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

The absolute indomethacin effect in some unilateral headaches may, at least partially, be cyclooxygenase inhibition-independent. Aspirin and indomethacin, for example, may inhibit the neurogenically induced plasma extravasation in rat dura mater. Given the putative involvement of trigeminal neuropeptides in the pathophysiology of these conditions, the influence of cyclooxygenase inhibitors (indomethacin, acetylsalicylic acid (ASA) and naproxen) has been studied upon substance P, calcitonin gene-related peptide and vasoactive intestinal peptide (VIP)-induced vasodilatation in PGF2 alpha precontracted porcine ophthalmic arteries in vitro. None of the cyclooxygenase inhibitors significantly altered the effects of calcitonin gene-related peptide. The 10(-10) mol/l VIP-induced relaxation was inhibited significantly by all three cyclooxygenase inhibitors. Substance P-induced relaxation (from 10(-10) to 10(-8) mol/l) was enhanced by ASA and inhibited both by naproxen and, to a lesser extent, by indomethacin. The results suggest mainly that VIP-induced relaxations, particularly at lower concentrations, may be inhibited by all three cyclooxygenase inhibitors, and that naproxen, to a greater extent than aspirin or indomethacin, showed a tendency to inhibit vasodilatation induced by all peptides.
Cephalalgia 1992 Feb
PMID:Cyclooxygenase inhibitors modify the relaxant effect of vasoactive intestinal polypeptide and substance P in isolated porcine ophthalmic artery. 137 9

Neurogenic inflammation has been proposed as a possible pathogenetic mechanism for migraine and cluster headache. Antidromic stimulation of trigeminal fibers causes plasma protein extravasation, mast cell activation and degranulation, vacuolation and increase in endothelial vesicle number within post capillary venules in rat dura mater. The antimigraine drugs sumatriptan and dihydroergotamine block the development of plasma extravasation and ultrastructural changes, as well as plasma calcitonin gene-related peptide (CGRP) increase in the superior sagittal sinus following electrical trigeminal ganglion stimulation. Sumatriptan and dihydroergotamine bind with high affinity to the 5-HT1D/1B receptors, thus suggesting that their neurogenic antiinflammatory activity is mediated by activation of 5-HT autoreceptors present on sensory fibers innervating blood vessels in dura mater.
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PMID:The trigemino-vascular system and migraine. 137 7

Lithium is currently a major drug used as a treatment for affective disorders and cluster headache, among other conditions. Its mechanism of action remains unknown. The trigeminovascular system may be involved in the pathophysiology of cluster headache and related diseases by liberating neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) in the eye-forehead region. The objective of this study was to investigate whether or not a low concentration of lithium may interfere with peptidergic neuro-transmission at this level. Vasoactive intestinal peptide (VIP), SP, CGRP, capsaicin, and SP+CGRP concentration-response relaxation curves were obtained in the presence and absence of 2 x 10(-4) M lithium in isolated porcine ophthalmic arteries. Lithium inhibited the SP and VIP, but not the CGRP responses. Capsaicin-(a neurotoxin causing release of stored sensory neuropeptides) induced relaxations were partially inhibited by lithium. It is concluded that lithium may interfere with SP- and VIP-induced relaxation. If SP and VIP are of pathogenic significance in cluster headache, lithium may possibly work by counteracting unwanted effects of such peptides.
Headache 1992 Jul
PMID:Lithium inhibits substance P and vasoactive intestinal peptide-induced relaxations on isolated porcine ophthalmic artery. 138 46

Although it is known that pain in the forehead may be induced by neck abnormalities, the actual neck-head connections responsible for development of pain in trigeminal areas are poorly understood. Vasoactive neuropeptides released from sensory fibres, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been considered as important elements in headache pathophysiology. The levels of CGRP-like immunoreactivity (LI) were measured bilaterally in the jugular blood (52 rats) and intraocular aspirates (66 rats) following electrical stimulation of the left greater occipital nerve, and in the jugular blood of 13 control animals. One-third of the stimulated rats had varying combinations of conjunctival injection, tearing, diminished eye aperture and miosis or mydriasis on the stimulated side. The other two-thirds exhibited no ocular signs. Significantly lower levels of CGRP-LI were present in the jugular blood on the stimulated side in comparison with control rats. There was comparatively lower CGRP-LI on the non-stimulated side as well, but to a lesser extent. Significant differences between the stimulated and the non-stimulated side were present, particularly in the tearing/diminished eye cleft group. It is proposed that stimulation of the rat GON inhibits the trigeminal system (reduction of CGRP-LI) and possibly activates parasympathetic fibres (ocular changes).
Cephalalgia 1992 Oct
PMID:Reduction of calcitonin gene-related peptide in jugular blood following electrical stimulation of rat greater occipital nerve. 142 57

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 cerebral vasodilator response induced by topical nitroglycerin and nitroprusside was examined in cats equipped with cranial windows for the observation of the cerebral microcirculation. In cats subjected to chronic unilateral trigeminal ganglionectomy, the vasodilator responses to nitroprusside and nitroglycerin were markedly depressed on the denervated side. Application of a selective calcitonin gene-related peptide (CGRP) antagonist [CGRP(8-37)] on the innervated side reduced the response to nitrodilators to the same extent as seen on the denervated side. The vasodilator response to acetylcholine was unaffected by trigeminal ganglionectomy. CGRP(8-37) almost abolished the vasodilator response to nitroglycerin and sodium nitroprusside and to CGRP, but did not affect the response to adenosine or to adenosine diphosphate. Pretreatment with LY83583, a drug that lowers cyclic GMP levels, diminished the vasodilation to CGRP and to nitroprusside but not to adenosine. We conclude that the nitrovasodilators activate sensory fibers to release CGRP, which in turn relaxes cerebral vascular smooth muscle by activating guanylate cyclase. Hence, nitrovasodilators possess a novel mechanism of action within the cephalic circulation which may explain both the occurrence of vasodilation and headache.
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PMID:Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. 157 43

