The neurobiology of migraine.
The understanding of migraine has moved well beyond its traditional characterization as a "vascular headache." In considering the basic neurobiology of migraine, it is important to begin with the concept of migraine as not merely a headache, but rather a heterogeneous array of episodic symptoms. Among the array of phenomena experienced by migraine patients are visual disturbances, nausea, cognitive dysfunction, fatigue, and sensitivity to light, sound, smell, and touch. These symptoms may occur independently or in any combination, and in some patients occur even in the absence of headache. The diversity and variability of symptoms experienced by migraine patients belies a complex neurobiology, involving multiple cellular, neurochemical, and neurophysiological processes occurring at multiple neuroanatomical sites. Migraine is a multifaceted neurobiological phenomenon that involves activation of diverse neurochemical and cellular signaling pathways in multiple regions of the brain. Propagated waves of cellular activity in the cortex, possibly involving distinct glial and vascular signaling mechanisms, can occur along with activation of brainstem centers and nociceptive pathways. Whether different brain regions become involved in a linear sequence, or as parallel processes, is uncertain. The modulation of brain signaling by genetic factors, and by sex and sex hormones, provides important clues regarding the fundamental mechanisms by which migraine is initiated and sustained. Each of these mechanisms may represent distinct therapeutic targets for this complex and commonly disabling disorder.
Charles
Andrew
A
Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. acharles@ucla.edu
Brennan
K C
KC
D001921:Brain; D001933:Brain Stem; D006261:Headache; D006801:Humans; D008881:Migraine Disorders / Q000628:therapy; D009446:Neurobiology
Nat Genet. 2003 Feb;33(2):192-6
12539047
Brain. 2003 Jan;126(Pt 1):241-7
12477710
Brain. 2002 May;125(Pt 5):976-84
11960888
Neurol Sci. 2006 May;27 Suppl 2:S77-81
16688634
Cephalalgia. 2004 Feb;24(2):99-109
14728705
Brain Res. 1987 Dec 29;437(2):360-4
3435842
Brain Res. 1989 Jan 2;476(1):71-7
2914215
J Cereb Blood Flow Metab. 2004 Oct;24(10):1172-82
15529018
Cephalalgia. 2006 Jul;26(7):865-70
16776703
J Pharmacol Exp Ther. 2007 May;321(2):564-72
17267580
Nature. 1996 Dec 12;384(6609):560-4
8955268
J Neurophysiol. 2007 Jun;97(6):4143-51
17329631
Pain. 2001 Feb 15;90(3):227-231
11207394
Brain. 1996 Feb;119 ( Pt 1):249-56
8624686
Cephalalgia. 1989 Jun;9(2):107-18
2743409
Brain. 1994 Jun;117 ( Pt 3):427-34
7518321
Headache. 2001 Jul-Aug;41(7):629-37
11554950
Nat Med. 2002 Feb;8(2):136-42
11821897
Cephalalgia. 2003 May;23(4):258-63
12716342
Arch Neurol. 1999 May;56(5):548-54
10328249
N Engl J Med. 1994 Dec 22;331(25):1689-92
7969360
Neuron. 1991 Jun;6(6):983-92
1675864
Ann Neurol. 2007 Jun;61(6):603-6
17474110
J Comp Neurol. 2007 Nov 20;505(3):268-91
17879271
Lancet. 2005 Jul 30-Aug 5;366(9483):371-7
16054936
Headache. 2007 Nov-Dec;47(10):1418-26
18052951
Neurology. 2002 Apr 23;58(8):1308-10
11971111
Headache. 2006 Jul-Aug;46(7):1095-107
16866714
J Neurosci. 2003 Oct 29;23(30):9888-96
14586018
Neurobiol Dis. 2006 Sep;23(3):491-501
16875831
Cephalalgia. 2007 Dec;27(12):1454-6
18034689
J Neurophysiol. 2002 Dec;88(6):3021-31
12466427
Lancet. 2001 Mar 31;357(9261):1016-7
11293599
J Clin Invest. 2004 May;113(10):1447-55
15146242
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4687-92
11287655
Nat Neurosci. 2006 Feb;9(2):260-7
16388306
Headache. 2007 Apr;47(4):552-63
17445105
Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11106-11
16037212
Headache. 1999 Jul-Aug;39(7):469-76
11279929
Physiol Rev. 2006 Jul;86(3):1009-31
16816144
Nature. 2004 Sep 9;431(7005):195-9
15356633
Neurology. 2002 Jul 9;59(1):72-8
12105310
Annu Rev Physiol. 1999;61:835-56
10099712
Ann Neurol. 1990 Dec;28(6):791-8
2285266
Cell. 1996 Nov 1;87(3):543-52
8898206
Headache. 1993 Sep;33(8):452-5
8262789
Brain. 2008 Aug;131(Pt 8):2192-200
18502781
Headache. 2007 Jun;47(6):852-4
17578534
Nat Neurosci. 2006 Nov;9(11):1397-1403
17013381
Glia. 1998 Sep;24(1):39-49
9700488
J Neurophysiol. 1947 Nov;10(6):409-14
20268874
J Neurosci. 1998 Sep 15;18(18):7189-99
9736642
Headache. 2005 Nov-Dec;45(10):1394-9
16324172
J Neurosci. 2007 Apr 11;27(15):4036-44
17428981
J Neurosci. 1999 Jan 15;19(2):520-8
9880572
Rev Neurol (Paris). 2005 Jul;161(6-7):666-70
16141953
J Neurophysiol. 2006 Mar;95(3):1298-306
16492942
Nat Genet. 2007 Sep;39(9):1068-70
17660820
Headache. 2007 Jul-Aug;47(7):996-1003; discussion 1004-7
17635590
Nat Med. 1995 Jul;1(7):658-60
7585147
Neuron. 2004 Mar 4;41(5):701-10
15003170
Brain. 2005 Apr;128(Pt 4):932-9
15705611
Cephalalgia. 2005 Mar;25(3):225-36
15689199
Hippocampus. 2004;14(3):356-67
15132435
Nat Neurosci. 2003 Jan;6(1):43-50
12469126
J Headache Pain. 2006 Dec;7(6):377-88
17164990
Novartis Found Symp. 2006;276:208-17; discussion 217-21, 233-7, 275-81
16805432
Eur J Hum Genet. 2006 May;14(5):555-60
16538223
Cephalalgia. 2001 Mar;21(2):96-101
11422090
J Neuroimmune Pharmacol. 2006 Sep;1(3):223-36
18040800
Headache. 1987 Sep;27(8):416-20
3667258
Cephalalgia. 2002 Mar;22(2):107-11
11972577
Ann Neurol. 1998 Nov;44(5):731-9
9818928
Pain. 1996 Oct;67(2-3):355-9
8951929
Lancet. 1977 May 14;1(8020):1034-6
67489
Neurosci Lett. 2004 Aug 19;366(3):241-4
15288426
Neurology. 2005 Jun 28;64(12):2145-7
15985592