Insights into the pharmacological targeting of the trigeminocervical complex in the context of treatments of migraine

Expert Review of Neurotherapeutics

Volumn 13, Issue 9, 2013, Pages 1041-1059

  Akerman, Simon ^a   Romero Reyes, Marcela ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NEW YORK UNIVERSITY COLLEGE OF DENTISTRY   (United States)

Author keywords

Brainstem; CGRP receptor antagonists; Migraine; NSAIDs; Preventives; Trigeminocervical complex; Triptans

Indexed keywords

ACETYLSALICYLIC ACID; CALCITONIN GENE RELATED PEPTIDE RECEPTOR ANTAGONIST; DIHYDROERGOTAMINE; ELETRIPTAN; ERGOTAMINE; IBUPROFEN; INDOMETACIN; KETOROLAC; LY 2951742; NAPROXEN; NARATRIPTAN; NITRIC OXIDE SYNTHASE INHIBITOR; NONSTEROID ANTIINFLAMMATORY AGENT; OLCEGEPANT; OREXIN A; OREXIN B; PARACETAMOL; RIZATRIPTAN; SEROTONIN 1B AGONIST; SEROTONIN 1B RECEPTOR; SEROTONIN 1D AGONIST; SEROTONIN 1D RECEPTOR; SEROTONIN 1F AGONIST; SEROTONIN 1F RECEPTOR; SEROTONIN AGONIST; SUMATRIPTAN; TELCAGEPANT; TOPIRAMATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZOLMITRIPTAN; ANALGESIC AGENT;

BRAIN REGION; BRAIN STEM; CLINICAL TRIAL (TOPIC); DIENCEPHALON; DRUG MECHANISM; DRUG TARGETING; DURA MATER; HEADACHE; HUMAN; MIGRAINE; NOCICEPTION; NONHUMAN; REVIEW; TRIGEMINAL NUCLEUS; TRIGEMINOCERVICAL COMPLEX; ANIMAL; BRAIN CIRCULATION; DRUG EFFECTS; MIGRAINE DISORDERS; PATHOPHYSIOLOGY; TRIGEMINAL NERVE; VASCULARIZATION;

ANALGESICS; ANIMALS; CEREBROVASCULAR CIRCULATION; DURA MATER; HUMANS; MIGRAINE DISORDERS; TRIGEMINAL NERVE; TRIGEMINAL NUCLEI;

EID: 84895191259     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/14737175.2013.827472     Document Type: Review

References (209)

1. Lipton RB, Bigal ME, Diamond M, Freitag F., Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 68(5), 343-349 (2007).
2. Lipton RB, Stewart WF, Diamond S, Diamond M.L., Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 41, 646-657 (2001).
3. Stewart WF, Ricci JA, Chee E, Morganstein D., Lipton R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA 290(18), 2443-2454 (2003).
4. Andlin-Sobocki P., Jonsson B, Wittchen H.U., Olesen J. Cost of disorders of the brain in Europe. Eur. J. Neurol. 12(Suppl 1), 1-27 (2005).
5. Goadsby PJ, Lipton RB, Ferrari MD Migraine-current understanding and treatment. N. Engl. J. Med. 346(4), 257-270 (2002).
6. Bernstein C, Burstein R. Sensitization of the trigeminovascular pathway: perspective and implications to migraine pathophysiology. J. Clin. Neurol. 8(2), 89-99 (2012).
7. Akerman S, Holland PR, Goadsby PJ Diencephalic and brainstem mechanisms in migraine. Nat. Rev. Neurosci. 12(10), 570-584 (2011).
8. Goadsby PJ, Charbit AR, Andreou A.P., Akerman S., Holland PR. Neurobiology of migraine. Neuroscience 161(2), 327-341 (2009).
9. Goadsby PJ, Zagami AS Stimulation of the superior sagittal sinus increases metabolic activity and blood flow in certain regions of the brainstem and upper cervical spinal cord of the cat. Brain 114(Pt 2), 1001-1011 (1991).
10. Kaube H, Keay KA, Hoskin K.L., Bandler R., Goadsby PJ. Expression of c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following stimulation of the superior sagittal sinus in the cat. Brain Res. 629(1), 95-102 (1993).
11. Burstein R, Yamamura H, Malick A., Strassman AM. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J. Neurophysiol. 79(2), 964-982 (1998).
12. Bartsch T, Goadsby PJ The trigeminocervical complex and migraine: current concepts and synthesis. Curr. Pain Headache Rep. 7(5), 371-376 (2003).
13. Johnston MM, Jordan SE, Charles AC Pain referral patterns of the C1-C3 nerves: Implications for headache disorders. Ann. Neurol. (2013).
14. Bartsch T, Goadsby PJ Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain 125(Pt 7), 1496-1509 (2002).
15. Goadsby PJ, Knight YE, Hoskin KL Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat. Pain 73(1), 23-28 (1997).
16. Bartsch T, Goadsby PJ Anatomy and physiology of pain referral in primary and cervicogenic headache disorders. Headache Curr. 2, 42-48 (2005).
17. Malick A, Burstein R. Cells of origin of the trigeminohypothalamic tract in the rat. J. Comp. Neurol. 400(1), 125-144 (1998).
