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002; 8(2): 136–42

  12. 12.

    Hargreaves R. New migraine and pain research. Headache 2007; 47 Suppl. 1: S26–43

  13. 13.

    Pietrobon D. Migraine: new molecular mechanisms. Neuroscientist 2005; 11(4): 373–86

  14. 14.

    Buzzi M, Bonamini M, Moskowitz M. Neurogenic model of migraine. Cephalalgia 1995; 15: 277–80

  15. 15.

    O’Conner T, Van der Kooy D. Pattern of intracranial and extracranial projections of trigeminal ganglion cells. J Neurosci 1986; 6: 2200–7

  16. 16.

    Edvinsson L, Goadsby P. Neuropeptides in migraine and cluster headache. Cephalalgia 1994; 14: 320–7

  17. 17.

    Hargreaves R, Shepheard S. Pathophysiology of migraine: new insights. Can J Neurol Sci 1999; 26 Suppl. 3: S12–9

  18. 18.

    Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev Neurosci 2003; 4(5): 386–98

  19. 19.

    Amara S, Arriza J, Leff S, et al. Expression in brain of amessenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide. Science 1985; 229: 1094–7

  20. 20.

    Juaneda C, Dumont Y, Quirion R. The molecular pharmacology of CGRP and related peptide receptor subtypes. Trends Pharmacol Sci 2000; 21(11): 432–8

  21. 21.

    Steenbergh P, Hoppener J, Zandberg J, et al. A second human calcitonin/CGRP gene. FEBS Lett 1985; 183: 403–7

  22. 22.

    Van Rossum D, Hanisch U, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev 1997; 21(5): 649–78

  23. 23.

    Rosenfeld M, Mermod J-J, Amara S, et al. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 1983; 304: 129–35

  24. 24.

    Sternini C. Enteric and visceral afferent CGRP neurons: targets of innervation and differential expression patterns. Ann N Y Acad Sci 1992; 657: 170–86

  25. 25.

    Goadsby P, Edvinsson L, Elkman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990; 28: 183–7

  26. 26.

    Bellamy J, Cady R, Durham P. Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients. Headache 2006; 46: 24–33

  27. 27.

    Cady R, Vause C, Ho T, et al. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache 2009; 49: 1258–66

  28. 28.

    Goadsby P, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993; 33: 48–56

  29. 29.

    Lassen L, Haderslev P, Jacobsen V, et al. CGRP may play a causative role in migraine. Cephalalgia 2002; 22(1): 54–61

  30. 30.

    Olesen J, Diener H, Husstedt I, et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004; 350: 1104–10

  31. 31.

    Ottosson A, Edvinsson L. Release of histamine from dural mast cells by substance P and calcitonin gene-related peptide. Cephalalgia 1997; 17(3): 166–74

  32. 32.

    Messlinger K, Hanesch U, Kurosawa M, et al. Calcitonin gene related peptide released from dural nerve fibers mediates increase of meningeal blood flow in the rat. Can J Physiol Pharmacol 1995; 73(7): 1020–4

  33. 33.

    Strassman A, Raymond S, Burnstein R. Sensitization of meningeal sensory neurons and the origin of headaches. Nature 1996; 384: 560–4

  34. 34.

    Durham P, Russo A. New insights into the molecular actions of serotonergic antimigraine drugs. Pharmacol Ther 2002; 94: 77–92

  35. 35.

    Thalakoti S, Patil V, Damodaram S, et al. Neuron-glia signaling in trigeminal ganglion: implications for migraine pathology. Headache 2007; 47(7): 1008–23

  36. 36.

    Zhang XC, Strassman AM, Burstein R, et al. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther 2007; 322(2): 806–12

  37. 37.

    Schaible HG. On the role of tachykinins and calcitonin gene-related peptide in the spinal mechanisms of nociception and in the induction and maintenance of inflammation-evoked hyperexcitability in spinal cord neurons (with special reference to nociception in joints). Prog Brain Res 1996; 113: 423–41

  38. 38.

    Ruda MA, Ling QD, Hohmann AG, et al. Altered nociceptive neuronal circuits after neonatal peripheral inflammation. Science 2000; 289(5479): 628–31

  39. 39.

