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Sample records for intranasal trigeminal sensitivity

  1. Intranasal trigeminal function in subjects with and without an intact sense of smell.

    Science.gov (United States)

    Iannilli, E; Gerber, J; Frasnelli, J; Hummel, T

    2007-03-30

    The intranasal trigeminal system is involved in the perception of odors. To investigate the cerebral processing of sensory information from the trigeminal nerve in detail we studied subjects with and without olfactory function using functional magnetic resonance imaging. A normosmic group (n=12) was compared with a group of anosmic subjects (n=11). For trigeminal stimulation gaseous CO(2) was used. Following right-sided stimulation with CO(2) controls exhibited a stronger right-sided cerebral activation than anosmic subjects. Stronger activation was found in controls compared to anosmic subjects for the right prefrontal cortex, the right somatosensory cortex (SI), and the left parietal insula. In contrast, relatively higher activation was found in anosmic subjects for the left supplementary motor area in the frontal lobe, the right superior and middle temporal lobe, the left parahippocampal gyrus in the limbic lobe, and the sub-lobar region of the left putamen and right insula which was mostly due to a decreased BOLD signal of controls in these areas. Additional conjunction analysis revealed that activated areas common to the two groups were the cerebellum and the right premotor frontal cortex. These data suggest that the processing of the trigeminally mediated information is different in the presence or absence of an intact sense of smell, pointing towards the intimate connection between the two chemosensory systems.

  2. Botulinum neurotoxin type-A when utilized in animals with trigeminal sensitization induced a antinociceptive effect

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    Elcio J Piovesan

    2016-06-01

    Full Text Available ABSTRACT Purpose of the study was evaluate the possible antinociceptive effect of botulinum neurotoxin type-A (BoNT/A in an experimental model of trigeminal neuralgia. Method Neuropathic pain was induced by surgical constriction of the infraorbital nerve in rats. A control group underwent a sham procedure consisting of surgical exposure of the nerve. Subgroups of each group received either BoNT/A or isotonic saline solution. The clinical response was assessed with the -20°C test. Animals that underwent nerve constriction developed sensitization; the sham group did not. Results The sensitization was reversed by BoNT/A treatment evident 24 hours following application. Pronociceptive effect was observed in the sham group following BoNT/A. Conclusion BoNT/A has an antinociceptive effect in sensitized animals and a pronociceptive effect in non-sensitized animals.

  3. Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye.

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    Rahman, Mostafeezur; Okamoto, Keiichiro; Thompson, Randall; Katagiri, Ayano; Bereiter, David A

    2015-05-01

    Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, whereas OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline-evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared with controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline-evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation.

  4. Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

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    Cady Ryan J

    2011-12-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP, a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD. Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.

  5. Frequent mild head injury promotes trigeminal sensitivity concomitant with microglial proliferation, astrocytosis, and increased neuropeptide levels in the trigeminal pain system.

    Science.gov (United States)

    Tyburski, Ashley L; Cheng, Lan; Assari, Soroush; Darvish, Kurosh; Elliott, Melanie B

    2017-12-01

    Frequent mild head injuries or concussion along with the presence of headache may contribute to the persistence of concussion symptoms. In this study, the acute effects of recovery between mild head injuries and the frequency of injuries on a headache behavior, trigeminal allodynia, was assessed using von Frey testing up to one week after injury, while histopathological changes in the trigeminal pain pathway were evaluated using western blot, ELISA and immunohistochemistry.  RESULTS: A decreased recovery time combined with an increased mild closed head injury (CHI) frequency results in reduced trigeminal allodynia thresholds compared to controls. The repetitive CHI group with the highest injury frequency showed the greatest reduction in trigeminal thresholds along with greatest increased levels of calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis. Repetitive CHI resulted in astrogliosis in the central trigeminal system, increased GFAP protein levels in the sensory barrel cortex, and an increased number of microglia cells in the trigeminal nucleus caudalis. Headache behavior in rats is dependent on the injury frequency and recovery interval between mild head injuries. A worsening of headache behavior after repetitive mild head injuries was concomitant with increases in CGRP levels, the presence of astrocytosis, and microglia proliferation in the central trigeminal pathway. Signaling between neurons and proliferating microglia in the trigeminal pain system may contribute to the initiation of acute headache after concussion or other traumatic brain injuries.

  6. Trigeminal Neuralgia

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    ... your doctor. Causes In trigeminal neuralgia, also called tic douloureux, the trigeminal nerve's function is disrupted. Usually, ... logo are trademarks of Mayo Foundation for Medical Education and Research. © 1998-2018 Mayo Foundation for Medical ...

  7. Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons

    NARCIS (Netherlands)

    Rochlin, M William; O'Connor, R.; Giger, Roman J; Verhaagen, J; Farbman, A I

    2000-01-01

    Geniculate (gustatory) and trigeminal (somatosensory) afferents take different routes to the tongue during rat embryonic development. To learn more about the mechanisms controlling neurite outgrowth and axon guidance, we are studying the roles of diffusible factors. We previously profiled the in

  8. Trigeminal neuralgia

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Di Stefano, Giulia; Bendtsen, Lars

    2017-01-01

    -occupying lesion affecting the trigeminal nerve. Differential diagnosis and treatment Important differential diagnoses include trigeminal autonomic cephalalgias, posttraumatic or postherpetic pain and other facial pains. First line treatment is prophylactic medication with sodium channel blockers, and second line......Introduction Trigeminal neuralgia (TN) is characterized by touch-evoked unilateral brief shock-like paroxysmal pain in one or more divisions of the trigeminal nerve. In addition to the paroxysmal pain, some patients also have continuous pain. TN is divided into classical TN (CTN) and secondary TN...