18. Malick A, Strassman RM, Burstein R. Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J. Neurophysiol. 84(4), 2078-2112 (2000).
19. Malick A, Jakubowski M, Elmquist J.K., Saper CB, Burstein R. A neurohistochemical blueprint for pain-induced loss of appetite. Proc. Natl Acad. Sci. USA 98(17), 9930-9935 (2001).
20. Benjamin L, Levy MJ, Lasalandra MP et al. Hypothalamic activation after stimulation of the superior sagittal sinus in the cat: a Fos study. Neurobiol. Dis. 16(3), 500-505 (2004).
21. Liu Y, Broman J, Zhang M., Edvinsson L. Brainstem and thalamic projections from a craniovascular sensory nervous centre in the rostral cervical spinal dorsal horn of rats. Cephalalgia 29(9), 935-948 (2009).
22. Matsushita M, Ikeda M, Okado N. The cells of origin of the trigeminothalamic, trigeminospinal and trigeminocerebellar projections in the cat. Neuroscience 7(6), 1439-1454 (1982).
23. Shigenaga Y, Nakatani Z, Nishimori T., Suemune S, Kuroda R, Matano S. The cells of origin of cat trigeminothalamic projections: especially in the caudal medulla. Brain Res. 277(2), 201-222 (1983).
24. Knight YE, Classey JD, Lasalandra MP et al. Patterns of fos expression in the rostral medulla and caudal pons evoked by noxious craniovascular stimulation and periaqueductal gray stimulation in the cat. Brain Res. 1045 (1-2), 1-11 (2005).
25. Hoskin KL, Bulmer DCE, Lasalandra M, Jonkman A., Goadsby PJ. Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation. J. Anat. 198, 29-35 (2001).
26. Lambert GA, Hoskin KL, Zagami AS Cortico-NRM influences on trigeminal neuronal sensation. Cephalalgia 28(6), 640-652 (2008).
27. Edelmayer RM, Vanderah TW, Majuta L et al. Medullary pain facilitating neurons mediate allodynia in headache-related pain. Ann. Neurol. 65(2), 184-193 (2009).
28. Kaube H, Hoskin KL, Goadsby PJ Activation of the trigeminovascular system by mechanical distension of the superior sagittal sinus in the cat [see comments]. Cephalalgia 12(3), 133-136 (1992).
29. Strassman AM, Raymond SA, Burstein R. Sensitization of meningeal sensory neurons and the origin of headaches. Nature 384(6609), 560-564 (1996).
30. Romero-Reyes M., Akerman S, Nguyen E et al. Spontaneous Behavioral Responses in the Orofacial Region: A Model of Trigeminal Pain in Mouse. Headache 53(1), 137-151 (2013).
31. Akerman S, Holland PR, Lasalandra M.P., Goadsby PJ. Oxygen inhibits neuronal activation in the trigeminocervical complex after stimulation of trigeminal autonomic reflex, but not during direct dural activation of trigeminal afferents. Headache 49(8), 1131-1143 (2009).
32. Akerman S, Holland PR, Summ O, Lasalandra M.P., Goadsby PJ. A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization. Brain 135(Pt 12), 3664-3675 (2012).
33. Bartsch T, Knight YE, Goadsby PJ Activation of 5-HT(1B/1D) receptor in the periaqueductal gray inhibits nociception. Ann. Neurol. 56(3), 371-381 (2004).
34. Knight YE, Goadsby PJ The periaqueductal grey matter modulates trigeminovascular input: a role in migraine? Neuroscience 106(4), 793-800 (2001).
35. Knight YE, Bartsch T, Kaube H., Goadsby PJ. P/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine? J. Neurosci. 22(5), RC213 (2002).
36. Bartsch T, Levy MJ, Knight Y.E., Goadsby PJ. Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus. Pain 117 (1-2), 30-39 (2005).
37. Bartsch T, Levy MJ, Knight Y.E., Goadsby PJ. Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain 109(3), 367-378 (2004).
38. Magis D, Schoenen J. Advances and challenges in neurostimulation for headaches. Lancet Neurol. 11(8), 708-719 (2012).
39. Goadsby PJ. The pharmacology of headache. Prog. Neurobiol. 62(5), 509-525 (2000).
40. Aurora SK, Rozen TD, Kori S.H., Shrewsbury SB. A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache 49(6), 826-837 (2009).
41. Ferrari MD. Treatment of migraine attacks with sumatriptan. The Subcutaneous Sumatriptan International Study Group. N. Engl. J. Med. 325(5), 316-321 (1991).
42. Humphrey PP, Feniuk W. Mode of action of the anti-migraine drug sumatriptan. Trends Pharmacol. Sci. 12(12), 444-446 (1991).
43. Moskowitz MA. The neurobiology of vascular head pain. Ann. Neurol. 16(2), 157-168 (1984).
44. Moskowitz MA. Basic mechanisms in vascular headache. Neurol. Clin. 8(4), 801-815 (1990).
45. Longmore J, Shaw D, Smith D et al. Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs. Cephalalgia 17(8), 833-842 (1997).
