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)

A 56-year-old man with fever, headache, cough and sputum was admitted to another clinic. Chest X-ray examination revealed infiltrates in the upper lobe of the right lung. Cefem and aminoglycoside therapy was not effective, and the infiltrates migrated from the right upper lobe to the right middle and lower lobes and then to the left lung. He was transferred to our clinic, and laboratory data showed that CRP was 6+; ESR, 119 mm/1 h; WBC, 3000/mm3; and CAR, 512. The tentative diagnosis of atypical pneumonia was based on the positive agglutination test for Legionella pneumophila, and treatment with erythromycin, minocycline and rifampicin resulted in alleviation of symptoms and resolution of the infiltrates in the lungs. Complement fixation titer for Chlamydia was 128 at admission and was elevated to 512 after 2 weeks. Indirect fluorescent antibody for Legionella was negative. Transient liver dysfunction was also observed.
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PMID:[A case of psittacosis with migratory infiltrates]. 162 83

1. The purpose of this study was to investigate the mechanism of nicotine-evoked relaxation of the guinea-pig isolated basilar artery and to study the effects of drugs associated with the aetiology or treatment of migraine on the nicotine response. 2. The guinea-pig isolated basilar artery, pre-contracted with prostaglandin F2alpha (PGF2alpha), in the presence of atropine (3 microM) and guanethidine (3 microM), relaxed on addition of nicotine (0.1 mM) in approximately 50% of preparations. The responses to nicotine were of short duration and blocked in preparations pre-treated for 10 min with capsaicin (1 microM) and are therefore probably a consequence of the stimulation of trigeminal C fibre terminals. 3. Responses to nicotine were reduced in the presence of 5-carboxamidotryptamine, 5-hydroxytryptamine and sumatriptan in that order of potency. This is consistent with a 5-HT1 receptor mechanism. These agonists evoked small additional contractions in vessels pre-contracted with PGF2alpha. 4. Indomethacin (0.3-10 microM), aspirin (10-30 microM), and nitro-L-arginine methyl ester (L-NAME, 0.1 mM) reduced nicotine-evoked relaxation of the basilar artery, suggesting the involvement of both nitric oxide and cyclo-oxygenase products in this response. 5. Progesterone (1 microM) markedly reduced the response to nicotine, a possible reflection of the ion channel blocking activity of high concentrations of this compound. 6. The guinea-pig basilar artery is a preparation in which the effects of drugs on responses to stimulation of trigeminal nerve terminals can be studied in vitro and may thus be of interest in assessing the actions of drugs used in treatment of headache.
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PMID:The inhibition of nicotine-evoked relaxation of the guinea-pig isolated basilar artery by some analgesic drugs and progesterone. 1019 81

Primary neurovascular headaches, such as migraine and cluster headache probably involve activation of trigeminovascular pain structures projecting to the trigeminocervical complex of neurons in the caudal brain stem and upper cervical spinal cord. It has recently been demonstrated that blockade of the synthesis of nitric oxide (NO) by an NO synthesis inhibitor can abort acute migraine attacks and thus it is of interest to determine whether there is an influence of NO generation on trigeminocervical neurons. Cats were anaesthetised with alpha-chloralose (60 mg/kg, i.t.). supplemental 20 mg/kg, intravenously (i.v.)) and halothane for surgery (0.5-3% by inhalation). A circular midline craniotomy was performed to isolate the superior sagittal sinus (SSS) for electrical stimulation (0.3 Hz, 150 V, 250 micros duration for 2 h). Two groups were compared, one stimulated after administration of vehicle and the other stimulated after administration of N(G)-nitro-L-arginine methylester (L-NAME: 100 mg/kg, i.v.). After stimulation of the SSS Fos immunoreactivity was observed in lamina I/IIo of the trigeminal nucleus caudalis and dorsal horns of C1 and C2 to a median total of 136 cells (range 122-146). After L-NAME treatment Fos expression was significantly reduced to 40 cells (24-54; P < 0.02). In conclusion, inhibition of NO synthesis L-NAME markedly reduces Fos expression in the trigeminocervical complex of the cat. These data taken together with the clinical observations of the effect of NO synthesis blockade in migraine suggest a role for NO generation in mediating nociceptive transmission in acute migraine.
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PMID:Fos expression in the trigeminocervical complex of the cat after stimulation of the superior sagittal sinus is reduced by L-NAME. 1046 1

