Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1987, an intoxication by cultured mussels produced neurological problems, such as headache, confusion, and loss of memory, particularly severe at times. Neuronal damage was found in the hippocampus and amygdala of four patients. The intoxication was attributed to the presence in mussels of domoic acid, a rare excitatory amino acid acting at the non-NMDA receptor. We now report that a domoic acid-containing mussel extract is more neurotoxic for cultured neurons than purified domoic acid. Moreover, we show that this increase in neurotoxicity is selectively due to domoic acid potentiation of the excitotoxic effect of glutamic acid and aspartic acid present in high concentrations in mussel tissue. We also show that subtoxic concentrations of domoic acid are sufficient to potentiate glutamic acid and aspartic acid neurotoxicity, and we present evidence suggesting that the neurotoxic synergism may occur through a reduction of the voltage-dependent Mg2+ block at the NMDA receptor-associated channel, following activation of non-NMDA receptors by domoic acid. Thus, based on our results, we suggest that the contemporary presence in the brain of concentrations of domoic acid insufficient alone to be toxic, together with excitatory amino acids, of endogenous and eventually of diet-related origin, may have been relevant in the occurrence of the neurological problems reported.
 ...
PMID:Domoic acid-containing toxic mussels produce neurotoxicity in neuronal cultures through a synergism between excitatory amino acids. 135 95

A 26-year-old woman presented with headaches, incoordination and a cerebellar mass (1982). The CT scan revealed dilated ventricles and a hypodense space-occupying lesion adjacent to the fourth ventricle. Neuronal loss, gliosis and masses of Rosenthal fibers were seen in biopsy. There was no evidence of neoplasm. A second biopsy 2 years later was similar to the original specimen. A diagnosis of Alexander's disease was suggested. Later that year the patient's 11-year-old brother manifested a clinical picture initially diagnosed as brainstem glioma, but whose biopsy was characteristic of Alexander's disease. There has been a gradual deterioration of these siblings over the past 6 years (1986-1991). No evidence of neoplasm has appeared.
 ...
PMID:Biopsy diagnosis of familial Alexander's disease. 145 72

Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate-limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2-like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage-specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy).
 ...
PMID:Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. 913 Jun 63

Patients with primary headache syndromes often describe a distribution of pain that involves both frontal and occipital parts of the head. Such a distribution of pain does not respect the cutaneous sensory innervation of the head which would divide it into anterior (trigeminally innervated) and posterior (spinal nerve root innervated) regions. Studies of pain-producing intracranial structures, such as the superior sagittal sinus, have demonstrated that second order neurons as caudal as C2 are activated after either electrical or mechanical stimulation. For this study cats were anaesthetised with halothane (during surgery) and alpha-chloralose (60 mg/kg, i.p., then 20 mg/kg intravenous maintenance), paralysed (gallamine 6 mg/kg) and ventilated. The greater occipital nerve was isolated bilaterally and stimulated unilaterally using hook electrodes with stimuli of 100 V at 0.3 Hz. Metabolic activity in the caudal brain stem and upper cervical cord was measured using 2-deoxyglucose autoradiography and quantitative densitometry. Stimulation of the greater occipital nerve increased metabolic activity by 220% ipsilateral to stimulation and by a lesser amount contralaterally. Increases in metabolic activity were seen in the dorsal horn at the level of C1 and C2 as might be predicted from the cervical origin of the nerve. Neuronal activation appeared contiguous with the trigeminal nucleus caudalis and was in the same distribution as is seen when trigeminally-innervated structures are stimulated. These data suggest that the well recognised clinical phenomenon of pain at the front and back of the head and in the upper neck are likely to be a consequence of overlap of processing of nociceptive information at the level of the second order neurons.
 ...
PMID:Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat. 941 53

Although acetylsalicylic acid (ASA) is one of the most commonly administered drugs in the treatment of acute headaches, the sites of its action and the mechanisms of its therapeutic efficacy are still unclear. In this study using extracellular recording we examined the effects of ASA on spontaneous and mechanically evoked activities of neurons within the medullary dorsal horn with input from the parietal dura mater in rat. Their dural receptive fields were identified by von Frey filaments and found to be mainly located at the medial meningeal artery. All units showed spontaneous activity and had convergent input from the face. Neuronal activities were recorded before and after intravenously applied ASA (30 mg/kg) in 13 and saline in four units. Systemic application of ASA inhibited spontaneous and mechanically evoked activity within 15 min after application. Additionally, neuronal activities were recorded before, during and after topical application of ASA (1 mg/ml) onto the parietal dura mater in 5 units. Topically applied ASA inhibited the mechanically evoked activity, whereas the spontaneous activity remained unchanged. It is concluded, that there are different effects of systemic and topical ASA on trigeminal neuronal activity, which may be due to both central and peripheral mechanisms.
 ...
PMID:Acetylsalicylic acid inhibits meningeal nociception in rat. 1035 88

Within the last 2 decades there has been an explosion in new information on mechanisms underlying pain. Unfortunately this information has not resulted in a similar improvement of our handling of patients with chronic pain including chronic musculoskeletal pain. Neuronal hyperexcitability, which apparently is a key phenomenon in many (if not all) types of chronic pain results in changes in the nervous system from the level of the peripheral nociceptor to the highest cortical centers in the brain. The neuronal plastic changes in chronic pain conditions makes the nociceptive system amenable for treatment with several traditional as well as nontraditional types of interventions. Two treatment areas that seem worth exploring within chronic pain including headache concerns preventive measures and endogenous pain modulation.
Cephalalgia 2001 Sep
PMID:Recent advances in pain research: implications for chronic headache. 1159 9