46. Razzaque Z, Heald MA, Pickard JD et al. Vasoconstriction in human isolated middle meningeal arteries: determining the contribution of 5-HT1B- and 5-HT1F-receptor activation. Br. J. Clin. Pharmacol. 47(1), 75-82 (1999).
47. Buzzi MG, Moskowitz MA The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br. J. Pharmacol. 99(1), 202-206 (1990).
48. Longmore J, Boulanger CM, Desta B, Hill R.G., Schofield WN, Taylor AA. 5-HT1D receptor agonists and human coronary artery reactivity in vitro: crossover comparisons of 5-HT and sumatriptan with rizatriptan and L-741,519. Br. J. Clin. Pharmacol. 42(4), 431-441 (1996).
49. Longmore J, Hargreaves RJ, Boulanger CM et al. Comparison of the vasoconstrictor properties of the 5-HT1D-receptor agonists rizatriptan (MK-462) and sumatriptan in human isolated coronary artery: outcome of two independent studies using different experimental protocols. Funct. Neurol. 12(1), 3-9 (1997).
50. Nilsson T, Longmore J, Shaw D et al. Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques. Eur. J. Pharmacol. 372(1), 49-56 (1999).
51. Gupta P, Brown D, Butler P et al. The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective inhibitor of neurogenic inflammation. Br. J. Pharmacol. 116(5), 2385-2390 (1995).
52. Lee WS, Moskowitz MA Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638 exhibit enhanced potency against neurogenic inflammation in dura mater. Brain Res. 626(1-2), 303-305 (1993).
53. Giles H, Honey A, Edvinsson L., Selwood D, Cambridge D, Martin GR Pre-clinical pharmacology of 4991w93, a potent inhibitor of neurogenic plasma protein extravasation. Cephalalgia 19, 402 (1999).
54. Earl NL, McDonald SA, Lowry MT Efficacy and tolerability of the neurogenic inflammation inhibitor, 4991W93 in the acute treatment of migraine. Cephalalgia 19, 357 (1999).
55. Roon KI, Olesen J, Diener HC et al. No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials. Ann. Neurol. 47(2), 238-241 (2000).
56. Harriott AM, Gold MS Serotonin type 1D receptors (5HTR) are differentially distributed in nerve fibres innervating craniofacial tissues. Cephalalgia 28(9), 933-944 (2008).
57. Ma QP. Co-localization of 5-HT(1B/1D/1F) receptors and glutamate in trigeminal ganglia in rats. Neuroreport 12(8), 1589-1591 (2001).
58. Ma QP, Hill R, Sirinathsinghji D. Colocalization of CGRP with 5-HT1B/1D receptors and substance P in trigeminal ganglion neurons in rats. Eur. J. Neurosci. 13(11), 2099-2104 (2001).
59. Smith D, Shaw D, Hopkins R et al. Development and characterisation of human 5-HT1B- or 5-HT1D-receptor specific antibodies as unique research tools. J. Neurosci. Methods 80(2), 155-161 (1998).
60. Smith D, Hill RG, Edvinsson L, Longmore J. An immunocytochemical investigation of human trigeminal nucleus caudalis: CGRP, substance P and 5-HT1D-receptor immunoreactivities are expressed by trigeminal sensory fibres. Cephalalgia 22(6), 424-431 (2002).
61. Castro ME, Pascual J, Romon T., del Arco C, del Olmo E, Pazos A. Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord. Neuropharmacology 36(4-5), 535-542 (1997).
62. Pascual J, Del Arco C, Romon T, Del Olmo E, Pazos A. [3H]Sumatriptan binding sites in human brain: regional-dependent labelling of 5-HT1D and 5-HT1F receptors. Eur. J. Pharmacol. 295(2-3), 271-274 (1996)
63. Mills A, Martin GR Autoradiographic mapping of [3H]sumatriptan binding in cat brain stem and spinal cord. Eur. J. Pharmacol. 280(2), 175-178 (1995).
64. Waeber C, Moskowitz MA [3H] sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study. Naunyn. Schmiedebergs Arch. Pharmacol. 352(3), 263-275 (1995).
65. Goadsby PJ, Knight YE Direct evidence for central sites of action of zolmitriptan (311C90): an autoradiographic study in cat [see comments]. Cephalalgia 17(3), 153-158 (1997).
66. Goadsby PJ, Hoskin KL Differential effects of low dose CP122,288 and eletriptan on Fos expression due to stimulation of the superior sagittal sinus in cat. Pain 82(1), 15-22 (1999).
67. Goadsby PJ, Knight YE Inhibition of trigeminal neurones after intravenous administration of naratriptan through an action at 5-hydroxy-tryptamine (5-HT(1B/1D)) receptors. Br. J. Pharmacol. 122(5), 918-922 (1997).
68. Cumberbatch MJ, Hill RG, Hargreaves RJ Differential effects of the 5HT1B/1D receptor agonist naratriptan on trigeminal versus spinal nociceptive responses. Cephalalgia 18(10), 659-663 (1998).
69. Goadsby PJ, Hoskin KL Inhibition of trigeminal neurons by intravenous administration of the serotonin (5HT)1B/D receptor agonist zolmitriptan (311C90): are brain stem sites therapeutic target in migraine? Pain 67(2-3), 355-359 (1996).
