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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms underlying the pathogenesis of migraine and their possible association with serotonin (5-hydroxytryptamine; 5-HT) have not yet been elucidated. One of the major obstacles in achieving this goal is the lack of information on the mechanisms by which the monoamine could possibly trigger and/or modulate the basic pathophysiological features of the condition, that is, cranial vasodilatation and neurogenic inflammation. This information should provide a useful theoretical framework to insight the nature of the postulated fundamental triggering mechanism in the brain that ultimately results in head pain. Novel avenues for research and drug development may be envisaged upon the recent observations showing that 5-HT is actually able to produce vasodilatation of intra- and extra-cranial blood vessels through a mechanism pharmacologically resembling the 5-HT(7) receptor type, and that the messenger RNA (mRNA) encoding for this receptor is highly expressed in cranial vessels. Other lines of evidence have suggested that the 5-HT(7) receptor may play an excitatory role in neuronal systems and that it may be involved in hyperalgesic pain and neurogenic inflammation. On the basis of these observations, it is proposed that the 5-HT(7) receptor may well represent a link between the abnormal phenomena of 5-HT processing and neurotransmission that are observed in migraine patients, and the vascular and neurogenic alterations that account for migraine headache. This view is supported by the fact that most of the migraine prophylactic 5-HT receptor antagonists display relatively high affinity for the 5-HT(7) receptor, which significantly correlates with their pharmaceutically active oral doses.
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PMID:Is the 5-HT(7) receptor involved in the pathogenesis and prophylactic treatment of migraine? 1193 86

In order to investigate the c-fos response within the trigeminal nucleus caudalis (Sp5C) after noxious meningeal stimulation, capsaicin (0.25, 0.5, 1 and 5 nmol) was administered intracisternally in urethane (1 g/kg) and alpha-chloralose (20 mg/kg) anaesthetized male mice. Capsaicin induced a robust and dose-dependent c-fos-like immunoreactivity (c-fos LI) within Sp5C. C-fos LI was observed within laminae I and II of the entire brain stem from the area postrema to C2 level, being maximum at the decussatio pyramidum level. The area postrema, solitary tract, medullary and lateral reticular nuclei were also labelled. The 5-hydroxytryptamine(1B/1D/1F) receptor agonist sumatriptan (0.01, 0.1, 1 and 10 mg/kg), administered intraperitoneally 15 min before capsaicin stimulation (1 nmol), decreased the c-fos response within Sp5C, but not within solitary tract. The novel specific 5-hydroxytryptamine1F agonist LY 344864 (0.1 and 1 mg/kg, i.p.) significantly decreased the c-fos LI within the Sp5C as well. These findings suggest that intracisternally administered capsaicin activates the trigeminovascular system and that the pain neurotransmission can be modulated by 5-hydroxytryptamine(1B/1D/1F) receptors in mice. Thus, the availability of this model in mice, taken together with the possibility of altering the expression of specific genes in this species, may help to investigate further the importance of distinct proteins in the neurotransmission of cephalic pain.
Cephalalgia 2002 Jun
PMID:5-Hydroxytryptamine(1B/1D) and 5-hydroxytryptamine1F receptors inhibit capsaicin-induced c-fos immunoreactivity within mouse trigeminal nucleus caudalis. 1211 Jan 14

Six children developed severe daily migraine-type headaches during cancer treatment. In addition to chemotherapy drugs, all received daily doses of ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist. 5-Hydroxytryptamine is considered to play a central role in migraine pathogenesis, and ondansetron may have caused headaches by producing 5-hydroxytryptamine dysfunction in the brain. All six children had either a personal or a family history of migraine, and this may be a risk factor for developing ondansetron-associated migraine-type headaches. Ondansetron-induced headaches respond to withholding the drug and to standard antimigraine medications, but further study of a larger group of patients is required to confirm this impression.
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PMID:Migraine-type headaches in children receiving chemotherapy and ondansetron. 1258 31