1. Nitric oxide (NO) has been proposed to be a key molecule in the pathogenesis of migraine pain and other headaches that are linked to vascular disorders. Several lines of evidence indicate that the meningeal vascularization is crucially involved in the generation of these headaches. In an experimental model in the rat a dominating role of calcitonin gene-related peptide (CGRP) in causing neurogenic vasodilatation and increased blood flow has been shown. The aim of the present study was to clarify the role of NO in this model with regard to the meningeal blood flow. 2. The blood flow in and around the medial meningeal artery (dural arterial flow) was recorded in the exposed parietal dura mater encephali of barbiturate anaesthetized rats using laser Doppler flowmetry. Local electrical stimulation of the dura mater (pulses of 0.5 ms delivered at 7.5 - 17.5 V and 5 or 10 Hz for 30 s) caused temporary increases in dural arterial flow for about 1 min that reached peaks of 1.6 - 2.6 times the basal flow. The effects of NO synthase (NOS) inhibitors on the basal flow and the electrically evoked increases in flow were examined. 3. Systemic (i. v.) administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) at cumulative doses of 10 and 50 mg kg(-1) lowered the basal flow to 87 and 72%, respectively, of the control and reduced the evoked increases in blood flow to 82 and 44% on an average. Both these effects could partly be reversed by 300 mg kg(-1) L-arginine. The systemic arterial pressure was increased by L-NAME at both doses. Injection of the stereoisomer D-NAME at same doses did not change basal flow and evoked increases in flow. 4. 4. Topical application of L-NAME (10(-4) - 10(-2) M) was effective only at the highest concentration, which caused lowering of the basal blood flow to 78% of the control; the evoked increases in flow were not changed. Topical application of 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a specific inhibitor of the inducible NOS, at concentrations of 10(-4) - 10(-2) M lowered the basal flow to 89, 87.5 and 85%, respectively, but did not significantly change the evoked flow increases. Same concentrations of 7-nitroindazole monosodium salt (7-NINA), a specific inhibitor of the neuronal NOS, had no significant effects on basal flow and evoked increases in flow. 5. It is concluded that NO is involved in the maintenance of the basal level of dural arterial blood flow as well as in the electrically evoked flow increases, which have been shown to be mainly mediated by CGRP released from dural afferent fibres. The most important source of NO is probably the endothelium of dural arterial vessels. The synergistic effect of NO and CGRP on the stimulated blood flow may be in part due to a NO mediated facilitation of the CGRP release.
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PMID:Involvement of nitric oxide in the modulation of dural arterial blood flow in the rat. 1074 95

Nitric oxide is thought to control transmitter release and neuronal activity in the spinal dorsal horn and the spinal trigeminal nucleus, where nociceptive information from extra- and intracranial tissues is processed. Extracellular impulse activity was recorded from neurons in the rat spinal trigeminal nucleus with afferent input from the cranial dura mater. In contrast to the inactive isomer D-NAME, infusion of the nitric oxide synthase inhibitor L-NAME (20 mg/kg) significantly reduced neuronal activity and increased systemic blood pressure. It is concluded that nitric oxide production contributes to the ongoing activity of sensitized neurons in the spinal trigeminal nucleus. The results suggest that nitric oxide may be involved in the generation and maintenance of primary headaches such as migraine.
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PMID:Nitric oxide synthase inhibition lowers activity of neurons with meningeal input in the rat spinal trigeminal nucleus. 1259 35

