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 headache phase of migraine may develop as the result of an abnormal interaction (and perhaps an abnormal release) of vasoactive neurotransmitters from terminals of the trigeminal nerve with large intracranial and extracranial blood-vessels. These blood-vessels, which dilate during the headache phase of migraine, are thought to receive axonal projections from all three divisions of the trigeminal nerve. Substance P, a potent vasodilating peptide, seems to be released from trigeminal nerve endings in response to nervous stimulation and is involved in the transmission of painful stimuli within the periphery. The vasoactive molecule serotonin, implicated in the pathogenesis of migraine, coexists with substance P in some terminals of the central nervous system and is present within the trigeminal ganglia. Within this nerve serotonin may modulate the function of primary sensory neurons. The abnormal release of substance P or as yet unidentified peptides or other transmitters from the fifth cranial nerve may explain both the hemicranial pain and the vasodilation which are characteristic of the headache of migraine.
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PMID:Neurotransmitters and the fifth cranial nerve: is there a relation to the headache phase of migraine? 9 Sep 71

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

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

Substance P (SP), present in sensory afferent neurons, seems to process nociceptive information in the trigeminal system. SP, released from peripheral trigeminal endings, causes typical cluster headache (CH) signs, e.g. vasodilatation, conjunctival and nasal edema and miosis. Opiates and somatostatin (SRIF), both active in relieving CH attack, inhibit SP release from the central and peripheral trigeminal system. In the present study, plasma and cerebrospinal fluid (CSF), SP-like immunoreactivity (SPLI) and enkephalinase activity (EKA), and plasma SRIF-like immunoreactivity (SRIFLI) have been evaluated during spontaneous and histamine induced attacks in the cluster phase. During the histamine provoked attacks, CSF SPLI and plasma SRIFLI and EKA were unchanged, while plasma SPLI decreased significantly. During spontaneously occurring attacks, plasma SRIFLI was found to be unmodified and a significant lowering of SPLI was detected when compared with controls. Moreover, both during and between attacks in the cluster phase, plasma EKA was increased in comparison with the values in controls. It remains to be seen whether variations of plasma SPLI and EKA levels play a role in the CH mechanism.
Cephalalgia 1985 Sep
PMID:Substance P mechanism in cluster headache: evaluation in plasma and cerebrospinal fluid. 241 4

Substance P, present in primary sensory neurones, seems to take part in nociceptive transmission within the trigeminal system. Substance P, released by peripheral axons of these neurones, induces vasodilatation, plasma extravasation, miosis, conjunctival and nasal congestion. All these effects bear some similarity to symptoms of cluster headache and migraine attack. Opiates and somatostatin inhibit the release of substance P from primary sensory neurones and relieve both pain and autonomic symptoms of cluster headache attack. Plasma substance P-like immunoreactivity was decreased during spontaneous attack of cluster headache and migraine and during histamine precipitated attack of cluster headache. Taken together these data suggest that substance P and endogenous opioids could be implicated in the pathophysiology of cluster headache and migraine.
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PMID:Substance P and enkephalins: a creditable tandem in the pathophysiology of cluster headache and migraine. 243 12

Substance P-like immunoreactivity (SP-LI) was measured by radioimmunoassay in iris, choroid, and retina obtained from men after death. Although present in different amounts, SP-LI, eluting as authentic SP or SP sulfoxide in the high-performance liquid chromatography system, was found in the three ocular structures. The retina contained higher concentrations of SP-LI than the iris and choroid. The possible functional involvement of iris SP was studied in 22 episodic cluster headache (CH) patients by using the anticholinesterase agent echothiophate iodide (EI), which also induces an atropine-resistant miosis, putatively due to release of SP from trigeminal sensory neurons. In CH patients EI eye drops instilled into both eyes provoked a prolonged miosis with a more marked response in the pupil of the symptomatic eye. It is proposed that the hyperfunction of SP-containing neurons may coexist with the previously documented sympathetic hypofunction in the innervation of the symptomatic pupil of CH.
Cephalalgia 1988 Mar
PMID:Substance P in the human iris: possible involvement in echothiophate-induced miosis in cluster headache. 245 18