The effects of donitriptan on systemic arterial-jugular venous oxygen saturation difference were evaluated in pentobarbitone-anesthetized pigs. Oxygen and carbon dioxide partial pressures in systemic arterial and jugular venous blood as well as hemoglobin oxygen saturation were determined by conventional blood gas analysis. Vehicle (40% polyethyleneglycol in saline, n = 9) or donitriptan (0.01, 0.04, 0.16, 0.63, 2.5, 10, and 40 microg/kg, n = 7) were cumulatively infused over 15 min/dose. The involvement of 5-hydroxytryptamine(1B) (5-HT(1B)) receptors was assessed in the presence of the 5-HT(1B/1D) receptor antagonist, GR 127935. Donitriptan decreased markedly and dose dependently jugular venous oxygen saturation [ED(50) 0.5 (0.3-1.1) microg/kg], in parallel with increases in carotid vascular resistance [ED(50) 0.9 (0.7-1.1) microg/kg]. Since arterial oxygen saturation and partial pressure remained unchanged, donitriptan significantly increased arteriovenous oxygen saturation difference from 0.63 microg/kg (maximal variation: 57 +/- 18%, P < 0.05 compared with vehicle). Unexpectedly, donitriptan from 2.5 microg/kg induced marked and significant increases in carbon dioxide partial pressure (pVCO(2)) in venous blood (maximal increase 18.8 +/- 5.7%; P < 0.05 compared with vehicle). Pretreatment with GR 127935 (0.63 mg/kg, n = 5) abolished the fall in venous oxygen saturation and the increase in carotid vascular resistance and reduced the increases in pVCO(2) induced by donitriptan. The results demonstrate that donitriptan, via 5-HT(1B) receptor activation, decreases the oxygen saturation of venous blood draining the head, concomitantly with cranial vasoconstriction. Since donitriptan also increased pVCO(2), an effect upon cerebral oxygen consumption and metabolism is suggested in addition to cranial vasoconstriction, which may be relevant to its headache-relieving effects.
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PMID:Donitriptan selectively decreases jugular venous oxygen saturation in the anesthetized pig: further insights into its mechanism of action relevant to headache relief. 1260 2

Even though the underlying mechanisms for the pathophysiology of migraine attacks are not completely understood, little doubt exists that the headache phase is explained by dilatation of cranial, extracerebral blood vessels. In this context, experimental models predictive for anti-migraine activity have shown that both triptans and ergot alkaloids, which abort migraine headache, produce vasoconstriction within the carotid circulation of different species. In contrast to the well-established role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT1B receptors in the common carotid vascular bed, the role of alpha-adrenoceptors and their subtypes has been examined only relatively recently. Using experimental animal models and alpha1- and alpha2-adrenoceptor agonists (phenylephrine and BHT933, respectively) and antagonists (prazosin and rauwolscine, respectively), it was shown that activation of either receptor produces a cranioselective vasoconstriction. Subsequently, investigations employing relatively selective antagonists at alpha1- (alpha1A, alpha1B, alpha1D) and alpha2- (alpha2A, alpha2B, alpha2C) adrenoceptor subtypes revealed that specific receptors mediate the carotid haemodynamic responses in these animals. From these observations, together with the potential limited role of alpha1B- and alpha2C-adrenoceptors in the regulation of systemic haemodynamic responses, it is suggested that selective agonists at these receptors may provide a promising novel avenue for the development of acute anti-migraine drugs.
Cephalalgia 2003 May
PMID:Possible role of alpha-adrenoceptor subtypes in acute migraine therapy. 1271 41

Triptans, beginning with sumatriptan, have revolutionized the treatment of migraine. New triptans in several formulations will soon become available in the United States. Although the similarities of these 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists outweigh their differences, important differences in pharmacokinetics and clinical responses do exist. Subcutaneous sumatriptan has the most rapid onset of action and greatest efficacy but the most adverse effects. Intranasal sumatriptan also has rapid onset of action, but at 2 hours its efficacy is comparable to that of oral zolmitriptan. Of the oral triptans, rizatriptan seems to have the greatest early efficacy. Both rizatriptan and zolmitriptan are now available as rapidly dissolving wafers. Almotriptan, the newest of the triptans, has a response rate similar to that of oral sumatriptan and may produce fewer adverse effects. Naratriptan and frovatriptan, with their slow onset, high tolerability, and long half-lives, may have a role in aborting prolonged migraine attacks and in headache prevention. Eletriptan at higher doses (80 mg) has a response rate approaching that of rizatriptan but may be limited by potential side effects. The many triptans available offer the opportunity to individualize migraine treatment, depending on the patient's attack characteristics, tolerance, and preferences.
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PMID:Comparative aspects of triptans in treating migraine. 1273 16