  9. Post-operative orofacial pain, temporomandibular dysfunction and trigeminal sensitivity after recent pterional craniotomy: preliminary study.

    Science.gov (United States)

    Brazoloto, Thiago Medina; de Siqueira, Silvia Regina Dowgan Tesseroli; Rocha-Filho, Pedro Augusto Sampaio; Figueiredo, Eberval Gadelha; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu Tesseroli

    2017-05-01

    Surgical trauma at the temporalis muscle is a potential cause of post-craniotomy headache and temporomandibular disorders (TMD). The aim of this study was to evaluate the prevalence of pain, masticatory dysfunction and trigeminal somatosensory abnormalities in patients who acquired aneurysms following pterional craniotomy. Fifteen patients were evaluated before and after the surgical procedure by a trained dentist. The evaluation consisted of the (1) research diagnostic criteria for TMD, (2) a standardized orofacial pain questionnaire and (3) a systematic protocol for quantitative sensory testing (QST) for the trigeminal nerve. After pterional craniotomy, 80% of the subjects, 12 patients, developed orofacial pain triggered by mandibular function. The pain intensity was measured by using the visual analog scale (VAS), and the mean pain intensity was 3.7. The prevalence of masticatory dysfunction was 86.7%, and there was a significant reduction of the maximum mouth opening. The sensory evaluation showed tactile and thermal hypoesthesia in the area of pterional access in all patients. There was a high frequency of temporomandibular dysfunction, postoperative orofacial pain and trigeminal sensory abnormalities. These findings can help to understand several abnormalities that can contribute to postoperative headache or orofacial pain complaints after pterional surgeries.

  10. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory.

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    Krug, Rosemarie; Benedict, Christian; Born, Jan; Hallschmid, Manfred

    2010-12-01

    We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women. Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone. In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71±0.6 kg/m2; age, 57.61±1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle. Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured. Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44±0.63 yr), i.e. insulin administration did not affect food intake (P>0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (Pwomen do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.

  11. Intravenous dextromethorphan/quinidine inhibits activity of dura-sensitive spinal trigeminal neurons in rats.

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    Sokolov, A Y; Lyubashina, O A; Berkovich, R R; Panteleev, S S

    2015-09-01

    Migraine is a chronic neurological disorder characterized by episodes of throbbing headaches. Practically all medications currently used in migraine prophylaxis have a number of substantial disadvantages and use limitations. Therefore, the further search for principally new prophylactic antimigraine agents remains an important task. The objective of our study was to evaluate the effects of a fixed combination of dextromethorphan hydrobromide and quinidine sulphate (DM/Q) on activity of the spinal trigeminal neurons in an electrophysiological model of trigemino-durovascular nociception. The study was performed in 15 male Wistar rats, which were anaesthetized with urethane/α-chloralose and paralysed using pipecuronium bromide. The effects of cumulative intravenous infusions of DM/Q (three steps performed 30 min apart, 15/7.5 mg/kg of DM/Q in 0.5 mL of isotonic saline per step) on ongoing and dural electrical stimulation-induced neuronal activities were tested in a group of eight rats over 90 min. Other seven animals received cumulative infusion of equal volumes of saline and served as control. Cumulative administration of DM/Q produced steady suppression of both the ongoing activity of the spinal trigeminal neurons and their responses to electrical stimulation of the dura mater. It is evident that the observed DM/Q-induced suppression of trigeminal neuron excitability can lead to a reduction in nociceptive transmission from meninges to higher centres of the brain. Since the same mechanism is believed to underlie the pharmacodynamics of many well-known antimigraine drugs, results of the present study enable us to anticipate the potential efficacy of DM/Q in migraine. © 2014 European Pain Federation - EFIC®

  12. Weather/temperature-sensitive vasomotor rhinitis may be refractory to intranasal corticosteroid treatment.

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    Jacobs, Robert; Lieberman, Philip; Kent, Edward; Silvey, MaryJane; Locantore, Nicholas; Philpot, Edward E

    2009-01-01

    Vasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions. A recently introduced INS with established efficacy in allergic rhinitis and enhanced affinity, fluticasone furoate, may possess the potency and safety profile required to treat chronic VMR(w/t). Two replicate studies (FFR30006 and FFR30007) were conducted in six countries to evaluate the efficacy and safety of fluticasone furoate nasal spray in subjects with VMR(w/t). After a 7- to 14-day screening period, subjects (n = 699) with symptomatic VMR(w/t) received fluticasone furoate, 110 mug q.d. or placebo for 4 weeks in these two randomized, double-blind, parallel-group studies. Subjects rated their nasal symptoms (congestion, rhinorrhea, and postnasal drip) twice daily on a 4-point categorical scale and evaluated their overall response to treatment at study end. Fluticasone furoate did not significantly improve daily reflective total nasal symptom scores, the primary end point, versus placebo (p = 0.259) and there was no improvement in any other measure of efficacy. The active treatment was well tolerated. Fluticasone furoate was not effective in treating subjects with a newly defined condition, weather-sensitive VMR. These unexpected results suggest that VMR(w/t) is a distinct subgroup of VMR that is refractory to treatment with INSs. Additional study of other treatments for VMR(w/t) (including INSs) is warranted.

