Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient is described with a 17-year history of intractable left-sided facial pain. The pain occurred daily in 5 sec spasms to a maximum of one every 2-3 min and was restricted to the left upper face. It was associated with rhinorrhoea on the left and often with ipsilateral facial flushing. Conventional therapy, including carbamazepine, baclofen and three posterior fossa explorations, had not provided lasting relief. Local facial stimulation by tapping a painful trigger point led to both pain and flushing of the face ipsilaterally. During this flushing, blood was collected and assayed using sensitive radioimmunoassays for several neuropeptides (neuropeptide Y, substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide). A marked (119%) increase in calcitonin gene-related peptide was noted in the external jugular vein blood ipsilaterally during the flushing with no change in the other peptides measured. To quantitate the effect of calcitonin gene-related peptide on human extracranial vessels, standard pharmacological procedures were used to examine the potency of the peptide as a vasodilator of human facial artery. The IC50 of calcitonin gene-related peptide for the prostaglandin F2 alpha-precontracted human facial artery was 10(-9) mol/l. The relevance of these observations to the clinical problem of migraine is considered.
Cephalalgia 1992 Feb
PMID:Cutaneous sensory stimulation leading to facial flushing and release of calcitonin gene-related peptide. 155 59

The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine.
 ...
PMID:Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. 169 72

The cerebral vascular neuromuscular apparatus consists of a varicose perivascular nerve plexus at the adventitial-medial border and smooth muscle cells in the medial coat that are functionally connected. In addition to noradrenaline and acetylcholine, a number of putative non-adrenergic, non-cholinergic neurotransmitters have been identified in cerebral perivascular nerves, including serotonin, substance P, vasoactive intestinal polypeptide, gastrin-releasing peptide, cholecystokinin, somatostatin, neurotensin, calcitonin gene-related peptide and neuropeptide Y. The role of adenosine-5'-triphosphate as a cotransmitter with noradrenaline in some perivascular sympathetic nerves, and of endothelial cells in mediating the vasodilatation produced by some neurohumoral agents is discussed. Speculations are made about the relation between vascular neuroeffector mechanisms and migraine, including the possibility of local vasospasm by serotoninergic nerves, reactive hyperaemia involving purine nucleotides and nucleosides, release of substance P from sensory nerve collaterals during antidromic ('axon reflex') impulses and secondary release of local agents such as prostanoids, histamine and bradykinin.
Cephalalgia 1985 May
PMID:Neurogenic control of cerebral circulation. 241 Jan 33

It has been suggested that a number of peptides may be involved in the transmission of pain. In order to evaluate the possible role of peptides in the development of headache, we have, in the present study, examined the presence of nerve fibres containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in human temporal and occipital tissues. In the skin, delicate VIP, SP and CGRP fibres occur beneath the epidermis, sometimes running into the folds of the dermal ridges. In deeper layers of the dermis, small blood vessels are occasionally surrounded by single nerve fibres containing NPY, VIP, SP and CGRP. Large temporal and occipital arteries are surrounded by a meshwork of such fibres. In addition, NPY and VIP fibres are seen around sweat glands and hair follicles. Smooth muscle bundles in the dermis are surrounded by VIP fibres, whereas the temporal muscle per se is devoid of such fibres.
 ...
PMID:Peptide-containing nerve fibres in human extracranial tissue: a morphological basis for neuropeptide involvement in extracranial pain? 243 70

In eight patients carotid angiography was required for evaluation of transient neurological attacks. Cerebral blood flow results, angiography and clinical observations subsequently suggested the diagnosis of migraine. We measured plasma concentrations of substance P(SP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in repeated blood samples obtained from the carotid artery and the internal jugular vein in conjunction with cerebral angiography followed by 4 to 6 repeated recordings of regional cerebral blood flow (rCBF) with the intracarotid Xenon-133 injection technique. This technique is known to induce attacks of migraine with aura in many sufferers. Four patients developed aura symptoms. In three this was succeeded by throbbing headache. Typical, migraine-related, focal hypoperfusion occurred in conjunction with the aura symptoms. The remaining four patients had no symptoms or rCBF changes. There were no systematic or statistically significant changes over time in arterial-venous plasma concentrations or in the release rates of any of the peptides. All migraineurs had an overall elevated mean CGRP value compared to control values from the literature. The overall plasma levels of the potent vasoconstrictor NPY were higher (p < 0.10) in the group that developed symptoms and rCBF changes (136 pmol/l) than in the non-symptomatic group (97 pmol/l). The difference in NPY levels could perhaps be associated with the focal rCBF decrease seen in the attack group.
Cephalalgia 1994 Feb
PMID:Absence of vasoactive peptide release from brain to cerebral circulation during onset of migraine with aura. 751 29

Cluster headache is a rare very severe disorder that is clinically well characterized with a relatively poorly understood pathophysiology. In this study patients with episodic cluster headache fulfilling the criteria of the International Headache Society were examined during an acute spontaneous attack of headache to determine the local cranial release of neuropeptides. Blood was sampled from the external jugular vein ipsilateral to the pain before and after treatment of the attack. Samples were assayed for calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P and neuropeptide Y. Attacks were treated with either oxygen inhalation, sumatriptan or an opiate. Thirteen patients were studied of whom 10 were male and three female. All had well-established typical attacks of cluster headache when blood was sampled. During the attacks external jugular vein blood levels of CGRP and VIP were raised while there was no change in neuropeptide Y or substance P. Calcitonin gene-related peptide levels rose to 110 +/- 7 pmol/l (normal: < 40) while VIP levels rose to 20 +/- 3 pmol/l (normal: < 7). Treatment with both oxygen and subcutaneous sumatriptan reduced the CGRP level to normal, while opiate administration did not alter the peptide levels. These data demonstrate for the first time in vivo human evidence for activation of the trigeminovascular system and the cranial parasympathetic nervous system in an acute attack of cluster headache. Furthermore, it is shown that both oxygen and sumatriptan abort the attacks and terminate activity in the trigeminovascular system.
 ...
PMID:Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. 751 21