    Neugebauer V, Rumenapp P, Schaible HG. Calcitonin gene-related peptide is involved in the spinal processing of mechanosensory input from the rat’s knee joint and in the generation and maintenance of hyperexcitability of dorsal horn-neurons during development of acute inflammation. Neuroscience 1996; 71(4): 1095–109

  40. 40.

    Cridland RA, Henry JL. Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II. Neuropeptides 1988; 11(1): 23–32

  41. 41.

    Sun R, Lawand N, Willis W. The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin. Pain 2003; 104: 201–8

  42. 42.

    Sun R, Tu Y, Lawand N, et al. Calcitonin gene-related peptide receptor activation produces PKA- and PKC-dependent mechanical hyperalgesia and central sensitization. J Neurophysiol 2004; 92: 2859–66

  43. 43.

    Galeazza MT, Garry MG, Yost HJ, et al. Plasticity in the synthesis and storage of substance P and calcitonin gene-related peptide in primary afferent neurons during peripheral inflammation. Neuroscience 1995; 66(2): 443–58

  44. 44.

    Oku R, Satoh M, Fujii N, et al. Calcitonin gene-related peptide promotes mechanical nociception by potentiating release of substance P from the spinal dorsal horn in rats. Brain Res 1987; 403(2): 350–4

  45. 45.

    Biella G, Panara C, Pecile A, et al. Facilitatory role of calcitonin gene-related peptide (CGRP) on excitation induced by substance P (SP) and noxious stimuli in rat spinal dorsal horn neurons: an iontophoretic study in vivo. Brain Res 1991; 559(2): 352–6

  46. 46.

    Bennett AD, Chastain KM, Hulsebosch CE. Alleviation of mechanical and thermal allodynia by CGRP(8–37) in arodent model of chronic central pain. Pain 2000; 86(1–2): 163–75

  47. 47.

    Hay DL, Poyner DR, Quirion R. International Union of Pharmacology: LXIX. Status of the calcitonin gene-related peptide subtype 2 receptor. Pharmacol Rev 2008; 60(2): 143–5

  48. 48.

    Poyner D, Sexton P, Marshall I, et al. International Union of Pharmacology: XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev 2002; 54(2): 233–46

  49. 49.

    Mallee J, Salvatore C, LeBourdelles B, et al. Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists. J Biol Chem 2002; 277(16): 14294–8

  50. 50.

    Banerjee S, Evanson J, Harris E, et al. Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding. BMC Pharmacol 2006; 15: 6–9

  51. 51.

    Maggi C, Rovero P, Giuliani S, et al. Biological activity of N-terminal fragments of calcitonin gene-related peptide. Eur J Pharmacol 1990; 179: 217–9

  52. 52.

    Zaidi M, Brain S, Tippins J, et al. Structure-activity relationship of human calcitonin-gene-related peptide. Biochem J 1990; 269: 775–80

  53. 53.

    Chiba T, Yamaguchi A, Yamatani T, et al. Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37). Am J Physiol 1989; 256 (2 Pt 1): E331–5

  54. 54.

    Mentlein R, Roos T. Proteases involved in the metabolism of angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), and neuropeptide Y by vascular smooth muscle cells. Peptides 1996; 17: 709–20

  55. 55.

    Hughes SR, Brain SD. A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin. Br J Pharmacol 1991 Nov; 104(3): 738–42

  56. 56.

    Edvinsson L, Nilsson E, Jansen-Olesen I. Inhibitory effect of BIBN4096BS, CGRP8-37, a CGRP antibody and an RNA-Spiegelmer on CGRP induced vasodilatation in the perfused and non-perfused rat middle cerebral artery. Br J Pharmacol 2007; 150: 633–40

  57. 57.

    Rist B, Lacroix J, Entzeroth M, et al. CGRP 27–37 analogues with high affinity to the CGRP1 receptor show antagonistic properties in a rat blood flow assay. Regul Pept 1999; 79(2–3): 153–8

  58. 58.

    Morara S, Wang LP, Filippov V, et al. Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices. Eur J Neurosci 2008; 28(11): 2213–20

  59. 59.

    Levy D, Jakubowski M, Burstein R. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT1B/1D receptor agonists. Proc Natl Acad Sci U S A 2004; 101(12): 4274–9

  60. 60.

    Lennerz JK, Ruhle V, Ceppa EP, et al. Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution. J Comp Neurol 2008; 507(3): 1277–99

  61. 61.