70. Cumberbatch MJ, Hill RG, Hargreaves RJ Rizatriptan has central antinociceptive effects against durally evoked responses. Eur. J. Pharmacol. 328(1), 37-40 (1997).
71. Cumberbatch MJ, Hill RG, Hargreaves RJ The effects of 5-HT1A, 5-HT1B and 5-HT1D receptor agonists on trigeminal nociceptive neurotransmission in anaesthetized rats. Eur. J. Pharmacol. 362(1), 43-46 (1998).
72. Kaube H, Hoskin KL, Goadsby PJ Inhibition by sumatriptan of central trigeminal neurones only after blood-brain barrier disruption. Br. J. Pharmacol. 109(3), 788-792 (1993).
73. Levy D, Jakubowski M, Burstein R. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists. Proc. Natl Acad. Sci. USA 101(12), 4274-4279 (2004).
74. Burstein R, Jakubowski M. Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann. Neurol. 55(1), 27-36 (2004).
75. Cutrer FM, Yu XJ, Ayata G, Moskowitz M.A., Waeber C. Effects of PNU-109,291, a selective 5-HT1D receptor agonist, on electrically induced dural plasma extravasation and capsaicin-evoked c-fos immunoreactivity within trigeminal nucleus caudalis. Neuropharmacology 38(7), 1043-1053 (1999).
76. Gomez-Mancilla B., Cutler NR, Leibowitz MT et al. Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with acute migraine. Cephalalgia 21(7), 727-732 (2001).
77. Storer RJ, Goadsby PJ Microiontophoretic application of serotonin (5HT)1B/1D agonists inhibits trigeminal cell firing in the cat. Brain 120(Pt 12), 2171-2177 (1997).
78. Goadsby PJ, Akerman S, Storer RJ Evidence for postjunctional serotonin (5-HT1) receptors in the trigeminocervical complex. Ann. Neurol. 50(6), 804-807 (2001).
79. Shields KG, Goadsby PJ Serotonin receptors modulate trigeminovascular responses in ventroposteromedial nucleus of thalamus: a migraine target? Neurobiol. Dis. 23, 491-501 (2006).
80. Pfaffenrath V, Scherzer S. Analgesics and NSAIDs in the treatment of the acute migraine attack. Cephalalgia 15(Suppl 15.), 14-20 (1995).
81. Zeilhofer HU, Brune K. Analgesic strategies beyond the inhibition of cyclooxygenases. Trends Pharmacol. Sci. 27(9), 467-474 (2006).
82. Goadsby PJ, Cittadini E, Burns B., Cohen AS. Trigeminal autonomic cephalalgias-diagnostic and therapeutic developments. Current Opinion in Neurology. 21, 323-330 (2008).
83. Summ O, Andreou AP, Akerman S, Hoffmann J., Goadsby PJ. Effects of indomethacin, naproxen and ibuprofen on no-induced trigeminal firing recorded in the trigeminocervical complex. Cephalalgia 31(S1), 10 (2011).
84. Smith CJ, Zhang Y, Koboldt CM et al. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc. Natl Acad. Sci. USA 95(22), 13313-13318 (1998).
85. Riendeau D, Percival MD, Boyce S et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br. J. Pharmacol. 121(1), 105-117 (1997).
86. Vanegas HN, Schaible HG Prostaglandins and cycloxygenases in the spinal cord. Prog. Neurobiol. 64(4), 327-363 (2001).
87. Myren M, Baun M, Ploug K.B., Jansen-Olesen I, Olesen J, Gupta S. Functional and molecular characterization of prostaglandin E2 dilatory receptors in the rat craniovascular system in relevance to migraine. Cephalalgia 30(9), 1110-1122 (2012).
88. Zhang XC, Kainz V, Jakubowski M., Burstein R, Strassman A, Levy D. Localization of COX-1 and COX-2 in the intracranial dura mater of the rat. Neurosci. Lett. 452(1), 33-36 (2009).
89. Antonova M, Wienecke T, Olesen J., Ashina M. Prostaglandin E2 induces immediate migraine-like attack in migraine patients without aura. Cephalalgia 32(11), 822-833 (2012).
90. Sarchielli P, Alberti A, Codini M., Floridi A, Gallai V. Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in internal jugular vein blood during spontaneous migraine attacks. Cephalalgia 20(10), 907-918 (2000).
91. Wienecke T, Olesen J, Ashina M. Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia 30(2), 179-190 (2010).
92. Zhang XC, Strassman AM, Burstein R, Levy D. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J. Pharmacol. Exp. Ther. 322(2), 806-812 (2007).
93. Jakubowski M, Levy D, Goor-Aryeh I, Collins B., Bajwa Z, Burstein R. Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache 45(7), 850-861 (2005).
94. Levy D, Zhang XC, Jakubowski M, Burstein R. Sensitization of meningeal nociceptors: inhibition by naproxen. Eur. J. Neurosci. 27(4), 917-922 (2008).
95. Bergerot A, Holland PR, Akerman S et al. Animal models of migraine: looking at the component parts of a complex disorder. Eur. J. Neurosci. 24(6), 1517-1534 (2006).
96. Olesen J, Iversen HK, Thomsen LL Nitric oxide supersensitivity: a possible molecular mechanism of migraine pain. Neuroreport 4(8), 1027-1030 (1993).
