complex network of neurotransmission systems underlies the control of the cerebral circulation. Classical neurotransmitters, vasoactive peptides and receptors have been found in cerebral arteries. Central and peripheral structures are also probably involved in the neurogenic control of the cerebral circulation. Vascular and neurotransmission changes reported in vascular headaches suggest that an alteration of the neurogenic control of the brain circulation may be implicated in vascular headaches. In particular, locus coeruleus, which may control the intracerebral adrenergic pathway, can induce vascular changes similar to those of migraine. Moreover, the trigeminal ganglion, which may induce the release of substance P, can change the extracranial and intracranial vasodilator activity. The vascular theory of migraine, proposed by Wolff, is re-evaluated on the grounds of a possible mediation of the vascular responses by neurotransmitters. It is hypothesized that a deficient modulation by enkephalins may cause alterations of locus coeruleus and/or trigeminal ganglion. The problem of pain in vascular headaches is also considered: whether it is of vascular origin or whether it is due to a dysfunction of the central nociceptive pathway. Knowledge of the neurogenic control of the cerebral circulation may be useful in understanding some pathogenetic mechanisms of vascular headaches.
O'BrienMD. Cerebral blood changes in migraine. Headache1971;10:139–43.
2.
LauritzenMOlsenTSLassenNAPaulsonOB. Changes in regional cerebral blood flow during the course of classic migraine attacks. Ann Neurol1983;13:633–41.
3.
DrummondPDLanceJW. Extracranial vascular changes and the source of pain in migraine headache. Ann Neurol1983;13:32–7.
4.
SicuteriF. Headache as the most common disease of the antinociceptive system: analogies with morphine abstinence. In: BonicaJJLiebeskindJCAlbe-FessardDG eds Advances in pain research and therapy. Vol. 3New York: Raven Press, 1979:359–65.
5.
SicuteriF. Vasoneuroactive substances and their implication in vascular pain. Res Clin Stud headache1967;1:6–45.
6.
WolffHG. Headache and other head pain. 2nd edn. New York: Oxford University Press, 1963.
7.
NielsenKCOwmanChSporrongB. Ultra-structure of the autonomic innervation apparatus in main pial arteries of rats and cats. Brain Res1971;27:25–32.
8.
EdvinssonLMacKenzieET. Amine mechanisms in the cerebral circulation. Pharmacol Rev1977;28:275–348.
9.
Chan PalayV. Innervation of cerebral blood vessels by norepinephrine, indoleamine, substance P and neurotensin fibres and the leptomeningeal indoleamine axons: their roles in vasomotor activity and local alterations of brain blood composition. In: OwmanChEdvinssonL eds Neurogenic control of the brain circulation. New York: Pergamon Press, 1977:39–53.
10.
EdvinssonLOwmanCh. Pharmacological characterization of postsynaptic vasomotor receptors in brain vessels. In: OwmanChEdvinssonL eds Neurogenic control of the brain circulation. New York: Pergamon Press, 1977:167–83.
11.
OlesenJ. Effects of circulating monoamines and related substances on rCBF in man. In: HeistadDDMarcusML eds Cerebral blood flow: effects of nerves and neurotransmitters. New York: Elsevier—North Holland1982:183–8.
12.
MacKenzieETPickardJDHardeboJE. Blood brain barrier amines and the cerebral circulation: problems and approaches. In: OwmanChEdvinssonL eds Neurogenic control of the brain circulation. New York: Pergamon Press, 1977:231–43.
13.
HardeboJEEmsonPCFalckPCOwmanChRosengrenE. Enzymes related to monoamine metabolism in brain microvessels. J Neurochem1980;35:1388–93.
14.
EdvinssonLUddmanR. Distribution and effects of noradrenaline, VIP and substance P in cerebral and peripheral blood vessels. In: HeistadDDMarcusML eds Cerebral blood flow: effects of nerves and neurotransmitters. New York: Elsevier—North Holland1982:211–17.
15.
EdvinssonL. Sympathetic control of cerebral circulation. TINS1982;5:425–8.
16.
OwmanChEdvinssonL. Histochemical and pharmacological approach to the investigation of neurotransmitters, with particular regard to the cerebrovascular bed. In: OwmanChEdvinssonL eds Neurogenic control of the brain circulation. New York: Pergamon Press, 1977:15–38.
17.
RaichleMEHartmanBDEichlingJOSharpeLG. Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Nat Acad Sci1975;72:3726–30.
18.
TsubokawaTKatayamaYKondoTUenoYHayashiNMoriyasuN. Changes in local cerebral blood flow and neuronal activity during sensory stimulation in normal and sympathectomized cats. Brain Res1980;190:51–65.
19.
GrubbRLRaichleMEEichlingJO. Peripheral sympathetic regulation of brain water permeability. Brain Res1978;144:204–7.