  13. Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome.

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    Derkach, K V; Ivantsov, A O; Chistyakova, O V; Sukhov, I B; Buzanakov, D M; Kulikova, A A; Shpakov, A O

    2017-06-01

    We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

  14. Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery.

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    Wu, Youbin; Wu, Shipo; Hou, Lihua; Wei, Wei; Zhou, Meng; Su, Zhiguo; Wu, Jie; Chen, Wei; Ma, Guanghui

    2012-08-01

    A novel thermal sensitive hydrogel was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). A serial of hydrogels containing different amount of GP and HTCC with diverse quarternize degree (QD, 41%, 59%, 79.5%, and 99%) were prepared and characterized by rheological method. The hydrogel was subsequently evaluated for intranasal vaccine delivery with adenovirus based Zaire Ebola virus glycoprotein antigen (Ad-GPZ). Results showed that moderate quarternized HTCC (60% and 79.5%) hydrogel/antigen formulations induced highest IgG, IgG1, and IgG2a antibody titers in serum, as well as mucosal IgA responses in lung wash, which may attributed to the prolonged antigen residence time due to the thermal-sensitivity of this hydrogel. Furthermore, CD8(+) splenocytes for IFN-γ positive cell assay and the release profile of Th1/Th2 type cytokines (IFN-γ, IL-2, IL-10, and IL-4) showed that hydrogel/Ad-GPZ generated an overwhelmingly enhanced Th1 biased cellular immune response. In addition, this hydrogel displayed low toxicity to nasal tissue and epithelial cells even by frequently intranasal dosing of hydrogel. All these results strongly supported this hydrogel as a safe and effective delivery system for nasal immunization. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  15. Olfactory dysfunction affects thresholds to trigeminal chemosensory sensations.

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    Frasnelli, J; Schuster, B; Hummel, T

    2010-01-14

    Next to olfaction and gustation, the trigeminal system represents a third chemosensory system. These senses are interconnected; a loss of olfactory function also leads to a reduced sensitivity in the trigeminal chemosensory system. However, most studies so far focused on comparing trigeminal sensitivity to suprathreshold stimuli; much less data is available with regard to trigeminal sensitivity in the perithreshold range. Therefore we assessed detection thresholds for CO(2), a relatively pure trigeminal stimulus in controls and in patients with olfactory dysfunction (OD). We could show that OD patients exhibit higher detection thresholds than controls. In addition, we were able to explore the effects of different etiologies of smell loss on trigeminal detection thresholds. We could show that in younger subjects, patients suffering from olfactory loss due to head trauma are more severely impaired with regard to their trigeminal sensitivity than patients with isolated congenital anosmia. In older patients, we could not observe any differences between different etiologies, probably due to the well known age-related decrease of trigeminal sensitivity. Furthermore we could show that a betterment of the OD was accompanied by decreased thresholds. This was most evident in patients with postviral OD. In conclusion, factors such as age, olfactory status and etiology of olfactory disorder can affect responsiveness to perithreshold trigeminal chemosensory stimuli. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  16. IMAGING EVALUATION OF TRIGEMINAL NEURALGIA

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    Marinos KONTZIALIS

    2017-12-01

    Full Text Available Trigeminal neuralgia is a debilitating pain syndrome in the sensory distribution of the trigeminal nerve. Compression of the cisternal segment of the trigeminal nerve by a vessel, usually an artery, is considered the most common cause of trigeminal neuralgia. A number of additional lesions may affect the trigeminal nerve anywhere along its course from the trigeminal nuclei to the most peripheral branches to cause facial pain. Relevant differential considerations are reviewed starting proximally at the level of the brainstem.

  17. Perception of trigeminal mixtures.

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    Filiou, Renée-Pier; Lepore, Franco; Bryant, Bruce; Lundström, Johan N; Frasnelli, Johannes

    2015-01-01

    The trigeminal system is a chemical sense allowing for the perception of chemosensory information in our environment. However, contrary to smell and taste, we lack a thorough understanding of the trigeminal processing of mixtures. We, therefore, investigated trigeminal perception using mixtures of 3 relatively receptor-specific agonists together with one control odor in different proportions to determine basic perceptual dimensions of trigeminal perception. We found that 4 main dimensions were linked to trigeminal perception: sensations of intensity, warmth, coldness, and pain. We subsequently investigated perception of binary mixtures of trigeminal stimuli by means of these 4 perceptual dimensions using different concentrations of a cooling stimulus (eucalyptol) mixed with a stimulus that evokes warmth perception (cinnamaldehyde). To determine if sensory interactions are mainly of central or peripheral origin, we presented stimuli in a physical "mixture" or as a "combination" presented separately to individual nostrils. Results showed that mixtures generally yielded higher ratings than combinations on the trigeminal dimensions "intensity," "warm," and "painful," whereas combinations yielded higher ratings than mixtures on the trigeminal dimension "cold." These results suggest dimension-specific interactions in the perception of trigeminal mixtures, which may be explained by particular interactions that may take place on peripheral or central levels. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Imaging the trigeminal nerve

    International Nuclear Information System (INIS)