97. Iversen HK, Olesen J, Tfelt-hansen P. Intravenous Nitroglycerin As an Experimental-Model of Vascular Headache-Basic Characteristics. Pain 38(1), 17-24 (1989).
98. Lassen LH, Haderslev PA, Jacobsen V.B., Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 22(1), 54-61 (2002).
99. Akerman S, Williamson DJ, Kaube H, Goadsby PJ The effect of anti-migraine compounds on nitric oxide-induced dilation of dural meningeal vessels. Eur. J. Pharmacol. 452(2), 223-228 (2002).
100. Summ O, Andreou AP, Akerman S, Goadsby PJ A potential nitrergic mechanism of action for indomethacin, but not other COX inhibitors - relevance to indomethacin-sensitive headaches. J. Headache Pain 11(6), 477-483 (2010).
101. May A, Goadsby PJ The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J. Cereb. Blood Flow Metab. 19(2), 115-127 (1999).
102. Rahmann A, Wienecke T, Hansen J.M., Fahrenkrug J., Olesen J, Ashina M. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 28(3), 226-236 (2008).
103. Tassorelli C, Joseph SA Systemic Nitroglycerin Induces Fos Immunoreactivity in Brain-Stem and Forebrain Structures of the Rat. Brain Res. 682(1-2), 167-181 (1995).
104. Tassorelli C, Greco R, Armentero M.T., Blandini F., Sandrini G, Nappi G. A role for brain cyclooxygenase-2 and prostaglandin-E2 in migraine: effects of nitroglycerin. Int. Rev. Neurobiol. 82, 373-382 (2007).
105. Ellrich J, Schepelmann K, Pawlak M., Messlinger K. Acetylsalicylic acid inhibits meningeal nociception in rat. Pain 81(1-2), 7-14 (1999).
106. Kaube H, Hoskin KL, Goadsby PJ Intravenous acetylsalicylic acid inhibits central trigeminal neurons in the dorsal horn of the upper cervical spinal cord in the cat. Headache 33(10), 541-544 (1993).
107. Jakubowski M, Levy D, Kainz V., Zhang XC, Kosaras B, Burstein R. Sensitization of central trigeminovascular neurons: blockade by intravenous naproxen infusion. Neuroscience 148(2), 573-583 (2007).
108. Olesen J, Diener HC, Husstedt IW et al. Calcitonin gene-related peptide receptor antagonist BIBN4096BS for the acute treatment of migraine. N. Engl. J. Med. 350(11), 1104-1110 (2004).
109. 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 70(16), 1304-1312 (2008).
110. Hewitt DJ, Aurora SK, Dodick DW et al. Randomized controlled trial of the CGRP receptor antagonist, MK-3207, in the acute treatment of migraine. Cephalalgia 31, (2011) (in press).
111. Diener HC, Barbanti P, Dahlof C., Reuter U, Habeck J, Podhorna J. BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia 31(5), 573-584 (2011).
112. Han TH, Blanchard RL, Palcza J et al. Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults. J. Clin. Pharmacol. 50(12), 1367-1376 (2010).
113. Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann. Neurol. 23(2), 193-196 (1988).
114. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann. Neurol. 28(2), 183-187 (1990).
115. Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann. Neurol. 33(1), 48-56 (1993).
116. Zagami AS, Goadsby PJ, Edvinsson L. Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides. Neuropeptides 16(2), 69-75 (1990).
117. 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. 507(3), 1277-1299 (2008).
118. Kurosawa M, Messlinger K, Pawlak M., Schmidt RF. Increase of meningeal blood flow after electrical stimulation of rat dura mater encephali: mediation by calcitonin gene-related peptide. Br. J. Pharmacol. 114(7), 1397-1402 (1995).
119. Williamson DJ, Hargreaves RJ, Hill R.G., Shepheard SL. Intravital microscope studies on the effects of neurokinin agonists and calcitonin gene-related peptide on dural vessel diameter in the anaesthetized rat. Cephalalgia 17(4), 518-524(1997a).
120. Troltzsch M, Denekas T, Messlinger K. The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS reduces neurogenic increases in dural blood flow. Eur. J. Pharmacol. 562(1-2), 103-110 (2007).
121. Williamson DJ, Hargreaves RJ, Hill R.G., Shepheard SL. Sumatriptan inhibits neurogenic vasodilation of dural blood vessels in the anaesthetized rat-intravital microscope studies. Cephalalgia 17(4), 525-531 (1997b).
122. Levy D, Burstein R, Strassman AM Calcitonin gene-related peptide does not excite or sensitize meningeal nociceptors: implications for the pathophysiology of migraine. Ann. Neurol. 58(5), 698-705 (2005).
123. Cumberbatch MJ, Williamson DJ, Mason G.S., Hill RG, Hargreaves RJ. Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist. Br. J. Pharmacol. 126(6), 1478-1486 (1999).
124. Fischer MJ, Koulchitsky S, Messlinger K. The nonpeptide calcitonin gene-related peptide receptor antagonist BIBN4096BS lowers the activity of neurons with meningeal input in the rat spinal trigeminal nucleus. J. Neurosci. 25(25), 5877-5883 (2005).