Neurogenic plasma extravasation, endothelial cell activation (increase in vesicle number and vacuole formation), platelet aggregation and adhesion, and mast cell degranulation occur selectively in post-capillary venules of the dura mater following electrical trigeminal ganglion stimulation, and are mediated by release of neuropeptides from perivascular unmyelinated C fibres. Pre-treatment with the antimigraine drugs dihydroergotamine and sumatriptan, two drugs that bind with high affinity to 5-HT1B/1D receptors, markedly attenuated plasma protein extravasation induced by electrical trigeminal ganglion stimulation. Trigeminal stimulation increased plasma calcitonin gene-related peptide levels in rat superior sagittal sinus. Pre-treatment with dihydroergotamine and, to a lesser extent, sumatriptan, attenuated this increase. Both drugs reduced morphological changes in post-capillary venules and mast cells within dura mater following electrical trigeminal ganglion stimulation. Plasma protein extravasation was selectively blocked in dura mater (but not in extracranial tissues) by pre-treatment with those receptor agonists showing a rank order of potency suggesting a 3-HT1B/1D interaction (5-CT greater than 5-BT greater than DHE greater than sumatriptan greater than 8-OH-DPAT). Pre-treatment with 5-HT2 and 5-HT3 antagonists was not effective. Taken together, these data are consistent with the interpretation that putative 5-HT-1B/1D receptors located on sensory fibres are coupled to inhibition of peptide release and blockade of neurogenic inflammation. An important therapeutic action of ergot alkaloids and sumatriptan in migraine headaches is so defined.
Cephalalgia 1991 Sep
PMID:Evidence for 5-HT1B/1D receptors mediating the antimigraine effect of sumatriptan and dihydroergotamine. 166 Mar 51

The spinal accessory nerve has been generally thought to be a cranial nerve with purely motor function, innervating the trapezius and sternocleidomastoid muscles. The present study identified clusters of sensory neurons consistently associated with this cranial nerve in adult rats. Either a single microganglion or several dispersed microganglia were found that adhered to the spinal root of the nerve, to small vessels, or were free within the subarachnoid space. The neurons of the ganglion had axons that joined the spinal root of the nerve proximal to its exit from the skull. Additional branches appeared to have an intracranial distribution within the arachnoid of the brainstem and along its vessels. Several findings suggest that the function of the ganglion is sensory and not autonomic. First, the architectural features of neurons within the ganglion (including their size, pseudounipolar morphology, and the lack of synaptic contacts) are similar to those of neurons in other sensory ganglia. Second, substance P and calcitonin gene-related peptide coexist within neurons of the microganglion, whereas markers for the major transmitters found in autonomic ganglia in rats are absent. Third, the expression of peptides in neurons of the ganglion was sensitive to neonatal capsaicin treatment. Finally, neurons within the ganglion were filled with a retrogradely transported dye after injection of the dye into the cervical spinal cord. Although the function of the ganglion is not known, its features are consistent with a role in nociception from the muscles of the spinal accessory complex, and it may be involved in headaches that have an occipital distribution.
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PMID:Detection and characterization of a sensory microganglion associated with the spinal accessory nerve: a scanning laser confocal microscopic study of the neurons and their processes. 167 15

Substance P, calcitonin gene-related peptide and vasoactive intestinal polypeptide-like immunoreactivities have been evaluated in the saliva of 15 subjects suffering from migraine without aura and 16 control subjects. All three peptides were also measured in the symptomatic/non-symptomatic side saliva sampled from 10 cluster headache sufferers during the cluster period, 5 cluster headache sufferers out of the cluster period, as well as in the right and left side saliva of 18 control subjects. The most interesting result gives a clear difference in common migraine and cluster headache salivary vasoactive intestinal polypeptide-like immunoreactivity contents. In fact, these are enhanced during cluster headache attack and decreased during migraine attack when compared with the interictal period vasoactive intestinal polypeptide-like immunoreactivity levels. Another remarkable finding concerns the significant increase of substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity levels, from basal values, in the saliva sampled during both migraine and cluster headache attacks. Control subjects showed a calcitonin gene-related peptide-like immunoreactivity and substance P-like immunoreactivity salivary contents significantly higher than migraine sufferers' saliva sampled in basal conditions. Conversely, calcitonin gene-related peptide-like immunoreactivities levels in controls were lower than in cluster headache sufferers' saliva obtained during intervals. Finally, during cluster headache attacks the enhancement of substance P-like immunoreactivity and vasoactive intestinal polypeptide-like immunoreactivity salivary contents interest the non-symptomatic side, whereas the symptomatic side salivary substance P-like immunoreactivity and vasoactive intestinal polypeptide-like immunoreactivity contents remain unchanged. These findings do not allow any final conclusion. However, this biochemical evaluation indicates relevant changes of the salivary neuropeptides in diseases, such as migraine and cluster headache, in which pain transmission is surely involved.
Cephalalgia 1990 Feb
PMID:Sensory neuropeptides (substance P, calcitonin gene-related peptide) and vasoactive intestinal polypeptide in human saliva: their pattern in migraine and cluster headache. 169 Jun 1

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.
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PMID:Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. 169 72


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