    Moreno M, Cohen Z, Stanimirovic D, et al. Functional calcitonin gene-related peptide type 1 and adrenomedullin receptors in human trigeminal ganglia, brain vessels, and cerebromicrovascular or astroglial cells in culture. J Cereb Blood Flow Metab 1999; 19(11): 1270–8

  62. 62.

    Oliver K, Wainwright A, Edvinsson L, et al. Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature. J Cereb Blood Flow Metab 2002; 22(5): 620–9

  63. 63.

    Edvinsson L, Alm R, Shaw D, et al. Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells. Eur J Pharmacol 2002; 434(1–2): 49–53

  64. 64.

    Petersen KA, Nilsson E, Olesen J, et al. Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo. Cephalalgia 2005; 25(6): 424–32

  65. 65.

    Strassman AM, Weissner W, Williams M, et al. Axon diameters and intradural trajectories of the dural innervation in the rat. J Comp Neurol 2004; 473(3): 364–76

  66. 66.

    Doods H, Hallermayer G, Wu D, et al. Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist. Br J Pharmacol 2000; 129(3): 420–3

  67. 67.

    Rudolf K, Eberlein W, Engel W, et al. Development of human calcitonin gene-related peptide (CGRP) receptor antagonists: 1. Potent and selective small molecule CGRP antagonists. 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2 (1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-l-lysyl]-4-(4-pyridinyl)piperazine: the first CGRP antagonist for clinical trials in acute migraine. J Med Chem 2005; 48(19): 5921–31

  68. 68.

    Edvinsson L, Petersen K. CGRP-receptor antagonism in migraine treatment. CNS Neurol Disord Drug Targets 2007; 6: 240–6

  69. 69.

    Recober A, Russo A. Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs 2007; 10: 566–74

  70. 70.

    Kapoor K, Arulmani U, Heiligers J, et al. Effects of BIBN4096BS on cardiac output distribution and on CGRP-induced carotid haemodynamic responses in the pig. Eur J Pharmacol 2003; 475(1–3): 69–77

  71. 71.

    Salmon A, Damaj M, Marubio L, et al. Altered neuroadaptation in opiate dependence and neurogenic inflammatory nociception in alpha CGRP-deficient mice. Nat Neurosci 2001; 4(4): 357–8

  72. 72.

    Verheggen R, Bumann K, Kaumann A. BIBN4096BS is a potent competitive antagonist of the relaxant effects of alpha-CGRP on human temporal artery: comparison with CGRP(8-37). Br J Pharmacol 2002; 136: 120–6

  73. 73.

    Iovino M, Feifel U, Yong CL, et al. Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers. Cephalalgia 2004; 24(8): 645–56

  74. 74.

    Zhang Z, Winborn C, Marquez de Prado B, et al. Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J Neurosci 2007; 27(10): 2693–703

  75. 75.

    Ferrari M, Roon K, Lipton R, et al. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001; 358(9294): 1668–75

  76. 76.

    Petersen K, Lassen L, Birk S, et al. BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced headache and extracerebral artery dilatation. Clin Pharmacol Ther 2005; 77: 202–13

  77. 77.

    Williams TM, Stump CA, Nguyen DN, et al. Non-peptide calcitonin gene-related peptide receptor antagonists from a benzodiazepinone lead. Bioorg Med Chem Lett 2006; 16(10): 2595–8

  78. 78.

    Burgey CS, Paone DV, Shaw AW, et al. Synthesis of the (3R,6S)-3-amino-6-(2,3-difluorophenyl)azepan-2-one of telcagepant (MK-0974), a calcitonin gene-related peptide receptor antagonist for the treatment of migraine headache. Org Lett 2008; 10(15): 3235–8

  79. 79.

    Moore EL, Burgey CS, Paone DV, et al. Examining the binding properties of MK-0974: a CGRP receptor antagonist for the acute treatment of migraine. Eur J Pharmacol 2009; 602(2–3): 250–4

  80. 80.

    Salvatore C, Hershey J, Corcoran H, et al. Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl) piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther 2008; 324: 416–21

  81. 81.

    Salvatore CA, Hershey JC, Corcoran HA, et al. Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2, 3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-y l]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)-piperidine-1-carbox amide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther 2008; 324(2): 416–21

  82. 82.

    Ho TW, Mannix LK, Fan X, et al. Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology 2008; 70(16): 1304–12

  83. 83.