    Borges, Alexandra; Casselman, Jan

    2010-01-01

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  19. Imaging the trigeminal nerve

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    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093, Lisboa (Portugal)], E-mail: borgalexandra@gmail.com; Casselman, Jan [Department of Radiology, A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals (Belgium)

    2010-05-15

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  20. Expression and function of a CP339,818-sensitive K+ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

    Science.gov (United States)

    Sforna, Luigi; D'Adamo, Maria Cristina; Servettini, Ilenio; Guglielmi, Luca; Pessia, Mauro; Franciolini, Fabio

    2015-01-01

    Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current (IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation (IDRKs). PMID:25652918

  1. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

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    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  2. Trigeminal trophic syndrome

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    Parimalam Kumar

    2014-01-01

    Full Text Available Trigeminal trophic syndrome (TTS is a rare cause of facial ulceration, consequent to damage to the trigeminal nerve or its central sensory connections. We reporta case of TTS in a 48-year-old woman with Bell′s palsy following herpes zoster infection. The patient was treated and counseled. There hasnot been any recurrence for 1 year and the patient is being followed-up. The diagnosis of TTS should be suspected when there is unilateral facial ulceration, especially involving the ala nasi associated with sensory impairment.

  3. Triggering trigeminal neuralgia

    DEFF Research Database (Denmark)

    Di Stefano, Giulia; Maarbjerg, Stine; Nurmikko, Turo

    2018-01-01

    Introduction Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification...

  4. Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis

    Directory of Open Access Journals (Sweden)

    Durham Paul L

    2010-12-01

    Full Text Available Abstract Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization.

  5. Bioavailability of intranasal metoclopramide.

    OpenAIRE

    Ward, M J; Buss, D C; Ellershaw, J; Nash, A; Routledge, P A

    1989-01-01

    After intranasal administration of metoclopramide, (5 mg in 0.5 ml sterile water) the maximum plasma concentration of 13.5 +/- 7.3 (mean +/- s.d.) ng ml-1 was achieved. Absolute bioavailability was 50.5 +/- 29.5%, 110 +/- 41 min later. We conclude that the intranasal route does not allow rapid absorption of the drug and is not associated with greater bioavailability than the oral route.

  6. MR imaging of trigeminal neuropathy

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    Kim, Si Yeon; Yoon, Pyeong Ho; Chung, Jin Il; Lee, Seung Ik; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-03-01

    The trigeminal nerve is the largest of the cranial nerves and has both sensory and motor functions. It can be divided into proximal (brainstem, preganglionic, gasserian ganglion, and cavernous sinus) and distal (extracranial opthalmic, maxillary, and mandibular) segments. Patients with trigeminal neuropathy present with a wide variety of symptoms, and lesions producing those symptoms may occur anywhere along the protracted course of the trigeminal nerve, from its distal facial branches to its nuclear columns in the brainstem. The purpose of this article is to illustrate the normal anatomy of the trigeminal nerve and associated various pathologic conditions. These are arranged anatomically according to their site of interaction with it.

  7. MRI EVALUATION OF TRIGEMINAL NEURALGIA

    Directory of Open Access Journals (Sweden)

    Sama Surya Sravani

    2017-04-01

    Full Text Available BACKGROUND Neuralgia is the set of symptoms associated with nerve dysfunction. The most common of these symptoms is pain, which can occur intermittently in one area of the body or can radiate along the length of a damaged nerve. The most common type of neuralgia is trigeminal neuralgia. This study focuses on the effectiveness of MRI in visualising the entire course of trigeminal nerve and to diagnose the exact location, aetiology responsible for trigeminal neuralgia and possible pretreatment evaluation. MATERIALS AND METHODS Clinical records and imaging studies of 30 patients between the ages of 18-60 years who presented to the Department of Radiodiagnosis, KIMS, for brain magnetic resonance imaging with (Philips 1.5T machine during June 2015 to December 2016 were analysed retrospectively. RESULTS  The entire course of trigeminal nerve is evaluated in these patients.  There are different causes of trigeminal neuralgia, but in our study, most frequent cause is mechanical irritation of nerve is due to neurovascular contact (24 cases. The other causes identified are cerebellopontine angle lesions, brainstem tumours, demyelinating disease involving brainstem.  The cisternal portion of the nerve is the most common site of involvement. CONCLUSION Trigeminal nerve is the largest cranial nerve. MRI is unique as it produces images of entire course of the nerve. Of the many causes of trigeminal neuralgia, neurovascular conflict is the most common cause. The exact location and degree of neurovascular compression is graded on MRI.

  8. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  9. Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine

    Directory of Open Access Journals (Sweden)

    Jordan L. Hawkins

    2017-12-01

    Conclusion:. Our findings demonstrate that nVNS inhibits mechanical nociception and represses expression of proteins associated with peripheral and central sensitization of trigeminal neurons in a novel rodent model of episodic migraine.