125. Storer RJ, Akerman S, Goadsby PJ Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Br. J. Pharmacol. 142(7), 1171-1181 (2004).
126. Summ O, Charbit AR, Andreou A.P., Goadsby PJ. Modulation of nocioceptive transmission with calcitonin gene-related peptide receptor antagonists in the thalamus. Brain 133(9), 2540-2548 (2010).
127. Zeller J, Poulsen KT, Sutton JE et al. CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat. Br. J. Pharmacol. 155(7), 1093-1103 (2008).
128. Juhl L, Edvinsson L, Olesen J., Jansen-Olesen I. Effect of two novel CGRP-binding compounds in a closed cranial window rat model. Eur. J. Pharmacol. 567(1-2), 117-124 (2007).
129. Brandes JL, Jacobs D, Neto W., Bhattacharaya S. Topiramate in the prevention of migraine headache: a randomized, double-blind, placebo-controlled, parallel study. Neurology 60(Suppl. 1), A238 (2003).
130. Diener HC, Tfelt-Hansen P, Dahlof C et al. Topiramate in migraine prophylaxis-results from a placebo-controlled trial with propranolol as an active control. J. Neurol. 251(8), 943-950 (2004).
131. Edwards KR, Potter DL, Wu S.C., Kamin M., Hulihan J. Topiramate in the preventive treatment of episodic migraine: a combined analysis from pilot, double-blind, placebo-controlled trials. CNS Spectr. 8(6), 428-432 (2003).
132. Silberstein SD, Neto W, Schmitt J., Jacobs D. Topiramate in migraine prevention: results of a large controlled trial. Arch. Neurol. 61(4), 490-495 (2004).
133. Shank RP, Gardocki JF, Streeter A.J., Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 41(Suppl. 1), S3-S9 (2000).
134. Dalkara T, Nozari A, Moskowitz MA Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol. 9(3), 309-317 (2010).
135. Eikermann-Haerter K., Moskowitz MA Animal models of migraine headache and aura. Curr. Opin. Neurol. 21(3), 294-300 (2008).
136. Eikermann-Haerter K., Ayata C. Cortical spreading depression and migraine. Curr. Neurol. Neurosci. Rep. 10(3), 167-173 (2010).
137. Wolthausen J, Sternberg S, Gerloff C., May A. Are cortical spreading depression and headache in migraine causally linked? Cephalalgia 29(2), 244-249 (2009).
138. Goadsby PJ. Migraine, aura and cortical spreading depression: why are we still talking about it? Ann. Neurol. 49, 4-6 (2001).
139. Ayata C. Cortical spreading depression triggers migraine attack: pro. Headache 50(4), 725-730 (2010).
140. Charles A. Does cortical spreading depression initiate a migraine attack? Maybe not. Headache 50(4), 731-733 (2010).
141. Leao AAP. Spreading depression of activity in cerebral cortex. J. Neurophysiol. 7, 359-390 (1944).
142. Leao AAP. Pial circulation and spreading activity in the cerebral cortex. J. Neurophysiol. 7, 391-396 (1944).
143. Akerman S, Goadsby PJ Topiramate inhibits cortical spreading depression in rat and cat: impact in migraine aura. Neuroreport 16(12), 1383-1387 (2005).
144. Ayata C, Jin H, Kudo C., Dalkara T, Moskowitz MA. Suppression of cortical spreading depression in migraine prophylaxis. Ann. Neurol. 59(4), 652-661 (2006).
145. Akerman S, Goadsby PJ Topiramate inhibits trigeminovascular activation: an intravital microscopy study. Br. J. Pharmacol. 146(1), 7-14 (2005).
146. Storer RJ, Goadsby PJ Topiramate inhibits trigeminovascular neurons in the cat. Cephalalgia 24(12), 1049-1056 (2004).
147. Andreou AP, Goadsby PJ Topiramate in the treatment of migraine: a kainate (glutamate) receptor antagonist within the trigeminothalamic pathway. Cephalalgia 31(13), 1343-1358 (2011).
148. Knight YE, Bartsch T, Goadsby PJ Trigeminal antinociception induced by bicuculline in the periaqueductal gray (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat. Neurosci. Lett. 336(2), 113-116 (2003).
149. Tfelt-Hansen P., De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs 60(6), 1259-1287 (2000).
150. Bouchelet I, Case B, Olivier A., Hamel E. No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery. Br. J. Pharmacol. 129(3), 501-508 (2000).
151. Bouchelet I, Cohen Z, Case B., Seguela P, Hamel E. Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels. Mol. Pharmacol. 50(2), 219-223 (1996).
152. Classey JD, Bartsch T, Goadsby PJ Distribution of 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor expression in rat trigeminal and dorsal root ganglia neurons: relevance to the selective anti-migraine effect of triptans. Brain Res. 1361, 76-85 (2010).
153. Amrutkar DV, Ploug KB, Hay-Schmidt A, Porreca F., Olesen J, Jansen-Olesen I. mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system. Pain 153(4), 830-838 (2012).
154. Bruinvels AT, Landwehrmeyer B, Gustafson EL et al. Localization of 5-HT1B, 5-HT1D alpha, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. Neuropharmacology 33(3-4), 367-386 (1994).