The compound m-chlorophenylpiperazine (mCPP), which is known to trigger migraine-like head pain in some subjects, was evaluated for its ability to induce dural plasma protein extravasation (PPE) in guinea pigs. Intravenous mCPP dose-dependently increased PPE. This effect was inhibited by non-selective 5-HT2 receptor antagonists (methysergide, LY53857, LY215840), by a peripherally restricted 5-HT2 receptor antagonist (xylamidine) and by a 5-HT2B selective receptor antagonist (LY202146). These data suggests that peripheral 5-HT2B receptors mediate mCPP-induced PPE. The nitric oxide synthase inhibitor L-NAME and 5-HT1 agonist sumatriptan also blocked mCPP-induced PPE, suggesting a role for nitric oxide (NO) and the trigeminal system, respectively. NO release has been linked to activation of the 5-HT2B receptor on the vascular endothelium. However, LY202146 did not block PPE induced by electrical stimulation of the trigeminal ganglion. These data are consistent with activation of peripheral 5-HT2B receptors initiating PPE and the theory that selective 5-HT2B antagonists might be effective prophylactic therapies for migraine.
Cephalalgia 2003 Mar
PMID:Neurogenic dural protein extravasation induced by meta-chlorophenylpiperazine (mCPP) involves nitric oxide and 5-HT2B receptor activation. 1260 68

Neuropeptide release and the expression of c-fos like immunoreactivity (c-fos LI) within trigeminal nucleus caudalis neurons (TNC) are activation markers of the trigeminal nerve system. Glyceryltrinitrate (GTN) is believed to stimulate the trigeminal nerve system, thereby causing headache. We examined the effects of a 30 min NO-donor infusion on CGRP release in jugular vein blood and c-fos LI within TNC of the rat. GTN (2 and 50 microg/kg/min) or NONOate infusion (25 nmol/kg/min) did not cause any CGRP release during and shortly after infusion, whereas administration of capsaicin resulted in strongly increased CGRP levels. GTN infusion (2 microg/kg/min for 30 min) did not lead to enhanced c-fos LI after 2 h and 4 h, whereas capsaicin infusion caused a time- and dose-dependent expression of c-fos LI within laminae I and II of the TNC. Surprisingly, GTN attenuated capsaicin-induced c-fos expression by 64%. The nitric oxide synthase (NOS) inhibitor L-NAME (5 and 50 mg/kg) reduced capsaicin-induced c-fos LI dose dependently (reduction by 13% and 59%). We conclude that GTN may lead to headaches by mechanisms independent of CGRP release from trigeminal nerve fibres. GTN doses comparable to those used in humans did not activate or sensitize the trigeminal nerve system. Both GTN and L-NAME reduced capsaicin-induced c-fos LI. This is most likely due to a feedback inhibition of nitric oxide synthases, which indicates that the c-fos response to capsaicin within TNC is mediated by NO dependent mechanisms.
Cephalalgia 2005 Mar
PMID:CGRP release and c-fos expression within trigeminal nucleus caudalis of the rat following glyceryltrinitrate infusion. 1568 99

Calcitonin gene-related peptide (CGRP), nitric oxide (NO) and histamine are implicated in primary headaches but their role in vascular and nociceptive events in the dura mater is not well described. In an in vitro preparation of the hemisected rat skull, CGRP and histamine release from the cranial dura was measured using enzyme-linked immunoassays. While the NO donator NONO(ate) (10(-4) M) was without effect, CGRP (10(-5) M) induced considerable histamine release from the rat cranial dura, which was blocked by the CGRP receptor antagonist CGRP(8-37) (10(-5) M). Conversely, histamine (10(-4) M) did not stimulate CGRP release. In vitro recordings from single rat meningeal afferents showed that only one of 12 mechanically identified units but several mechanically insensitive units responded to histamine (up to 10(-5) M). Increases in meningeal blood flow after histamine application (10(-4) M) to the rat cranial dura remained unchanged during CGRP receptor blockade with CGRP(8-37), inhibition of NO synthesis with L-NAME (20 mg/kg i.v.) and H(3) receptor blockade with thioperamide (10(-4) M). We conclude that histamine produces direct vasodilatation and activates a subset of largely non-mechanically sensitive, non-CGRP containing afferents in the rat meninges. Histamine is released from meningeal mast cells which are stimulated by CGRP. Similar mechanisms may be involved in the pathogenesis of headaches.
Cephalalgia 2007 Jun
PMID:Interaction of calcitonin gene-related peptide, nitric oxide and histamine release in neurogenic blood flow and afferent activation in the rat cranial dura mater. 1744 73