  10. Botulinum toxin in trigeminal neuralgia.

    Science.gov (United States)

    Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia

    2017-01-06

    Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Trigeminal Nerve Root Demyelination Not Seen in Six Horses Diagnosed with Trigeminal-Mediated Headshaking

    Directory of Open Access Journals (Sweden)

    Veronica L. Roberts

    2017-05-01

    Full Text Available Trigeminal-mediated headshaking is an idiopathic neuropathic facial pain syndrome in horses. There are clinical similarities to trigeminal neuralgia, a neuropathic facial pain syndrome in man, which is usually caused by demyelination of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. Our hypothesis was that the neuropathological substrate of headshaking in horses is similar to that of trigeminal neuralgia in man. Trigeminal nerves, nerve roots, ganglia, infraorbital, and caudal nasal nerves from horse abattoir specimens and from horses euthanized due to trigeminal-mediated headshaking were removed, fixed, and processed for histological assessment by a veterinary pathologist and a neuropathologist with particular experience of trigeminal neuralgia histology. No histological differences were detected between samples from horses with headshaking and those from normal horses. These results suggest that trigeminal-mediated headshaking may have a different pathological substrate from trigeminal neuralgia in man.

  12. Anatomy of the trigeminal nerve

    NARCIS (Netherlands)

    van Eijden, T.M.G.J.; Langenbach, G.E.J.; Baart, J.A.; Brand, H.S.

    2017-01-01

    The trigeminal nerve is the fifth cranial nerve (n. V), which plays an important role in the innervation of the head and neck area, together with other cranial and spinal nerves. Knowledge of the nerve’s anatomy is very important for the correct application of local anaesthetics.

  13. Gamma knife radiosurgery for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Tomida, Mihoko; Hayashi, Motohiro; Kawakami, Yoriko; Ishimaru, Jun-ichi

    2009-01-01

    Gamma knife surgery (GKS) has been employed for treating intractable pain such as trigeminal neuralgia (TN) and pain relief has been gained from the treatment, however, little is understood about the side effects of other sensitivities induced from GKS. We assessed ten patients (four men and six women; mean age 67 years) with TN who were investigated by questionnaire for symptoms and visual analog scale (VAS) of pain, and their threshold of touch sensation was examined using Semmes-Weinstein monofilaments, cold sensation and allodynia before and after GKS. MR and CT images were obtained after a Leksell head frame was applied to the head parallel to the trigeminal nerve. These images were uploaded to a computer system and retro-Gasserian area planned the target was correctly marked on the images of a computer in which gamma planning software was installed. All patients were irradiated with a maximum dose of 90 Gy at retro-Gasserian using a 4 mm collimator. The mean±standard deviation (SD) of VAS of pain was 8.5±1.3 and 8 patients had facial paresthesia before GKS. All patients experienced a significant reduction in pain without side effects such as effect on the peripheral nerves without 6 month after GKS. Allodynia, facial paresthesia or cold sensation numbness occurred in the patients before GKS disappeared according to complete pain relief. These results suggest that GKS is a safe and effective treatment for TN. (author)

  14. CT of intranasal pleomorphic adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Clark, M.; Fatterpekar, G.M.; Mukherji, S.K.; Buenting, J. [Department of Radiology, 3324 Infirmary CB F 7510, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7510 (United States)

    1999-08-01

    Intranasal pleomorphic adenoma is rare. We report the CT features this tumor in a 41-year-old woman who presented to us with right nasal obstruction and a 2-day history of epistaxis. (orig.) With 3 figs., 9 refs.

  15. Straightening the trigeminal nerve axis by complete dissection of arachnoidal adhesion and its neuroendoscopic confirmation for trigeminal neuralgia without neurovascular compression

    Directory of Open Access Journals (Sweden)

    Mami Ishikawa, MD, PhD

    2017-12-01

    Conclusions: Straightening the trigeminal nerve axis by complete dissection of the arachnoidal adhesion around the trigeminal nerve was effective for typical trigeminal neuralgia without neurovascular compression.

  16. MR findings of trigeminal neurinoma

    International Nuclear Information System (INIS)

    Park, Hong Suk; Han, Moon Hee; Chang, Kee Hyun; Yoo, In Kyu; Kim, Sam Soo; Lee, Kyoung Won; Jung, Hee Won; Yeon, Kyung Mo

    1997-01-01

    To describe the MRI findings of trigeminal neurinoma. We retrospectively analyzed the MRI findings of 19 patients with trigeminal neurinomas proven by surgery and pathologic examination. Axial T1- and T2-weighted MR images in all patients and gadolinium-enhanced T1-weighted images in 14 patients were obtained at 2.0T(8 cases), 1.5T(6 cases) or 0.5T(5 cases). These were analyzed in terms of tumor size, signal intensity, degree of contrast enhancement, the presence or absence of cystic change and denervation atrophy of the masticator muscles. Clinical manifestations included sensory abnormality or pain(n=12), headache(n=10), impaired visual acuity or diplopia(n=6), hearing loss or tinnitus(n=3), weakness of masticator muscles(n=2), and mass or nasal obstruction(n=2). On MR images, tumor size was seen to average 4.2(range 1.5-6)cm;tumors were located in the posterior cranial fossa(n=8), middle cranial fossa(n=4), ophthalmic nerve(n=2), maxillary nerve(n=1), and mandibular nerve(n=1), and in three cases were dumbbell-shaped and extended into both the middle and posterior cranial fossa. On T1-weighted images, signals were isointense with cortical grey matter, in ten cases(53%), and of low intensity in nine (47%);on T2-weighted images, signals were of high intensity in 15cases(79%) and were isointense in four (21%). Cystic change was seen in 12 cases(63%). After enhancement, all (14/14) the tumors enhanced. Denervation atrophy was seen in nine cases(47%) and all of these involved the trigeminal ganglion or mandibular nerve. A trigeminal neurinoma shows similar signal intensity and enhancement to other cranial neurinomas with a higher incidence of cystic degeneration. Its location and shape are characteristic, and where there is involvement of the trigeminal ganglion or mandibular nerve, denervation atrophy may be seen