155. Johnson KW, Schaus JM, Durkin MM et al. 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs. Neuroreport 8(9-10), 2237-2240 (1997).
156. Phebus LA, Johnson KW, Zgombick JM et al. Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine. Life Sci. 61(21), 2117-2126 (1997).
157. Nelson DL, Phebus LA, Johnson KW et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia 30(10), 1159-1169 (2010).
158. Mitsikostas DD, Sanchez del Rio M, Waeber C. 5-Hydroxytryptamine(1B/1D) and 5-hydroxytryptamine1F receptors inhibit capsaicin-induced c-fos immunoreactivity within mouse trigeminal nucleus caudalis. Cephalalgia 22(5), 384-394 (2002).
159. Mitsikostas DD, Sanchez del Rio M, Moskowitz MA, Waeber C. Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis. Eur. J. Pharmacol. 369(3), 271-277 (1999).
160. Goadsby PJ, Classey JD Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F receptor inhibitory effects on trigeminal neurons with craniovascular input. Neuroscience 122(2), 491-498 (2003).
161. Shepheard S, Edvinsson L, Cumberbatch M et al. Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370. Cephalalgia 19(10), 851-858 (1999).
162. Storer RJ, Goadsby PJ 5-HT1F agonists inhibit nociceptive transmission at the trigeminocervical complex. Cephalalgia 31(S1), 9-10 (2011).
163. Goldstein DJ, Roon KI, Offen WW et al. Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial. Lancet 358(9289), 1230-1234 (2001).
164. Farkkila M, Diener HC, Geraud G et al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol. 11(5), 405-413 (2012).
165. Ferrari MD, Farkkila M, Reuter U et al. Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan-a randomised proof-of-concept trial. Cephalalgia 30(10), 1170-1178 (2010).
166. Andreou AP, Goadsby PJ Therapeutic potential of novel glutamate receptor antagonists in migraine. Expert Opin. Investig. Drugs 18(6), 789-803 (2009).
167. Storer RJ, Goadsby PJ Trigeminovascular nociceptive transmission involves N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors. Neuroscience 90(4), 1371-1376 (1999).
168. Classey JD, Knight YE, Goadsby PJ The NMDA receptor antagonist MK-801 reduces Fos-like immunoreactivity within the trigeminocervical complex following superior sagittal sinus stimulation in the cat. Brain Res. 907(1-2), 117-124 (2001).
169. Goadsby PJ, Classey JD Glutamatergic transmission in the trigeminal nucleus assessed with local blood flow. Brain Res. 875(1-2), 6 (2000).
170. Charles A, Flippen C, Romero Reyes M, Brennan KC. Memantine for prevention of migraine: a retrospective study of 60 cases. J Headache Pain 8(4), 248-250 (2007).
171. Andreou AP, Holland PR, Goadsby PJ Activation of iGluR5 kainate receptors inhibits neurogenic dural vasodilatation in an animal model of trigeminovascular activation. Br. J. Pharmacol. 157(3), 464-473 (2009).
172. Andreou AP, Holland PR, Goadsby PJ Pre- and post-synaptic involvement of GluR5 kainate receptor in the trigeminovascular nociceptive processing. Cephalalgia 27, 605 (2007).
173. Weiss B, Alt A, Ogden AM et al. Pharmacological characterization of the competitive GLUK5 receptor antagonist decahydroisoquinoline LY466195 in vitro and in vivo. J. Pharmacol. Exp. Ther. 318(2), 772-781 (2006).
174. Johnson KW, Nisenbaum ES, Johnson MP et al. Innovative drug development for headache disorders: glutamate. In: Innovative drug development for headache disorders. Olesen J, Ramadan NM, (Eds). Oxford University Press, London, 185-194 (2008).
175. Sang CN, Ramadan NM, Wallihan RG et al. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia 24(7), 596-602 (2004).
176. Holland P, Goadsby PJ The hypothalamic orexinergic system: pain and primary headaches. Headache 47(6), 951-962 (2007).
177. Sarchielli P, Rainero I, Coppola F et al. Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine and medication-overuse headache: findings from cerebrospinal fluid. Cephalalgia 28(7), 714-722 (2008).
178. Holland PR, Akerman S, Goadsby PJ Orexin 1 receptor activation attenuates neurogenic dural vasodilation in an animal model of trigeminovascular nociception. J. Pharmacol. Exp. Ther. 315(3), 1380-1385 (2005).
179. Holland PR, Akerman S, Goadsby PJ Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur. J. Neurosci. 24(10), 2825-2833 (2006).
180. Herring WJ, Snyder E, Budd K et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology 79(23), 2265-2274 (2012).
181. Sun H, Kennedy WP, Wilbraham D et al. Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sleep 36(2), 259-267 (2013).
182. Hoever P, Hay J, Rad M., Cavallaro M, van Gerven JM, Dingemanse J. Tolerability, pharmacokinetics, and pharmacodynamics of single-dose almorexant, an orexin receptor antagonist, in healthy elderly subjects. J. Clin. Psychopharmacol. 33(3), 363-370 (2013).
183. Black SW, Morairty SR, Fisher S.P., Chen TM, Warrier DR, Kilduff TS. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep 36(3), 325-336 (2013).
