BRAIN and NERVE－神経研究の進歩73巻4号

2021年04月発行

特集 片頭痛・群発頭痛治療の新たな夜明け

片頭痛のメカニズム—予兆とCGRP/CGRP受容体拮抗薬に関連して

著者： 粟木悦子¹ 竹島多賀夫²

所属機関： ¹鳥取県済生会境港総合病院脳神経内科 ²社会医療法人寿会富永病院脳神経内科・頭痛センター

ページ範囲：P.303 - P.313

文献概要

片頭痛の発症メカニズムはいまだ不明である。予兆は一連の片頭痛発作の中で最初に認められる症状であり，その研究は片頭痛発生源解明につながるとして近年あらためて関心が高まっている。特に予兆症状と視床下部との関連が示唆されている。また，片頭痛メカニズムにおけるカルシトニン遺伝子関連ペプチドの役割について，血管拡張，神経性炎症，末梢感作といった末梢作用のみならず，光過敏，中枢感作，皮質拡延性抑制などと関連する中枢作用についても多くの知見が集まりつつある。

参考文献

1)GBD 2016 Disease and Injury Incidence and Prevalence Collaborators: Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390: 1211-1259, 2017

2)日本頭痛学会・国際頭痛分類委員会（訳）: 国際頭痛分類, 第3版. 医学書院, 東京, 2018

3)永田栄一郎: 片頭痛の病態に関する最新の知見. 臨床神経60: 20-26, 2020

4)Mirza AF, Mo J, Holt JL, Kairalla JA, Heft MW, et al: Is there a relationship between throbbing pain and arterial pulsations? J Neurosci 32: 7572-7576, 2012

5)Amin FM, Asghar MS, Hougaard A, Hansen AE, Larsen VA, et al: Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol 12: 454-461, 2013

6)Lashley KS: Patterns of cerebral integration indicated by the scotomas of migraine. Arch Neurol Psychiatry 46: 331-339, 1941

7)Leão AAP: Further observations on the spreading depression of activity in the cerebral cortex. J Neurophysiol 10: 409-414, 1947

8)Olesen J, Larsen B, Lauritzen M: Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 9: 344-352, 1981

9)Hadjikhani N, del Rio MS, Wu O, Schwartz D, Bakker D, et al: Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A 98: 4687-4692, 2001

10)Moskowitz MA: The neurobiology of vascular head pain. Ann Neurol 16: 157-168, 1984

11)Karatas H, Erdener SE, Gursoy-Ozdemir Y, Lule S, Eren-Koçak E, et al: Spreading depression triggers headache by activating neuronal Panx1 channels. Science 339: 1092-1095, 2013

12)Gallai V, Sarchielli P, Floridi A, Franceschini M, Codini M, et al: Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia 15: 384-390, 1995

13)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: 4129-4136, 1987

14)May A, Shepheard S, Wessing A, Hargreaves RJ, Goadsby PJ, et al: Retinal plasma extravasation can be evoked by trigeminal stimulation in rat but does not occur during migraine attacks. Brain 121: 1231-1237, 1998

15)Goldstein DJ, Offen WW, Klein EG, Phebus LA, Hipskind P, et al: Lanepitant, an NK-1 antagonist, in migraine prevention. Cephalalgia 21: 102-106, 2001

16)Earl NL, McDonald SA, Lowy MT; 4991W93 Investigator Group: Efficacy and tolerability of the neurogenic inflammation inhibitor, 4991W93, in the acute treatment of migraine. Cephalalgia 19: 357, 1999

17)Roon KI, Olesen J, Diener HC, Ellis P, Hettiarachchi J, 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: 238-241, 2000

18)Maniyar FH, Sprenger T, Monteith T, Schankin CJ, Goadsby PJ: The premonitory phase of migraine--what can we learn from it? Headache 55: 609-620, 2015

19)Quintela E, Castillo J, Muñoz P, Pascual J: Premonitory and resolution symptoms in migraine: a prospective study in 100 unselected patients. Cephalalgia 26: 1051-1060, 2006

20)Giffin NJ, Ruggiero L, Lipton RB, Silberstein SD, Tvedskov JF, et al: Premonitory symptoms in migraine: an electronic diary study. Neurology 60: 935-940, 2003

21)Karsan N, Bose P, Goadsby PJ: The migraine premonitory phase. Continuum (Minneap Minn) 24: 996-1008, 2018

22)Karsan N, Bose P, Goadsby PJ: The phenotype of premonitory symptoms and migraine headache triggered with nitroglycerin. Cephalalgia 36(1S): 53-54, 2016

23)Kropp P, Gerber WD: Prediction of migraine attacks using a slow cortical potential, the contingent negative variation. Neurosci Lett 257: 73-76, 1998

24)Evers S, Quibeldey F, Grotemeyer KH, Suhr B, Husstedt IW: Dynamic changes of cognitive habituation and serotonin metabolism during the migraine interval. Cephalalgia 19: 485-491, 1999

25)Sand T, Zhitniy N, White LR, Stovner LJ: Visual evoked potential latency, amplitude and habituation in migraine: a longitudinal study. Clin Neurophysiol 119: 1020-1027, 2008