    Paone D, Shaw A, Nguyen D, et al. Potent, orally bioavailable calcitonin gene-related peptide receptor antagonists for the treatment of migraine: discovery of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide (MK-0974). J Med Chem 2007; 50: 5564–7

  84. 84.

    Connor KM, Shapiro RE, Diener HC, et al. Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 2009; 73(12): 970–7

  85. 85.

    Tepper SJ, Cleves C. Telcagepant, a calcitonin gene-related peptide antagonist for the treatment of migraine. Curr Opin Investig Drugs 2009; 10(7): 711–20

  86. 86.

    Burgey CS, Potteiger CM, Deng JZ, et al. Optimization of azepanone calcitonin gene-related peptide (CGRP) receptor antagonists: development of novel spiropiperidines. Bioorg Med Chem Lett 2009; 19(22): 6368–72

  87. 87.

    Capuano A, De Corato A, Lisi L, et al. Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology. Mol Pain 2009; 5: 43–56

  88. 88.

    Williamson D, Hill R, Shepheard S, et al. The antimigraine 5-HT(1B/1D) agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs. Br J Pharmacol 2001; 133: 1029–34

  89. 89.

    Reddington M, Priller J, Treichel J, et al. Astrocytes and microglia as potential targets for calcitonin gene related peptide in the central nervous system. Can J Physiol Pharmacol 1995; 73: 1047–9

  90. 90.

    Han J, Li W, Neugebauer V. Critical role of calcitonin gene-related peptide 1 receptors in the amygdala in synaptic plasticity and pain behaviour. J Neurosci 2005; 25(46): 10717–28

  91. 91.

    Yu LC, Hou JF, Fu FH, et al. Roles of calcitonin gene-related peptide and its receptors in pain-related behavioral responses in the central nervous system. Neurosci Biobehav Rev 2009; 33(8): 1185–91

  92. 92.

    Olesen J, Burstein R, Ashina M, et al. Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol 2009; 8(7): 679–90

  93. 93.

    Levy D, Burstein R, Strassman A. Mast cell involvement in the pathophysiology of migraine headache: a hypothesis. Headache 2006; 46 Suppl. 1: S13–8

  94. 94.

    Li J, Vause C, Durham P. Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells. Brain Res 2008; 1196: 22–32

  95. 95.

    Vause CV, Durham PL. CGRP stimulation of iNOS and NO release from trigeminal ganglion glial cells involves mitogen-activated protein kinase pathways. J Neurochem 2009; 110(3): 811–21

  96. 96.

    Cheng JK, Ji RR. Intracellular signaling in primary sensory neurons and persistent pain. Neurochem Res 2008; 33(10): 1970–8

  97. 97.

    Adwanikar H, Ji G, Li W, et al. Spinal CGRP1 receptors contribute to supraspinally organized pain behavior and pain-related sensitization of amygdala neurons. Pain 2007; 132(1–2): 53–66

  98. 98.

    Bernard JF, Bandler R. Parallel circuits for emotional coping behaviour: new pieces in the puzzle. J Comp Neurol 1998; 401(4): 429–36

  99. 99.

    Suter MR, Wen YR, Decosterd I, et al. Do glial cells control pain? Neuron Glia Biol 2007; 3(3): 255–68

  100. 100.

    Watkins L, Maier S. Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 2002; 82: 981–1011

  101. 101.

    Watkins L, Milligan E, Maier S. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol 2003; 521: 1–21

  102. 102.

    Wei F, Guo W, Zou S, et al. Supraspinal glial-neuronal interactions contribute to descending pain facilitation. J Neurosci 2008; 28(42): 10482–95

  103. 103.

    Ren K, Dubner R. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol 2008; 21(5): 570–9

  104. 104.

    Guo W, Wang H, Watanabe M, et al. Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci 2007; 27(22): 6006–18

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Dr Durham serves on a scientific advisory board, has received grant support and has served as a consultant for Merck & Co., Inc. Dr Vause has no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

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Correspondence to Paul L. Durham PhD.

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Durham, P.L., Vause, C.V. Calcitonin gene-related peptide (CGRP) receptor antagonists in the treatment of migraine. CNS Drugs 24, 539–548 (2010). https://doi.org/10.2165/11534920-000000000-00000

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  • Migraine
  • Sumatriptan
  • Migraine Attack
  • Trigeminal Ganglion
  • Rizatriptan