Granisetron (Kytril, Roche) is a 5-hydroxytryptamine 3 (5-HT(3))-receptor antagonist indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin. Its indication expanded in August 2002, with approval from the FDA for the prevention and treatment of postoperative nausea and vomiting. Granisetron strongly and selectively binds to the 5-HT(3) receptor with a binding constant of 0.26 nM and exhibits a 4000 - 40,000 times greater binding affinity for the 5-HT(3) receptor than other binding sites, including other 5HT subtypes and adrenergic, histaminergic and opioid receptors. Its selectivity to the 5-HT(3) receptor over other receptor types is > 1000:1. Granisetron noncompetitively binds to the 5-HT(3) receptor and is associated with a long duration of action as shown by the inhibition of a 5-HT axonal response flare for up to 24 h. Granisetron is unique among the 5-HT(3)-receptor antagonists because it is not metabolised via the cytochrome P450 (CYP) 2D6 pathway and is, therefore, less susceptible to variation in patient response because of factors such as pharmacogenomic differences. Granisetron and other 5-HT(3)-receptor antagonists are first-line agents for acute chemotherapy-induced nausea and vomiting (CINV), whereas combination therapy with 5-HT(3)-receptor antagonists, dexamethasone and neurokinin (NK)-1 receptor antagonism (i.e., with the recently approved aprepitant) is an effective approach to prevent delayed CINV. Granisetron has been shown to be an effective within-class rescue antiemetic for prophylactic failures, which may be linked to its pharmacological properties including non-competitive, insurmountable binding to the 5-HT(3) receptor. As with other 5-HT(3)-receptor antagonists, granisetron is well-tolerated with adverse events of mild severity including headache, asthenia and constipation. Overall, data demonstrate that granisetron is an efficacious, safe and cost-effective member of the 5HT(3)-receptor antagonist class for the prevention of CINV.
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PMID:Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. 1294 86

Estrogen exerts a strong influence on episodic headaches, such as migraine and tension-type headache. A relationship between sex hormones and chronic daily headache (CDH) is less well established. However, similarities between episodic and CDH suggest that estrogen also may significantly influence CDH. Pathophysiologic studies of CDH identify neurochemical abnormalities similar to those influenced by estrogen in episodic headache, such as aberrant 5-hydroxytryptamine activity. In addition, gender differences in CDH prevalence in pediatric and adult populations support a hormonal influence. Few studies have evaluated the ability of gynecologic events, such as menses, to influence CDH.
Curr Pain Headache Rep 2004 Feb
PMID:Estrogen and chronic daily headache. 1473 85

Migraine is a very common disorder. In Japan, an estimated 8.4% of population experience migraine, but most of them go undiagnosed and undertreated. Recent advances in basic and applied clinical neuroscience have led to the development of sumatriptan, a new class of selective serotonin (5-hydroxytryptamine (5-HT)) receptor agonists that activate 5-HT 1B/1D receptors. Following sumatriptan several other triptans were produced. They have three main mechanism of action: cranial vasoconstriction, peripheral trigeminal inhibition, and inhibition of transmission through second order neurons of the trigeminocervical complex. Even in our country, we can now use three kinds of triptans, which are very effective medicine against acute migraine with a well-developed scientific rationale. Despite the higher price, triptans were preferred over ergots in most patients. Recently Limmroth et al reported a prospective study for medication overuse headache (MOH) in 98 patients. The mean critical duration until onset of MOH was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (4.8 years). The mean critical monthly intake frequencies was lowest for triptans (18 single doses per month), higher for ergots (37), and highest for analgesics (114). We should keep in mind that overuse of triptans leads to MOH faster and with lower dosages compared with ergots and analgesics.
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PMID:[Pitfall in migraine treatment]. 1515 55

A new experimental human model of myofascial pain using intramuscular infusion of a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and prostaglandin E2 was applied to patients with episodic tension-type headache (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15 healthy controls completed the randomized, balanced, double-blinded, placebo-controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain quality were recorded. The combination induced a moderate and prolonged pain in both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P = 0.001). Patients reported more pain than controls both after the combination (P = 0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas pain quality and hyperalgesia were similar after the combination compared with placebo in the two groups. Due to side-effects nine subjects did not complete the study. The increased pain response, but similar qualitative pain perception, in ETTH patients may be explained by sensitization of peripheral nociceptors even though central mechanisms may also be involved.
Cephalalgia 2004 Jun
PMID:Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimental model of myofascial pain. 1515 56


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