26)Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ: Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Brain 137: 232-241, 2014

27)Schulte LH, May A: The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain 139: 1987-1993, 2016

28)Strother LC, Srikiatkhachorn A, Supronsinchai W: Targeted orexin and hypothalamic neuropeptides for migraine. Neurotherapeutics 15: 377-390, 2018

29)Levy MJ, Matharu MS, Bhola R, Meeran K, Goadsby PJ: Octreotide is not effective in the acute treatment of migraine. Cephalalgia 25: 48-55, 2005

30)Rustichelli C, Lo Castro F, Baraldi C, Ferrari A: Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review. Expert Opin Investig Drugs 29: 1269-1275, 2020

31)Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, et al: Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304: 129-135, 1983

32)Russell FA, King R, Smillie SJ, Kodji X, Brain SD: Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev 94: 1099-1142, 2014

33)Hay DL, Garelja ML, Poyner DR, Walker CS: Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25. Br J Pharmacol 175: 3-17, 2018

34)Goadsby PJ, Edvinsson L, Ekman R: Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 28: 183-187, 1990

35)Ho TW, Edvinsson L, Goadsby PJ: CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol 6: 573-582, 2010

36)Tfelt-Hansen P, Le H: Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? a review. J Headache Pain 10:137-143, 2009

37)Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J: Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain 86: 133-138, 2000

38)Goadsby PJ, Edvinsson L: The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 33: 48-56, 1993

39)Juhasz G, Zsombok T, Modos EA, Olajos S, Jakab B, et al: No-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. Pain 106: 461-470, 2003

40)Hansen JM, Hauge AW, Olesen J, Ashina M: Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia 30: 1179-1186, 2010

41)Russo AF: Calcitonin gene-related peptide (CGRP): a new target for migraine. Annu Rev Pharmacol Toxicol 55: 533-552, 2015

42)Recober A, Kuburas A, Zhang Z, Wemmie JA, Anderson MG, et al: Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine. J. Neurosci 29: 8798-8804, 2009

43)Zhang Z, Winborn CS, Marquez de Prado B, Russo AF: Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J. Neurosci 27: 2693-2703, 2007

44)Lennerz JK, Ruhle V, Ceppa EP, Neuhuber WL, Bunnett NW, 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: 1277-1299, 2008

45)Thalakoti S, Patil VV, Damodaram S, Vause CV, Langford LE, et al: Neuron-glia signaling in trigeminal ganglion: implications for migraine pathology. Headache 47: 1008-1023, 2007

46)Giniatullin R, Nistri A, Fabbretti E: Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the migraine mediators CGRP and NGF. Mol Neurobiol 37: 83-90, 2008

47)Recober A, Kaiser EA, Kuburas A, Russo AF: Induction of multiple photophobic behaviors in a transgenic mouse sensitized to CGRP. Neuropharmacology 58: 156-165, 2010

48)Kaiser EA, Kuburas A, Recober A, Russo AF: Modulation of CGRP-induced light aversion in wild-type mice by a 5-HT (1B/D) agonist. J Neurosci 32: 15439-15449, 2012

49)Russo AF, Recober A: Unanswered questions in headache: so what is photophobia, anyway? Headache 53: 1677-1678, 2013

50)Russo AF, Kuburas A, Kaiser EA, Raddant AC, Recober A: A potential preclinical migraine model: CGRP-sensitized mice. Mol Cell Pharmacol 1: 264-270, 2009

51)Gu XL, Yu LC: The colocalization of CGRP receptor and AMPA receptor in the spinal dorsal horn neuron of rat: a morphological and electrophysiological study. Neurosci Lett 414: 237-241, 2007

52)Seybold VS: The role of peptides in central sensitization. Handb Exp Pharmacol 194: 451-491, 2009

53)Marquez de Prado B, Hammond DL, Russo AF: Genetic enhancement of calcitonin gene-related Peptide-induced central sensitization to mechanical stimuli in mice. J Pain 10: 992-1000, 2009

54)Levy D: Migraine pain and nociceptor activation--where do we stand? Headache 50: 909-916, 2010

55)Viggiano A, Viggiano E, Valentino I, Monda M, Viggiano A, et al: Cortical spreading depression affects reactive oxygen species production. Brain Res 1368: 11-18, 2011

56)Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, et al: Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350: 1104-1110, 2004

57)Connor KM, Shapiro RE, Diener HC, Lucas S, Kost J, et al: Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 73: 970-977, 2009

58)Lipton RB, Dodick DW, Ailani J, Lu K, Finnegan M, et al: Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine: the ACHIEVE Ⅱ randomized clinical trial. JAMA 322: 1887-1898, 2019

59)Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, et al: Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet 394: 737-745, 2019

60)Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, et al: A controlled trial of erenumab for episodic migraine. N Engl J Med 377: 2123-2132, 2017

61)Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, et al: Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA 319: 1999-2008, 2018

62)Förderreuther S, Zhang Q, Stauffer VL, Aurora SK, Láinez MJA: Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. J Headache Pain 19: 121, 2018

63)Ashina M, Saper J, Cady R, Schaeffler BA, Biondi DM, et al: Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia 40: 241-254, 2020