  17. MR findings of trigeminal neurinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hong Suk; Han, Moon Hee; Chang, Kee Hyun; Yoo, In Kyu; Kim, Sam Soo; Lee, Kyoung Won; Jung, Hee Won; Yeon, Kyung Mo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-08-01

    To describe the MRI findings of trigeminal neurinoma. We retrospectively analyzed the MRI findings of 19 patients with trigeminal neurinomas proven by surgery and pathologic examination. Axial T1- and T2-weighted MR images in all patients and gadolinium-enhanced T1-weighted images in 14 patients were obtained at 2.0T(8 cases), 1.5T(6 cases) or 0.5T(5 cases). These were analyzed in terms of tumor size, signal intensity, degree of contrast enhancement, the presence or absence of cystic change and denervation atrophy of the masticator muscles. Clinical manifestations included sensory abnormality or pain(n=12), headache(n=10), impaired visual acuity or diplopia(n=6), hearing loss or tinnitus(n=3), weakness of masticator muscles(n=2), and mass or nasal obstruction(n=2). On MR images, tumor size was seen to average 4.2(range 1.5-6)cm;tumors were located in the posterior cranial fossa(n=8), middle cranial fossa(n=4), ophthalmic nerve(n=2), maxillary nerve(n=1), and mandibular nerve(n=1), and in three cases were dumbbell-shaped and extended into both the middle and posterior cranial fossa. On T1-weighted images, signals were isointense with cortical grey matter, in ten cases(53%), and of low intensity in nine (47%);on T2-weighted images, signals were of high intensity in 15cases(79%) and were isointense in four (21%). Cystic change was seen in 12 cases(63%). After enhancement, all (14/14) the tumors enhanced. Denervation atrophy was seen in nine cases(47%) and all of these involved the trigeminal ganglion or mandibular nerve. A trigeminal neurinoma shows similar signal intensity and enhancement to other cranial neurinomas with a higher incidence of cystic degeneration. Its location and shape are characteristic, and where there is involvement of the trigeminal ganglion or mandibular nerve, denervation atrophy may be seen.

  18. Trigeminal Neuropathy in Sjogren′s Syndrome

    Directory of Open Access Journals (Sweden)

    Pinheiro L

    1999-01-01

    Full Text Available Trigeminal neuropathy is the most common CNS disorder in Sjogren′s syndrome. It is believed to be caused by vasculitis. Unless this is recognised, a diagnosis of trigeminal neuralgia is often made. The therapeutic response to steroids is unpredictable. There are two subgroups - those with associated collagen disorders and those only with the sicca syndrome.

  19. Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain.

    Science.gov (United States)

    Shelukhina, Irina; Mikhailov, Nikita; Abushik, Polina; Nurullin, Leniz; Nikolsky, Evgeny E; Giniatullin, Rashid

    2017-01-01

    Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown. Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons. Both ACh and carbachol significantly increased nociceptive firing in peripheral terminals of meningeal trigeminal nerves recorded by local suction electrode. Strong nociceptive firing was also induced by nicotine, implying essential role of nicotinic AChRs in control of excitability of trigeminal nerve endings. Nociceptive firing induced by carbachol was reduced by muscarinic antagonist atropine, whereas the action of nicotine was prevented by the nicotinic blocker d-tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but not nicotine induced massive degranulation of meningeal mast cells known to release multiple pro-nociceptive mediators. Enzymes terminating ACh action, acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change the firing per se but induced nociceptive activity, sensitive to d-tubocurarine, after pretreatment of meninges with the migraine mediator CGRP. This observation suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine and carbachol induced intracellular Ca 2+ transients in trigeminal neurons partially overlapping with expression of capsaicin-sensitive TRPV1 receptors. Trigeminal nerve terminals in meninges, as well as dural mast cells and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic and muscarinic AChRs, which

  20. Intranasal sedatives in pediatric dentistry

    Science.gov (United States)

    AlSarheed, Maha A.

    2016-01-01

    Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry. Results: Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its’ onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Conclusion: Intranasal midazolam, ketamine and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine and sufentanil have proven to be effective premedications. PMID:27570849

  1. Trigeminal neuralgia: report of 3 cases

    International Nuclear Information System (INIS)

    Park, Geum Mee; Ki, Joo Yeon; Cho, Bong Hae; Nah, Kyung Soo

    2002-01-01

    Orofacial pain can be caused by intracranial disorders or can be musculoskeletal, vascular, internal derangemental, and neurologic in origin. The neurologic pain is derived from structural and functional disorders of nerve, and the trigeminal neuralgia is the typical manifestation. Trigeminal neuralgia is known from centuries ago, and is one of the most common pains in human. We present our experience with three patients who have trigeminal neuralgia. The first case is a 50-year-old female who had no specific evidence radiographically. Second is a 50-year-old male with microvascular compression on right trigeminal nerve. The third case is a 60-year-old female who had a neoplasm in cerebellopontine angle with associated mass effect.

