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)

Activation of the cAMP/protein kinase A (PKA) second messenger cascade has been implicated in the induction of mechanical hyperalgesia by inflammatory mediators. We examined the role of this cascade in mechanical sensitization of nociceptive neurons that innervate the meninges, a process thought to be involved in the pathophysiology of headache syndromes such as migraine. Single unit activity was recorded in the trigeminal ganglion from 40 mechanosensitive dural afferents (conduction velocitity: 0.3-6.6 m s(-1)) and nine mechanically insensitive dural afferents (MIAs) (conduction velocitity: 0.3-2.8 m s(-1)) while stimulating the dura with a servo force-controlled stimulator or von Frey monofilaments, respectively. Local application to the dura of dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP, 100 microM), a stable membrane-permeant cAMP analogue, produced mechanical sensitization in the majority of mechanosensitive units (19/29, 66 %). Two distinct patterns of mechanical sensitization were observed. Thirty-eight per cent of the units exhibited only a decrease in threshold (TH group), while 28 % showed only an increase in suprathreshold responses (STH group). dbcAMP also induced mechanosensitivity in the majority of MIA units (6/9, 67 %). dbcAMP-induced sensitization was blocked by the PKA inhibitors, Rp-cAMP (1 mM) and H-89 (100 microM). A mixture of inflammatory mediators induced both components of sensitization in the majority of mechanosensitive units tested. However, in each unit, PKA inhibitors blocked only one of the two effects (either TH or STH). Units that were classified as TH or STH also differed in their baseline stimulus-response slopes, thresholds and conduction velocities. These findings implicate the cAMP-PKA cascade in sensitization of dural mechanonociceptors and suggest that this cascade may produce sensitization through at least two different mechanisms operating in separate neuronal populations.
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PMID:Distinct sensitizing effects of the cAMP-PKA second messenger cascade on rat dural mechanonociceptors. 1179 Aug 14

Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. Here we establish a link between migraine aura and headache by demonstrating that cortical spreading depression, implicated in migraine visual aura, activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache. Cortical spreading depression caused long-lasting blood-flow enhancement selectively within the middle meningeal artery dependent upon trigeminal and parasympathetic activation, and plasma protein leakage within the dura mater in part by a neurokinin-1-receptor mechanism. Our findings provide a neural mechanism by which extracerebral cephalic blood flow couples to brain events; this mechanism explains vasodilation during headache and links intense neurometabolic brain activity with the transmission of headache pain by the trigeminal nerve.
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PMID:Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. 1182 89

We describe the case of a 54-year-old woman with a clinical diagnosis of Churg-Strauss syndrome (CSS). The patient had a fever of unknown origin, severe headache, progressing left ophthalmoplegia, and visual acuity disturbance. MR imaging revealed diffuse and thick hypointense lesions on T2-weighted images in the frontal meninges and anterior falx cerebri with diffuse enhancement. Similar lesions were also detected in the left superior ophthalmic fissure to the cavernous sinus. Nodular lesions in the fourth ventricle, which might have been the cause of hydrocephalus, were hypointense on T2-weighted images. These MR imaging findings suggested remote granulomatous involvement in the meninges and choroid plexus associated with CSS. To our knowledge, remote meningeal involvement in association with CSS has not been previously reported.
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PMID:Intracranial meningeal involvement in Churg-Strauss syndrome. 1184 45

Migraine and tension-type headaches are two of the most common types of primary headache disorders in children. Migraine is a primary central nervous system disorder characterized by triggered or spontaneous episodes of activation of trigemino-vascular complex, neurogenic inflammation around vessels and meninges, and stimulation of the peripheral and central pain pathways of the trigemino-cervical complex. The triptans, by their selective agonistic action on 5-HT1B/1D receptors, are very effective in the treatment of migraine pain and associated symptoms. Early studies on the safety and efficacy of triptans in the management of childhood migraine show encouraging results. We propose a stratified-care model for the management of migraine in children, and discuss pharmacotherapy based on the pathophysiologic mechanisms of migraine pain. Management of tension-type headaches requires comprehensive medical and psychologic evaluation and an individualized approach for a successful outcome.
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PMID:Treatment of childhood headaches. 1189 10