Headaches can be of sinugenic origin even if this cause may not be suspected from the case history. Endoscopy of the lateral nasal wall with rigid cold light endoscopes in combination with polytomography or computed tomography usually will reveal the underlying causes hidden from the unaided eye, the operating microscope, and standard x-ray examination. Small lesions in the lesser cells of the ethmoid complex may give rise to headaches, especially when located in the key areas of the ethmoid infundibulum or frontal recess. Many anatomic variations of the structures in the middle meatus can narrow the stenotic clefts even more and thus predispose to more or less intense contact of opposing mucosal surfaces. This may impede or block ventilation and drainage of the ethmoid and surrounding larger sinuses and thus affect those as well. After identification of these underlying causes, functional endoscopic sinus surgery with usually minimal operations often can provide dramatic relief of symptoms that may have been present for months or even years. The neuropeptides recently were newly identified as a group of mediators besides the neurotransmitters noradrenalin and acetylcholine. Substance P (SP) is one of the most important neuropeptides that we can identify in the human nasal mucosa. It mediates pain impulses to the cortex via afferent C fibers. Simultaneously from polymodal receptors in the nasal mucosa, local reflexes are mediated by SP via an axon reflex, causing vasodilatation, plasma extravasation ("neurogenic edema"), and hypersecretion. The receptors can be stimulated by chemical and caloric irritants and also mechanical irritants such as pressure. The pressure exerted on nasal mucosa by polyps or mucosal swelling due to other reasons in the ethmoid clefts, cells, and narrow spaces apparently can be enough to trigger an SP-mediated pain sensation via afferent C fibers. Over the axon reflex an initially small lesion may lead in a vicious circle to quite significant symptoms. The model of "referred pain" explains why the pain is not necessarily felt at its origin, but may be projected onto corresponding dermatomes. The pain-mediating function of SP can be blocked selectively by capsaicin, the pungent component of red pepper, which leads to desensitization of the receptors and degeneration of the afferent C fibers without affecting other sensory qualities. In patients with vasomotor rhinitis we were able to block all the patients' symptoms including headaches by topical administration of capsaicin. After identification of underlying causes with endoscopy and CT, lesions and contact areas should be operated upon if medical treatment fails.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Headaches and sinus disease: the endoscopic approach. 314 Jul 3

In order to clarify the mechanism of the analgesic effect of ceruletide (CRL), the peptides B-endorphin (BE), ACTH, prolactin (PRL), growth hormone (GH) and substance P were determined in the basal state and following IV CRL administration in 11 patients. CRL, at the dose of 2 ng/kg/min, significantly augmented BE levels in the plasma, and in CSF. Substance P levels were significantly augmented by CRL in the plasma, while ACTH levels were significantly augmented in CSF. GH and PRL levels were not affected by CRL. Placebo had no effect on any of the measured peptides. The effect of CRL on mood and anxiety, known to be affected by opioids, was studied in 14 patients with psychogenic headache. The effect of histamine induced headache on State trait anxiety inventory and on Mood adjective check list was studied before and after administration of placebo or CRL. CRL significantly diminished anxiety when compared to placebo. Elation, surgency and egotism were significantly augmented while skepticism was significantly diminished by CRL. The CRL effect on mood and pain may be mediated by augmented levels of neurohormones both in the plasma and in CSF.
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PMID:Effect of ceruletide on pituitary-hypothalamic peptides and on emotion in man. 617 96

Substance P appears to be involved in the transmission of pain signals from the periphery to the spinal cord and brain stem. Substance P containing neurons are responsible for the neurogenic vasodilation identical to that obtained by substance P release evoked by antidromic stimulation of these fibres. Both endogenous opioids and somatostatin inhibit the release of substance P from central and peripheral endings. Present pharmacological investigations conclude that morphine and somatostatin are as effective as ergotamine in reducing the pain of CH. All three drugs are significantly more active than placebo. Somatostatin and opiates could act by inhibiting the release of substance P.
Cephalalgia 1983 Aug
PMID:Substance P and endogenous opioids: how and where they could play a role in cluster headache. 619 86

Nervous connections between the trigeminal ganglia and cerebral blood vessels have recently been identified in experimental animals and have been termed the trigeminovascular system. Existence of this system in humans is inferential. Trigeminovascular neurons and their peripheral unmyelinated nerve fibers contain the neurotransmitter peptide substance P. Most newly synthesized substance P is transported from ganglion cell bodies to afferent nerve fibers, where depolarization-induced release of neurotransmitter into the wall of the cerebral blood vessel occurs. Substance P dilates pial arteries, increases vascular permeability, and activates cells that participate in the inflammatory response. The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.
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PMID:The neurobiology of vascular head pain. 620 79


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