20.
DuckiesSPBevanJA. Pharmacological characterization of adrenergic receptors of a rabbit cerebral artery in vitro. J Pharmacol Exp Ther1976;197:371–8.
21.
KobayashiHMaoretTFerranteMSpanoPTrabucchiM. Subtypes of β-adrenergic receptors in rat cerebral microvessels. Brain Res1981;220:194–8.
22.
GoadsbyPJLambertGALanceJW. Differential effects on the internal and external carotid circulation of the monkey evoked by locus coeruleus stimulation. Brain Res1982;249:247–54.
23.
LanceJWLambertGAGoadsbyPJDuckworthJW. Brainstem influences on the cephalic circulation: experimental data from cat and monkey of relevance to the mechanism of migraine. Headache1983;23:258–65.
24.
IwayamaTFurnessJBBurnstockG. Dual adrenergic and cholinergic innervation of the cerebral arteries of the rat. Circ Res1970;26:635–46.
25.
BevanJABugaGMFlorenceVMGonsalvesASnowdenA. Distribution of choline acetyltransfer-ase in cerebral and extracerebral cranial arteries of the cat. Circ Res1982;50:470–6.
26.
CuelloACSofroniewMV. The anatomy of the CNS cholinergic neurons. TINS1984;5:74–8.
27.
BevanJABugaGMSnowdenASaidSI. Is the neural vasodilator mechanism to cerebral and extracerebral arteries the same? In: HeistadDDMarcusML eds Cerebral blood flow: effects of nerves and neurotransmitters. New York: Elsevier—North Holland, 1982:421–30.
28.
EdvinssonLFalckBOwmanCh. Possibilities for a cholinergic action on smooth musculature and on sympathetic axons in brain vessels mediated by muscarinic and nicotinic receptors. J Pharmacol Exp Ther1977;200:117–26.
29.
SercombeRWahlM. Inhibition of the pial artery constriction induced by sympathetic stimulation by local microapplication of a cholinomimetic agent. J Cereb Blood Flow Metab1982;2:451–6.
30.
IbrahimMZM. The mast cells of the mammalian central nervous system. I. Morphology, distribution and histochemistry. J Neurol Sci1974;21:431–78.
31.
KarnushinaILPalaciosJMBarbinGJoóE DuxSchwartzJC. Studies on a capillary-rich fraction isolated from brain: histamine components and characterization of the histamine receptors linked to adenylate cyclase. J Neurochem1980;34:1201–8.
32.
GrossPMHarperAMTeasdaleGM. Interaction of histamine with noradrenergic mechanisms in cerebral arteries and veins. In: HeistadDDMarcusML eds Cerebral blood flow: effects of nerves and neurotransmitters. New York: Elsevier—North Holland, 1982;197–209.
33.
GrossPMHarperAMTeasdaleGM, Cerebral circulation and histamine: 1. Participation of vascular H1 and H2 receptors in vasodilatatory responses to carotid arterial infusion. J Cereb Blood Flow Metab1981;1:97–108.
34.
EdvinssonLKrauseDN. Pharmacological characterization of GABA receptors mediating vasodilation of cerebral arteries in vitro. Brain Res1979;173:89–97.
35.
KrauseDNWongEDegenerPRobertsE. GABA receptors in bovine cerebral blood vessels: binding studies with 3H-muscimol. Brain Res1980;185:51–7.
36.
McCullochJKellyPAT. Dopaminergic mechanisms and relationship between local cerebral glucose utilization and local blood flow. In: HeistadMMMarcusML eds Cerebral blood flow: effects of nerves and neurotransmitters. New York: Elsevier—North Holland1982:129–35.
37.
LamarJ-CEdvinssonL. 5-Hydroxytryptamine receptors contractile activity and mode of inhibition by methysergide in mammalian intracranial and extracranial vessels. Arch Int Pharmacodyn1980;243:245–54.
38.
Di CarloV. Histochemical evidence for a serotoninergic innervation of the microcirculation in the brainstem. In: OwmanChEdvinssonL eds Neurogenic control of the brain circulation. New York: Pergamon Press, 1977:55–8.
39.
ReinhardJFLiebmannJESchlosbergAJMoskowitzMA. Serotonin neurons project to small blood vessels in the brain. Science1979;206: 85–6.
40.
MessingRBLytleLD. Serotonin-containing neurons: their possible role in pain and analgesia. Pain1977;4:1–21.
41.
DuckiesSP. Vasoactive peptides and cerebral circulation. In: BevanJAFujiwaraMMaxwellRAMohriKShibataSTodaN eds Vascular neuroeffectors mechanisms: 4th International Symposium. New York: Raven Press, 1983:223–8.
42.
