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)

Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1-TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea.
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PMID:Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries. 1502 32

There now is one realized and several attractive targets for the treatment of acute attacks of migraine that will follow and augment the use of serotonin 5-HT1B/1D receptor agonists, the triptans. Calcitonin gene-related peptide (CGRP) receptor blockade recently has been shown to be an effective acute antimigraine strategy; therefore, blockade of CGRP release by inhibition of trigeminal nerves would seem a logical approach. A number of targets are reviewed in this article including serotonin 5-HT1F and 5-HT1D receptors, adenosine A1 receptors, nociceptin, vanilloid TRPV1 receptors, and anandamide CB1 receptors. Development of one or more such compound offers the exciting prospect of new non-vasoconstrictor treatments for migraine and cluster headache.
Curr Pain Headache Rep 2004 Oct
PMID:Post-triptan era for the treatment of acute migraine. 1536 24

Transient receptor potential (TRP) channels are involved in a wide range of processes ranging from osmoregulation, thermal, chemical and sensory signalling, and potentially in the pathophysiology associated with several diseases. Patents for TRPV1 antagonists alone span diseases ranging across chronic pain, neuropathies, headache, bladder disorders, irritable bowel syndrome (IBS), gastro-oesophageal reflux disease (GORD), and cough amongst others. Most research is currently focused around those TRP channels involved in sensory processes, with the neurogastroenterology and motility field playing a major role, for example, through recent discoveries of differential roles for TRPV receptor subtypes in chemosensitivity and mechanosensitivity of visceral afferents. At this time, however, the understanding of the role of even TRPV1, let alone most of the other TRP channels in disease pathophysiology is only just beginning, and although enthusiasm around the therapeutic potential for modulators of these channels is understandable, based largely upon the experience of the effects of natural ligands, such as capsaicin, the sheer size and complexity of the TRP family as a whole must serve as a warning against expecting too much too soon from drug discovery efforts.
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PMID:TRP channels as therapeutic targets: hot property, or time to cool down? 1691 27

The endogenous cannabinoid R(+)-methanandamide (mAEA) exerts differential anti- and pronociceptive effects by activating both cannabinoid (CB1) and vanilloid (TRPV1) receptors of nociceptive primary afferents. The significance of these effects in meningeal nociception was evaluated by modulation of calcitonin gene-related peptide (CGRP) release from meningeal afferents measured in an in vitro preparation of the hemisected rat skull. Temperature steps to 39 degrees C and 45 degrees C caused heat-dependent increases in CGRP release. One micromolar mAEA inhibited CGRP release at 32 degrees C but facilitated it at 45 degrees C. This effect was abolished in the presence of the TRPV1 receptor antagonist capsazepine. Lower doses of mAEA had no effect on basal or heat-evoked release. In the presence of the CB1 receptor antagonist SR141716 (0.2 microm) heat-stimulated increase in CGRP release was facilitated. CGRP release in the presence of SR141716 (0.2 microm) was further increased by adding mAEA at a concentration which had no effect on its own. These results confirm an opposing functional role for anandamide at CB1 and TRPV1 receptors on meningeal afferents.
Cephalalgia 2007 May
PMID:Cannabinoid and vanilloid effects of R(+)-methanandamide in the hemisected meningeal preparation. 1744 80

Migraine is a disorder that involves throbbing head pain with increased sensory sensitivity to light, sound, and head movement. Although the pathophysiology of migraine is still obscure, the excitement of the trigeminovascular system followed by the neurogenic inflammation in the dura mater has been implicated in the development of headaches. In addition, the TRPV1 receptor, which is known as one of the nociceptive receptors has recently been shown to express in the dura mater. These findings indicate an association between the TRPV1 receptor and migraine headaches. Furthermore, it suggests of a possibility that the TRPV1 receptor can act as a new therapeutic target for migraine. First, we reviewed the pathophysiology of migraine and the function of the TRPV1 receptor at first. Next, we introduce the possible therapeutic approaches for the application of this receptor for treating migraine; these approaches include regulation of neurotransmitter release via the TRPV1 receptor, regulation of pain conduction pathways via the TRPV1 receptor, and the regulation of the expression of the TRPV1 receptor.
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PMID:[TRPV1 receptor as a therapeutical target for the treatment of migraine]. 1969 84