Magnetic resonance imaging (MRI) has allowed us to establish a set of radiologic signs associated with intracranial hypotension syndrome. Findings are partly influenced by cerebral displacement. Intracranial hypotension syndrome is characterized by a decrease in cerebrospinal fluid (CSF) pressure to less than 60 mm H2O associated with occipital headache radiating to the frontal and temporal zones. For diagnostic purposes, the most common cause is anesthetic or therapeutic dural puncture, although spontaneous CSF leakage can occur. CSF protein and lymphocyte counts may be high, while the cranial meninges biopsy is normal. MRI images may show a descended brain, taking the start of the sylvian aqueduct and the location of the cerebellar amygdalae as points of reference; diminished size of the subarachnoidal cisterns and occasionally of the cerebral ventricles; meningeal enhancement from increased uptake of the contrast solution; subdural hygromas and hematomas; and pituitary enlargement. Paraspinal fluid and dilated epidural veins may be observed. Radiologic images and clinical signs are related. When CSF pressure is very low, there is greater meningeal enhancement, subdural collection and cerebral displacement. Findings gradually disappear as symptoms diminish. The signs and symptoms that might develop during intracranial hypotension syndrome vary according to the brain structure that might be affected during descent, repositioning and the traction of anchoring structures. MRI allows the degree of cerebral and spinal involvement to be ascertained, to predict whether resolution of the clinical picture will be early or late and to visualize the effect of approaches to reducing CSF leakage.
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PMID:[Magnetic resonance in dural post-puncture headache in patient with cerebrospinal fluid hypotension]. 1202 53

We presented a patient of spontaneous intracranial hypotension (SIH), in which radionuclide cisternography demonstrated multiple CSF leaks. A 51-year-old previously healthy woman awoke with a severe headache and nausea that were almost completely relieved by lying flat (day 1). The headache was not relieved by analgesics. On day 10, she visited our clinic. Neurological examination showed no abnormalities. A lumbar puncture revealed an opening pressure of 50 mmH2O, protein level of 64 mg/dl, 21 erythrocytes 21/microliter, and 4 lymphocytes/microliter. Cranial MRI on day 11 with gadolinium infusion demonstrated diffuse thickening and enhancement of the meninges. No signs of venous sinus thrombosis were identified. There was no downward displacement of the cerebellar tonsils. Indium-111 radionuclide cisternography demonstrated early accumulation of the tracer in the urinary bladder and CSF leakage at the upper thoracic level on the left side, at the lower thoracic level on both sides, and at the lumbar level. It is noteworthy that the scintigram taken 4 hours after tracer injection demonstrated CSF leakage at the injection site but not in the upper thoracic area. The patient kept sitting for about 20 minutes just before the images were obtained. Spinal MRI did not show meningeal diverticulum and epidural fluid collection. Ten days of bed-rest and transfusion failed to relieve the headache. Epidural patching with 7 ml of autologous blood performed at the Th2/3 interspace partially relieved the headache. Five days later, a second epidural patching was performed at Th11/12, which was slightly effective. A third epidural patching at L3/4 was ineffective. On day 32, a fourth epidural patching was performed at Th1/2 while the patient was lying down on her left side. The postural headache disappeared. Repeated cranial MRI with gadolinium infusion performed on day 47 showed resolution of the abnormal findings. To our knowledge, this is the second case report of SIH with double CSF leaks. To localize multiple leaks, radionuclide cisternography should be performed with a patient in various positions just before images are obtained.
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PMID:[A case of spontaneous intracranial hypotension with simultaneous CSF leaks at the upper and lower thoracic levels]. 1208 Jun 8

The aim of the study was to present rarely reported neurologic complications in Nijmegen breakage syndrome. A 13-year-old female was referred because of chronic progressive headaches. There were dysmorphic features on physical examination, which suggested a diagnosis of chromosomal instability syndrome. The results of genetic and immunologic examinations confirmed the diagnosis. Cerebral magnetic resonance imaging revealed an 8 mm thickening of the meninges over the left hemisphere, corresponding with a chronic inflammatory condition, and symptoms of left cavernous thrombophlebitis were detected. Cerebrospinal fluid examination and an infusion test demonstrated disorders in its absorption. Antibiotic, anticoagulant and cerebral edema treatment was given and after 1 week improvement was observed. Regression of symptoms occurred after 14 days.
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PMID:Cavernous sinus thrombophlebitis in Nijmegen breakage syndrome. 1216 Sep 77