Liu-ChenL-YHanDHMoskowitzMA. Pia arachnoid contains substance P originating from trigeminal neurons. Neuroscience1983;9:803–8.
43.
ZawadzkiJVFurchgottRFCherryP. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by substance P. Fed Proc1981;40:689.
44.
MoskowitzMA. The neurobiology of vascular head pain. Ann Neurol1984;16:157–68.
45.
De MarinisMMartucciNGagliardiFMFelicianiMAgnoliA. Trigeminal control of cranio-facial vasomotor response. Cephalalgia1984;4:243–51.
46.
MoskowitzMAReinhardJFRomeroJ. Neurotransmitters and the fifth cranial nerve: is there a relation to the headache phase of migraine?. Lancet1979; 2:883–4.
47.
HankoJHHardeboJE. Enkephalin-induced dilatation of arteries in vitro probably mediated by opiate receptors. Europ J Pharmacol1978;51:295–7.
48.
PepperCMHendersonG. Opiate and opioid peptides hyperpolarize locus coeruleus neurons in vitro. Science1980;209:294–396.
49.
JesselTIversenLL. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature1977;268:549–51.
50.
PonteJPurvesMS. The role of the carotid body chemoreceptors and carotid sinus baroreceptors in the control of cerebral blood vessels. J Physiol1974;237:315–40.
51.
HansenJTChristieDS. Rat carotid body catecholamines determined by high-performance liquid chromatography with electrochemical detection. Life Sci1981;29:1791–5.
52.
LundbergJMHökfeltTFahrenkrugJNilssonGTereniusL. Peptides in the cat carotid body (glomus caroticum): VIP-, enkephalin-, and substance P-like immunoreactivity. Acta Physiol Scand1979;107:279–81.
53.
WilsonSPKleinRLChangK-JGasparisMSViverosOHYangW-H. Are opioid peptides co-transmitters in noradrenegic vesicles of sympathetic nerves?. Nature1980; 288:707–9.
54.
NakaiMIadecolaCRuggieroDATuckerLWReisDJ. Electrical stimulation of cerebellar fastigial nucleus increases cerebral cortical blood flow without change in local metabolism: evidence for an intrinsic system in brain for primary vasodilation. Brain Res1983;260:35–49.
55.
IadecolaCArbitENakaiMMraovitchSTuckerLReisDJ. Increased regional cerebral blood flow and metabolism elicited by stimulation of the dorsal medullary reticular formation in the rat: evidence for an intrinsic neural system in brain regulating cerebral metabolism. In: HeistadDDMarcusML eds Cerebral blood flow: effects of nerves and neurotransmitters. New York: Elsevier—North Holland, 1982:485–92.
56.
WhiteLE. Thalamocorticai synaptic relations: a review with emphasis on the projections of specific thalamic nuclei to the primary sensory areas of the neocortex. Brain Res1979;1:275–311.
57.
AntonyM. Biochemical indices of sympathetic activity in migraine. Cephalalgia1981;1:83–9.
58.
HiltonBPCumingsJN. 5-hydroxytryptamine ieveis and platelet aggregation responses in subjects with acute migraine headache. J Neurol Neurosurg Psychiatry1971;35:505–9.
59.
AnselmiBBaldiECasacciFSalmonS. Endogenous opioids in cerebrospinal fluid and blood in idiopathic headache sufferers. Headache1980;20:294–9.
60.
SicuteriF. Opioid receptor impairment—underlying mechanism in “pain diseases”?. Cephalalgia1981; 1:77–82.
61.
LauritzenMSkyhøj OlsenTPaulsonOB. Characteristics of the gradually spreading reduction of regional cerebral blood flow in classic migraine. Acta Neurol Scand [Suppl 90]1982;65:70–1.
62.
KatayamaYUenoYTsukiYamaTTsubokawaT. Long lasting suppression of firing of cortical neurons and decrease in cortical blood flow following train pulse stimulation of the locus coeruleus in the cat. Brain Res1981;216:173–9.
63.
BasbaumALFieldsHL. Endogenous pain control mechanisms: review and hypothesis. Ann Neurol1978;4:451–62.
64.
YakshTL. Direct evidence that spinal serotonin and noradrenaline terminals mediate the spinal antinociceptive effects of morphine in periaqueductal grey. Brain Res1979;160:180–5.
65.
Muller-SchweinitzerEFanchampsA. Effects on arterial receptors of Ergot derivatives used in migraine. Adv Neurol1982;33:343–56.
66.
MeyerJSHardenbergJ. Clinical effectiveness of calcium entry blockers in prophylactic treatment of migraine and cluster headaches. Headache1983;23:266–77.
67.
AgnoliADenaroACeciEFalaschiP. On the etiopathogenesis of migraine: a possible link between the amines and endorphin hypotheses. Adv Neurol1982;33:99–106.