184. Strecker T, Dux M, Messlinger K. Increase in meningeal blood flow by nitric oxide-interaction with calcitonin gene-related peptide receptor and prostaglandin synthesis inhibition. Cephalalgia 22(3), 233-241 (2002).
185. Koulchitsky S, Fischer MJ, De Col R, Schlechtweg PM, Messlinger K. Biphasic response to nitric oxide of spinal trigeminal neurons with meningeal input in rat-possible implications for the pathophysiology of headaches. J. Neurophysiol. 92(3), 1320-1328 (2004).
186. Lambert GA, Hoskin KL, Zagami AS Nitrergic and glutamatergic neuronal mechanisms at the trigeminovascular first-order synapse. Neuropharmacology 47(1), 92-105 (2004).
187. Afridi SK, Matharu MS, Lee L et al. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain 128(Pt 4), 932-939 (2005).
188. Pardutz A, Multon S, Malgrange B., Parducz A, Vecsei L, Schoenen J. Effect of systemic nitroglycerin on CGRP and 5-HT afferents to rat caudal spinal trigeminal nucleus and its modulation by estrogen. Eur. J. Neurosci. 15(11), 1803-1809 (2002).
189. Dieterle A, Fischer MJ, Link A.S., Neuhuber WL, Messlinger K. Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor. Cephalalgia 31(1), 31-42 (2011).
190. Pardutz A, Krizbai I, Multon S., Vecsei L, Schoenen J. Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis. Neuroreport 11(14), 3071-3075 (2000).
191. Akerman S, Williamson DJ, Kaube H, Goadsby PJ Nitric oxide synthase inhibitors can antagonize neurogenic and calcitonin gene-related peptide induced dilation of dural meningeal vessels. Br. J. Pharmacol. 137(1), 62-68 (2002).
192. Hoskin KL, Bulmer DCE, Lasalandra M, Goadsby PJ Fos expression in the trigeminocervical complex is reduced by NOS inhibition. Cephalalgia 19(4), 394-394 (1999).
193. Offenhauser N, Zinck T, Hoffmann J et al. CGRP release and c-fos expression within trigeminal nucleus caudalis of the rat following glyceryltrinitrate infusion. Cephalalgia 25(3), 225-236 (2005).
194. Lassen LH, Olesen J. Nitric Oxide Synthase activation in inhibition in migraine. In: Headache Pathogenesis: Monoamines, Neuropeptides, Purines and Nitric Oxide. Olesen J, Edvinsson L (Eds). Lippincott-Raven, Philadelphia, 247-255 (1997).
195. Hoivik HO, Laurijssens BE, Harnisch LO et al. Lack of efficacy of the selective iNOS inhibitor GW274150 in prophylaxis of migraine headache. Cephalalgia 30(12), 1458-1467 (2010).
196. Hoffmann J, Goadsby PJ New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors. Curr. Treat Options Neurol. 14(1), 50-59 (2012).
197. Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. Lancet Neurol. 3(8), 475-483 (2004).
198. Bigal ME, Serrano D, Buse D., Scher A, Stewart WF, Lipton RB Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 48, 1157-1168 (2008).
199. Markowitz S, Saito K, Moskowitz MA Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J. Neurosci. 7(12), 4129-4136 (1987).
200. Markowitz S, Saito K, Moskowitz MA Neurogenically mediated plasma extravasation in dura mater: effect of ergot alkaloids. A possible mechanism of action in vascular headache. Cephalalgia 8(2), 83-91 (1988).
201. Goldstein DJ, Offen WW, Klein EG et al. Lanepitant, an NK-1 antagonist, in migraine prevention. Cephalalgia 21(2), 102-106 (2001).
202. Goldstein DJ, Wang O, Saper J.R., Stoltz R., Silberstein SD, Mathew NT. Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study. Cephalalgia 17(7), 785-790 (1997).
203. Peroutka SJ. Neurogenic inflammation and migraine: implications for the therapeutics. Mol. Interv. 5(5), 304-311 (2005).
204. Akerman S, Holland PR, Goadsby PJ Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na(+) ion channel blockade. Brain Res. 1229, 27-36 (2008).
205. Holland PR, Akerman S, Goadsby PJ Cortical spreading depression-associated cerebral blood flow changes induced by mechanical stimulation are modulated by AMPA and GABA receptors. Cephalalgia 30(5), 519-527 (2010).
206. Richter F, Ebersberger A, Schaible H-G. Blockade of voltage-gated calcium channels in rat inhibits repetitive cortical spreading depression. Neurosci. Lett. 334, 123-126 (2002).
207. Akerman S, Williamson DJ, Goadsby PJ Voltage-dependent calcium channels are involved in neurogenic dural vasodilatation via a presynaptic transmitter release mechanism. Br. J. Pharmacol. 140(3), 558-566 (2003).
208. Shields KG, Storer RJ, Akerman S, Goadsby PJ Calcium channels modulate nociceptive transmission in the trigeminal nucleus of the cat. Neuroscience 135(1), 203-212 (2005).
209. Storer RJ, Akerman S, Goadsby PJ GABA receptors modulate trigeminovascular nociceptive neurotransmission in the trigeminocervical complex. Br. J. Pharmacol. 134(4), 896-904 (2001).