Nitric oxide (NO) donors such as glyceryl trinitrate cause headache, which suggests involvement of NO in trigeminovascular sensory processing. Sensory transmission at first-order synapses is believed to involve glutamate and the question arises as to whether it is also involved in trigeminovascular sensation and whether it might interact with nitrergic mechanisms. We investigated these questions at the first central synapse in the trigeminovascular sensory system of the cat. Neuronal action potentials in the trigeminal nucleus were recorded while the superior sagittal sinus (SSS) or facial receptive field (RF) were stimulated electrically. Drugs, including the neuronal excitant glutamate, were applied to neurons via microiontophoresis. Results were obtained from 152 neurons activated with A-delta latencies by SSS stimulation and by glutamate. The NO donor S-nitrosoglutathione (SNOG, 50 nA) was applied iontophoretically to 41 neurons during SSS stimulation and 13 neurons during pulsatile glutamate ejection. Responses to both modes of stimulation were enhanced by SNOG; the proportion of neurons enhanced was 56% to SSS stimulation and 59% to glutamate. The inhibitor of nitric oxide synthase (NOS), N(omega)-propyl-L-arginine (p-ARG, 50 nA) was applied iontophoretically to 17 neurons during stimulation of SSS and to 10 neurons during pulsatile glutamate ejection. Responses to both stimuli were suppressed by p-ARG: The proportion of neurons suppressed were: to SSS stimulation 59% and to glutamate 80%. Microiontophoretic ejection of eletriptan (50 nA) reversibly suppressed responses of neurons to SSS stimulation, to RF electrical stimulation and to pulsatile iontophoretic application of glutamate. This suppression of responses was antagonised by the concurrent local iontophoretic application of the 5-HT1B/1D receptor antagonist GR127935 or by concurrent iontophoretic application of the selective 5-HT1D receptor antagonist BRL155732. These results suggest that glutamatergic mechanisms are important in sensory transmission in the trigeminovascular system and that they can be modulated by nitrergic and serotonergic mechanisms.
 ...
PMID:Nitrergic and glutamatergic neuronal mechanisms at the trigeminovascular first-order synapse. 1516 37

Retigabine [D23129; N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamic acid ethyl ester] is an antiepileptic drug with a recently described novel mechanism of action that involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels. These channels (primarily K(V)7.2/7.3) enable generation of the M-current, a subthreshold K(+) current that serves to stabilize the membrane potential and control neuronal excitability. In this regard, retigabine has been shown to have a broad-spectrum of activity in animal models of electrically-induced (amygdala-kindling, maximal electroshock) and chemically-induced (pentylenetetrazole, picrotoxin, NMDA) epileptic seizures. These encouraging results suggest that retigabine may also prove useful in the treatment of other diseases associated with neuronal hyperexcitability. Neuropathic pain conditions are characterized by pathological changes in sensory pathways, which favor action potential generation and enhanced pain transmission. Although sometimes difficult to treat with conventional analgesics, antiepileptics can relieve some symptoms of neuropathic pain. A number of recent studies have reported that retigabine can relieve pain-like behaviors (hyperalgesia and allodynia) in animal models of neuropathic pain. Neuronal activation within several key structures within the CNS can also be observed in various animal models of anxiety. Moreover, amygdala-kindled rats, which have a lowered threshold for neuronal activation, also display enhanced anxiety-like responses. Retigabine dose-dependently reduces unconditioned anxiety-like behaviors when assessed in the mouse marble burying test and zero maze. Early clinical studies have indicated that retigabine is rapidly absorbed and distributed, and is resistant to first pass metabolism. Tolerability is good in humans when titrated up to its therapeutic dose range (600-1200 mg/day). No tolerance, dependence or withdrawal potential has been reported, although adverse effects can include mild dizziness, headache, nausea and somnolence. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.
 ...
PMID:Retigabine: chemical synthesis to clinical application. 1586 50

Microrecordings of three neurons were obtained at the target site in three patients with trigeminal autonomic cephalalgias who were implanted with deep brain stimulators in the posterior hypothalamus. Two patients had chronic cluster headache, one short unilateral neuralgiform headache with conjunctival injection and tearing. Average firing rate was around 24 spikes/s. All neurons were firing randomly, and for most of the recordings in tonic fashion. In one patient, tactile stimulation of the ophthalmic branch, contralateral to the recording site, decreased the firing rate. Neuronal activity in these patients was similar to that reported in animal studies of the posterior hypothalamus. Positioning deep brain stimulators in the posterior hypothalamus may offer a tool to better characterise the activity of this part of the brain in humans.
 ...
PMID:Spontaneous neuronal activity of the posterior hypothalamus in trigeminal autonomic cephalalgias. 1746 72

The near-vision triad, or complex, consists of convergence, miosis, and accommodation. Neuronal pathways that control each of these components are distinct but interrelated. Abnormalities affecting 1 or more components of the complex may present as eye pain, headache, blurred vision, or diplopia at near fixation. Although isolated abnormalities in any one of the components are common, a severe and concurrent defect in all three is rare.(1,2) We describe an 11-year-old child who presented with complete paralysis of the near triad without identifiable neurological defect. The child benefited from prism and plus lenses. To our knowledge, only three previous reports have described patients with idiopathic paralysis of convergence and accommodation in healthy children.(2-4) The methods we used to objectively confirm defects in the near-vision complex and rule out a psychogenic etiology may be instructive to other clinicians.
 ...
PMID:Paralysis of the near-vision triad in a child. 1908 45


1 2 Next >>