A rich supply of nerve fibers containing neuropeptide Y-like (NPY-LI) and tyrosine hydroxylase-like immunoreactivity was seen in human cerebral arteries, arterioles and veins. Only a sparse supply of vasoactive intestinal polypeptide (VIP-LI), substance P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was demonstrated in the walls of human cerebral vessels. In isolated ring segments of human cerebral arteries, NPY and noradrenaline caused vasoconstriction but did not potentiate each other. VIP, peptide histidine methionine, SP, neurokinin A, and CGRP relaxed arteries precontracted by prostaglandin F2 alpha. The degree of innervation and the vasomotor responses are discussed in relation to migraine pathophysiology.
Cephalalgia 1994 Apr
PMID:Demonstration of neuropeptide containing nerves and vasomotor responses to perivascular peptides in human cerebral arteries. 752 Mar 66

The article briefly describe the innervation of the human cerebral circulation by nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). The neuropeptides in human cerebral arteries were characterized by radioimmunoassay in combination with HPLC. These neuropeptides mediate contraction (NPY) and dilation (VIP, SP, CGRP). In conjunction with spontaneous attacks of migraine or cluster headache, release of CGRP is seen. With the associated symptoms of nasal congestion and rhinorrhea, VIP is released. Successful treatment may abort the peptide release in parallel with disappearance of headache.
Cephalalgia 1995
PMID:Neuropeptides in the cerebral circulation: relevance to headache. 758 22

The cerebral circulation is invested by a rich network of neuropeptide Y (NPY) and noradrenaline containing sympathetic nerve fibers in arteries, arterioles and veins. However, the nerve supply of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) containing fibers is sparse. While noradrenaline and NPY cause vasoconstriction, VIP, SP and CGRP are potent vasodilators. Stimulation of the trigeminal ganglion in cat and man elicits release of SP and CGRP. Subjects with spontaneous attacks of migraine show release of CGRP in parallel with headache. Cluster headache patients have release of CGRP and VIP during bouts. Treatment with sumatriptan aborts headache in migraine and cluster headache as well as the concomitant peptide release.
Cephalalgia 1994 Oct
PMID:Neuropeptides in migraine and cluster headache. 782 88

The functional role of the trigeminal system has been addressed in experiments on the cortical surface of alpha-chloralose anaesthetized cats. Application of calcitonin gene-related peptide (CGRP) caused a concentration-dependent increase in arteriolar calibre by 38 +/- 5% (n = 8) with an IC50 of 2 nM. Cerebral veins did not relax upon CGRP administration (n = 12). Substance P (SP) was less potent but showed dilatation of both arterioles (21 +/- 4%) and veins (16 +/- 4%). The cerebrovascular trigeminal system was investigated after chronic (14 days) surgical lesion of the trigeminal nerve with the concomitant disappearance of perivascular CGRP/SP immunoreactive nerves. The cortical arteriolar responses to subarachnoid microinjections of acidic (pH 6.8) and basic CSF (pH 7.6) as well as noradrenaline (10(-4) M), neuropeptide Y (10(-7) M), prostaglandin F2x (10(-6 M), barium chloride (10(-4) M), and autologous blood (5 microl) were examined in anaesthetized cats with lesions of the trigeminal nerve, and were compared with their effects in sham-operated animals. The magnitude of the vasodilator and vasoconstrictor responses to these agents was unaffected by trigeminal lesions. However, duration of the vasoconstriction produced by basic CSF, but not the vasodilitation to acidic CSF, was markedly prolonged by trigeminal lesions (from 0.8 +/- 0.1 min to 2.2 +/- 0.3 min, p < 0.01). Also, the vasoconstrictor responses to noradrenaline, prostaglandin F2x, barium chloride, and autologous blood were significantly prolonged, while the maximum contractile effect to each agent was similar in lesioned as in sham-operated controls. The effects of CGRP, SP, and neurokinin A (NKA) have been examined on isolated cerebral arteries in vitro. Different CGRP analogues induced a strong relaxation with no difference in Imax (85-96%) or pD2 values (8.65 - 9.12). NKA induced a stronger relaxation than SP (Imax: 33% and 13%, respectively). SP was more potent than NKA (pD2:8.7 and 7.7, respectively). Capsaicin, a substance which selectively causes the release of stored sensory neuropeptides (CGRP, SP, NKA), caused in vitro relaxation of precontracted arteries. This relaxation was not affected by the neurokinin blocker spantide, but shifted towards higher capsaicin concentrations by the CGRP antagonist (CGRP 8-37. Thus, in this preparation CGRP rather than a neurokinin (SP/NKA) is responsible for the capsaicin-induced dilatations.
Cephalalgia 1995 Oct
PMID:Modification of vasoconstrictor responses in cerebral blood vessels by lesioning of the trigeminal nerve: possible involvement of CGRP. 853 89


1 2 3 Next >>