  2. Trigeminal neuralgia: report of 3 cases

    Energy Technology Data Exchange (ETDEWEB)

    Park, Geum Mee; Ki, Joo Yeon; Cho, Bong Hae; Nah, Kyung Soo [College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    2002-03-15

    Orofacial pain can be caused by intracranial disorders or can be musculoskeletal, vascular, internal derangemental, and neurologic in origin. The neurologic pain is derived from structural and functional disorders of nerve, and the trigeminal neuralgia is the typical manifestation. Trigeminal neuralgia is known from centuries ago, and is one of the most common pains in human. We present our experience with three patients who have trigeminal neuralgia. The first case is a 50-year-old female who had no specific evidence radiographically. Second is a 50-year-old male with microvascular compression on right trigeminal nerve. The third case is a 60-year-old female who had a neoplasm in cerebellopontine angle with associated mass effect.

  3. Stereotactic Radiosurgery for Classical Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Henry Kodrat

    2016-04-01

    Full Text Available Trigeminal neuralgia is a debilitating pain syndrome with a distinct symptom mainly excruciating facial pain that tends to come and go unpredictably in sudden shock-like attacks. Medical management remains the primary treatment for classical trigeminal neuralgia. When medical therapy failed, surgery with microvascular decompression can be performed. Radiosurgery can be offered for classical trigeminal neuralgia patients who are not surgical candidate or surgery refusal and they should not in acute pain condition. Radiosurgery is widely used because of good therapeutic result and low complication rate. Weakness of this technique is a latency period, which is time required for pain relief. It usually ranges from 1 to 2 months. This review enlightens the important role of radiosurgery in the treatment of classical trigeminal neuralgia.

  4. Microvascular decompression for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Khan, S.A.; Khan, B.; Khan, A.A.; Afridi, E.A.A.; Mehmood, S.; Muhammad, G.; Hussain, I.; Zadran, K.K.; Bhatti, S.N.

    2015-01-01

    Background: Trigeminal Neuralgia (TGN) is the most frequently diagnosed type of facial pain. In idiopathic type of TGN it is caused by the neuro-vascular conflict involving trigeminal nerve. Microvascular decompression (MVD) aims at addressing this basic pathology in the idiopathic type of TGN. This study was conducted to determine the outcome and complications of patients with idiopathic TGN undergoing MVD. Method: In a descriptive case series patients with idiopathic TGN undergoing MVD were included in consecutive manner. Patients were diagnosed on the basis of detailed history and clinical examination. Retromastoid approach with craniectomy was used to access cerebellopontine angle (CP-angle) and microsurgical decompression was done. Patients were followed up for 6 months. Results: A total of 53 patients underwent MVD with mean age of 51.6±4.2 years and male predominance. In majority of cases (58.4 percentage) both Maxillary and Mandibular divisions were involved. Per-operatively superior cerebellar artery (SCA) was causing the neuro-vascular conflict in 33 (62.2 percentage) of the cases, anterior inferior cerebellar artery (AICA) in 6 (11.3 percentage) cases, both CSA and AICA in 3 (5.6 percentage) cases, venous compressions in only 1 (1.8percentage) patient and thick arachnoid adhesions were seen in 10 (18.9 percentage) patients. Postoperatively, 33 (68 percentage) patients were pain free, in 14 (26.45 percentage) patients pain was significantly improved whereas in 3 (5.6 percentage) patients there was mild improvement in symptoms. Three (5.6 percentage) patients did not improve after the primary surgery. Cerebrospinal fluid (CSF) leak was encountered in 7 (13.2 percentage) patients post-operatively, 4 (7.5 percentage) patients developed wound infection and 1 (1.8 percentage) patient developed aseptic meningitis. Three (5.6 percentage) patients had transient VII nerve palsy while one patient developed permanent VII nerve palsy. Conclusion: MVD is a safe and

  5. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  6. Trigeminal induced arousals during human sleep.

    Science.gov (United States)

    Heiser, Clemens; Baja, Jan; Lenz, Franziska; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A

    2015-05-01

    Arousals caused by external stimuli during human sleep have been studied for most of the sensorial systems. It could be shown that a pure nasal trigeminal stimulus leads to arousals during sleep. The frequency of arousals increases dependent on the stimulus concentration. The aim of the study was to evaluate the influence of different stimulus durations on arousal frequency during different sleep stages. Ten young healthy volunteers with 20 nights of polysomnography were included in the study. Pure trigeminal stimulation with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages to the volunteers using an olfactometer. The application was performed during different sleep stages (light sleep, deep sleep, REM sleep). The number of arousals increased with rising stimulus duration and stimulus concentration during each sleep stage. Trigeminal stimuli during sleep led to arousals in dose- and time-dependent manner.

  7. Cilostazol induces C-fos expression in the trigeminal nucleus caudalis and behavioural changes suggestive of headache with the migraine-like feature photophobia in female rats

    DEFF Research Database (Denmark)

    Christensen, S L; Petersen, Steffen; Sørensen, Dorte B

    2018-01-01

    -like behaviours and c-fos expression in rats. In order to evaluate the predictive validity of the model, we examined the response to the migraine specific drug sumatriptan. Methods The effect of cilostazol (125 mg/kg p.o.) in female Sprague Dawley rats was evaluated on a range of spontaneous behavioural...... parameters, light sensitivity and mechanical sensitivity thresholds. We also measured c-fos expression in the trigeminal nucleus caudalis. Results Cilostazol increased light sensitivity and grooming behaviour. These manifestations were not inhibited by sumatriptan. Cilostazol also induced c-fos expression...... in the trigeminal nucleus caudalis. Furthermore, trigeminal - but not hind paw hyperalgesia was observed. Conclusion The altered behaviours are suggestive of cilostazol induced headache with migraine-like features, but not specific. The presence of head specific hyperalgesia and the c-fos response in the trigeminal...