Myofibroblastoma is a rare type of benign mesenchymal tumor; only two cases of intracranial myofibroblastoma have been reported in the literature. The authors report on the case of a 34-year-old woman with a myofibroblastoma in the suprasellar region who presented with the complaint of sudden onset of headache followed within 2 weeks by progressively worsening visual disturbance. Computerized tomography scanning demonstrated a mixed low- and high-density mass in the suprasellar region and contrast-enhanced magnetic resonance imaging revealed the mass to be of mixed intensity with heterogeneous enhancement. The tumor was subtotally removed via a right frontobasal translamina-terminalis approach and her vision improved immediately. Histologically, the tumor was characterized by alternating areas of spindle-shaped and round cells that were separated by collagen fibers. The diagnosis of myofibroblastoma was based on the tumor's intense immunoreactivity for alpha-smooth-muscle actin and the ultrastructural identification of myofibroblasts. The tumor was thought to have originated from the meninges in the suprasellar region.
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PMID:Myofibroblastoma in the suprasellar region. Case report. 1245 45

Nitric oxide (NO) and calcitonin gene-related peptide (CGRP), potent vasodilators in the meninges,may be involved in the pathophysiology of vascular headaches such as migraine pain. NO donators can provoke headache attacks in migraineurs and increased levels of CGRP have been found in the venous outflow from the head during migraine attacks. We therefore examined the effect of both NO and CGRP on dural blood, a process which may parallel nociceptive processes in the meninges. 1. Arterial blood flow was measured in the exposed dura mater encephali of the rat using laser Doppler flowmetry. Local application of different NO donors (SNAP,NONOate, and NOC-12) caused dose-dependent increases in meningeal blood flow. CGRP(8-37) at 10(-4) M did not significantly change the basal flow but attenuated increases in blood flow caused by the NO donors at concentrations of 10(-5)-10(-3) M.2. In another series of experiments, the hemisected skulls of adult Wistar rats, complete with intact dura mater, were filled with oxygenated synthetic interstitial fluid (SIF) and the CGRP content of this fluid was assessed every 5 min. When the NO donator NONOate, at concentrations of 10(-5)-10(-3) M, was added to the SIF, or when the SIF was bubbled with NO gas (1000 ppm in N(2) atmosphere) instead of carbogen, CGRP release increased in a concentration-dependent manner. We conclude that the vasodilatory effect of NO that causes increased meningeal blood flow is in part the result of both stimulating the release of CGRP and promoting the vasodilatory action of CGRP. Since NO donors such as nitroglycerin are known to provoke headache and CGRP is released during migraine pain, the NO-stimulated CGRP release may be relevant for the development of vascular headaches that are accompanied by meningeal hyperaemia.
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PMID:[Neuropeptide release in the dura mater encephali in response to nitric oxide--relevance for the development of vascular headaches?]. 1278 84

Neurogenic inflammation of the meninges, expressed in plasma extravasation and vasodilatation, putatively contributes to certain types of headache. Both, non-steroidal antiinflammatory drugs (NSAIDs) and serotonin-1 (5-HT1) receptor agonists are similarly effective antimigraine drugs but their mechanism of action is unclear. The clinical observation that sumatriptan lowered plasma levels of calcitonin gene-related peptide (CGRP), found increased during migraine attacks, drew attention to a possible inhibition of pro-inflammatory neuropeptide release from trigeminal afferents. An isolated preparation of fluid-filled rat skull cavities was used to study effects of NSAIDs and 5-HT(1B/D) agonists on the dura stimulated by inflammatory mediators (bradykinin, histamine and serotonin, 10(-5)M each). The release of immunoreactive CGRP (iCGRP) and immunoreactive PGE(2) (iPGE(2)) was measured in 5-min samples of superfusates using enzyme immunoassays. S(+)-flurbiprofen (10(-6)M) strongly reduced the basal and stimulated iCGRP release and abolished iPGE(2) release; R(-)-flurbiprofen showed much less effect on iPGE(2) liberation and did not influence iCGRP release. The 5-HT(1B/D) agonists naratriptan and CP93,129 were ineffective on both iCGRP and iPGE(2) release. Inspite of its weak COX blocking effect, R(-)-flurbiprofen is reported to exert antinociceptive effects, although it has not been tested in migraine. Only the potent COX blocker S(+)-flurbiprofen also suppressed iCGRP release while the 5-HT(1B/D) agonists were ineffective. Thus, inhibition of meningeal neuropeptide secretion is not a common action principle of the drugs that could be essential for their antimigraine effects.
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PMID:S+ -flurbiprofen but not 5-HT1 agonists suppress basal and stimulated CGRP and PGE2 release from isolated rat dura mater. 1279 37


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