Migraine is a largely inherited disorder of the brain characterized by a complex, but stereotypical, dysfunction of sensory processing. Often the most obvious clinical symptom is head pain, but non-headache symptoms such as photophobia, phonophobia and nausea are clearly part of the typical presentation. This review discusses the current pathophysiological concepts of migraine and migraine aura, such as a possible brainstem dysfunction and cortical spreading depression. Acute and preventive migraine treatment approaches are briefly covered with a focus on shortcomings of the currently available treatment options. A number of different receptors, such as calcitonin gene-related peptide (CGRP), TRPV1 and glutamate receptors, are currently being targeted by potential novel migraine therapeutics. The prospects of this research are exciting and are likely to improve patient care.
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PMID:Migraine pathogenesis and state of pharmacological treatment options. 1991 94

Migraine is among the most prevalent headache disorders and results from dysfunctions within the trigeminovascular system (TVS). The inflammatory processes that have been suggested to occur in the cascade of events resulting in migraine sensitise trigeminal nociceptors, possibly causing hyperalgesia and allodynia. Trigeminal nociceptors express the heat- and capsaicin-gated channel TRPV1, which seems to play a significant role in the development of peripheral and central sensitisation and of hyperalgesia and allodynia. Here, we review the molecular mechanisms leading to the sensitisation of TRPV1 and attempt to link them to migraine-relevant pathophysiological processes. We argue that antagonising TRPV1 sensitisation is a promising approach and should receive more attention in future research as well as in the development of anti-migraine drugs.
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PMID:TRPV1 in migraine pathophysiology. 2034 91

Migraine and anxiety disorders are frequently co-morbid with balance disorders. This study examined the relative distribution of subtypes of serotonin (5-HT) receptor in the inner ear of monkeys and rats. Most vestibular ganglion cells were immunoreactive for 5-HT(1B) and 5-HT(1D) receptors in macaques and rats. In the inner ear, 5-HT(1B) and 5-HT(1D) receptor immunopositivity was associated with endothelial cells of the vestibular ganglion, spiral ganglion, vestibulocochlear nerve, spiral ligament and stria vascularis. It was noteworthy that 5-HT(1B) and 5-HT(1D) receptors are expressed in parallel sites in peripheral vestibular and trigeminal systems, which may be a factor underlying the efficacy of triptans in treating migraine and migrainous vertigo. Because the vestibular ganglion and trigeminal ganglion are both within the subarachnoid space, an interaction between 5-HT(1B) and TRPV1 receptors on blood vessel and ganglion cells may also contribute to the vasospasm and the comorbid headache, dizziness, nausea and vomiting that accompany subarachnoid hemorrhage.
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PMID:Distribution of 5-HT1B and 5-HT1D receptors in the inner ear. 2051 Aug 90

Headache disorders are common and heterogenous neurologic entities. The complexities of management are further encumbered by the relatively few effective choices for acute and preventive therapies available to the headache specialist to treat these diverse disorders. As advances have been made in uncovering headache pathophysiology, new therapies have surfaced and others are forthcoming. This article will highlight new lines of care in development. There are several novel delivery mechanisms of familiar medications which bypass the limitations of current delivery systems, including the sumatriptan iontophoretic patch Zecuity, the intranasal sumatriptan OptiNose system, the zolmitriptan Rapidfilm orally dissolvable film and the orally inhaled dihydroergotamine Levadex system. New lines of care based upon recently discovered therapeutic targets will also be discussed including calcitonin gene-related peptide (CGRP) receptor antagonists, serotonin receptor agonists, and sphenopalatine ganglion (SPG) intermittent stimulation. Finally, emerging targets for future therapeutics will be explored including transient receptor potential vanilloid (TRPV1) receptor modulators, nitric oxide (NO) antagonists, gap junction modulators, glutamate receptor antagonists, orexin receptor antagonists and prostanoid receptor antagonists. Therapies developing over the next several years will be welcome additions to the headache specialist's armamentarium.
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PMID:Update on future headache treatments. 2369 55

Genetic studies have clearly shown that primary headaches (migraine, tension-type headache and cluster headache) are multifactorial disorders characterized by a complex interaction between different genes and environmental factors. Genetic association studies have highlighted a potential role in the etiopathogenesis of these disorders for several genes related to vascular, neuronal and neuroendocrine functions. A potential role as a therapeutic target is now emerging for some of these genes. The main purpose of this review is to describe new advances in our knowledge regarding the role of MTHFR, KCNK18, TRPV1, TRPV3 and HCRTR genes in primary headache disorders. Involvement of these genes in primary headaches, as well as their potential role in the therapy of these disorders, will be discussed.
J Headache Pain 2013 Jul 12
PMID:Genes and primary headaches: discovering new potential therapeutic targets. 2384 1


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