Neurogenic inflammation of the dura mater encephali has been suggested to contribute to the mechanisms of meningeal nociception and blood flow regulation. Recent findings demonstrated that the rat dura mater is innervated by trigeminal capsaicin-sensitive peptidergic nociceptive afferent nerves which mediate meningeal vascular responses through activation of the transient receptor potential vanilloid type 1 (TRPV1) receptor. The present work explored the functional significance of the capsaicin-sensitive subpopulation of dural afferent nerves via their contribution to the meningeal vascular responses evoked through activation of the proteinase-activated receptor 2 (PAR-2). The vascular responses of the dura mater were studied by laser Doppler flowmetry in a rat open cranial window preparation. Topical applications of trypsin, a PAR-2-activator, or Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)), a selective PAR-2 agonist peptide, resulted in dose-dependent increases in meningeal blood flow. The SLIGRL-NH(2)-induced vasodilatation was significantly reduced following capsaicin-sensitive afferent nerve defunctionalization by prior systemic capsaicin treatment and by pretreatment of the dura mater with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37). Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) an unspecific inhibitor of nitric oxide (NO) production, but not 1-(2-trifluoromethylphenyl) imidazole (TRIM), a neuronal NO synthase inhibitor, also inhibited the vasodilator response to SLIGRL-NH(2). The vasodilator responses elicited by very low concentrations of capsaicin (10 nM) were significantly enhanced by prior application of SLIGRL-NH(2). The present findings demonstrate that activation of the PAR-2 localized on capsaicin-sensitive trigeminal nociceptive afferent nerves induces vasodilatation in the dural vascular bed by mechanisms involving NO and CGRP release. The results indicate that the PAR-2-mediated activation and sensitization of meningeal capsaicin-sensitive C-fiber nociceptors may be significantly implicated in the pathophysiology of headaches.
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PMID:Involvement of capsaicin-sensitive afferent nerves in the proteinase-activated receptor 2-mediated vasodilatation in the rat dura mater. 1936 18

Mentha pulegium is common known as "poleo" and used for the treatment of diarrhea, headache and cough in Mexican traditional medicine. Organic extracts from aerial parts were evaluated to determine their spasmolytic action on rat isolated ileum test. Hexanic (HEMp), dichloromethanic (DEMp) and methanolic (MEMp) extracts induced a concentration-dependent (0.97 to 1000 microg/mL) antispasmodic effect on spontaneous contractions. DEMp was the most active extract; therefore, spasmolytic mechanism was investigated. This extract (200 microg/mL) induced a significant depression on cumulative concentration-response curve for carbachol and serotonin (P<0.05). Besides, extract decreased and shifted to the right KCl- and CaCl2-induced contraction curves. Moreover, pre-incubation with chlorpromazine (0.001 mM) shifted to the left the relaxant curve. Pre-treatment with L-NAME (1 mM), papaverine (0.01 mM), teophylline (0.01 mM), TEA (1 mM) and glybenclamide (0.1 mM) did not produced any changed of the relaxant curves of DEMp. Findings indicate that dichloromethanic extract of M. pulegium induced its spasmolytic effect through Ca2+-influx blockade, which may explain its traditional use against diarrhea.
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PMID:Spasmolytic effect of Mentha pulegium L. involves ionic flux regulation in rat ileum strips. 2055 91


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