  8. MR imaging of persistent primitive trigeminal artery

    International Nuclear Information System (INIS)

    Ashikaga, Ryuichiro; Araki, Yutaka; Ono, Yukihiko; Ishida, Osamu; Mabuchi, Nobuhisa.

    1997-01-01

    The persistent trigeminal artery is the most common anomaly of the primitive carotid-vertebrobasilar anastomoses. We reviewed MR images and MR angiographies of 11 patients with primitive trigeminal artery. In 8 of the 11 cases, PTA were identified with conventional long TR spin-echo images. In 8 of 11 cases, a hypoplastic basilar trunk associated with PTA was seen on both MR images and MR angiographies. In 7 of 11 cases, a hypoplasia or agenesis of the ipsilateral posterior communicating artery was seen on MR angiographies. (author)

  9. Small-fiber dysfunction in trigeminal neuralgia

    DEFF Research Database (Denmark)

    Cruccu, G.; Leandri, M.; Iannetti, G. D.

    2001-01-01

    Background: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information...... was significantly longer than that of the age-matched controls. The nonpainful-side latency correlated significantly with the carbamazepine dose. Conclusions: LEP detect severe impairment of the nociceptive afferent system on the painful side of patients with idiopathic as well as symptomatic trigeminal neuralgia...

  10. MRI analysis of vascular compressive trigeminal neuralgia

    International Nuclear Information System (INIS)

    Tang Ling; Chai Weimin; Song Qi; Ling Huawei; Miao Fei; Chen Kemin

    2006-01-01

    Objective: To analyze the offending vessels of vascular compressive trigeminal neuralgia by magnetic resonance tomographic angiography (MRTA). Methods: MRTA images of 235 asymptomatic trigeminal nerves and 147 symptomatic trigeminal nerves were analyzed by two radiologists who were blinded to the clinical findings. Judgment was made on if there were some vessels close to the trigeminal nerve. The diameter of the offending vessel, the distance from the offending vessel's contact point to the pons and the direction of the vessel toward the nerve were also recorded at the same time. Group t-test and Chi-Square test were used for statistics. Results: Two hundred and forty-two trigeminal nerves of all 382 nerves can be detected offending vessels on MRTA images, 111 of 242 trigeminal nerves were asymptomatic, the rest 131 were symptomatic. Statistical analysis indicated that the distance from the offending vessel's contact point to the pons in symptomatic group (the median is 2 mm) was shorter than that in the asymptomatic group (the median is 4 mm) (P<0.01). In 89.3% cases (117/131) of the symptomatic group the angle between the vessel and the nerve is larger than 45 degree, but only in 67.6% cases (75/111) in the asymptomatic group the angle is larger than 45 degree. That means significant difference is between the two groups (P<0.01). Vessel-nerve compression can be seen in 1 case of asymptomatic group (0.4%, 1/235) and 45 eases in symptomatic group (30.6%, 45/147). The vessel-nerve compression rate of the symptomatic group was much higher than that of the asymptomatic group (P<0.01). Conclusion: MR is a useful tool to evaluate the offending vessels of vascular compressive trigeminal neuralgia. The distance from the offending vessel's contact point to the pons and the direction of the vessel toward the nerve are related to the onset of vascular compressive trigeminal neuralgia. (authors)

  11. Trigeminal perineural spread of renal cell carcinoma

    International Nuclear Information System (INIS)

    Hornik, Alejandro; Rosenblum, Jordan; Biller, Jose

    2012-01-01

    A 55-year-old man had a five-day history of “pins and needles” sensation on the left chin. Examination showed decreased pinprick sensation on the territory of the left mandibular branch of the trigeminal nerve. Brain magnetic resonance imaging (MRI) with gadolinium showed enhancement involving the left mandibular branch. Computed tomography (CT) of the chest, abdomen, and pelvis showed a left kidney mass diagnosed as renal carcinoma following nephrectomy. The “numb-chin” syndrome heralds or accompanies systemic malignancies. Trigeminal perineural spread has been well-documented in head and neck neoplasms, however, to our knowledge, it has not been reported in renal neoplasms. (author)

  12. Structural magnetic resonance imaging can identify trigeminal system abnormalities in classical trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Danielle DeSouza

    2016-10-01

    Full Text Available Classical trigeminal neuralgia (TN is a chronic pain disorder that has been described as one ofthe most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN.

  13. Ganglioglioma of the trigeminal nerve: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Athale, S.; Jinkins, J.R. [Neuroradiology Section, The University of Texas Health Science Center at San Antonio, 7703 F. Curl Drive, San Antonio, TX 78284-7800 (United States); Hallet, K.K. [Neuropathology Department, The University of Texas Health Science Center at San Antonio, Texas (United States)

    1999-08-01

    Ganglioglioma of the cranial nerves is extremely rare; only a few cases involving the optic nerves have been reported. We present a case of ganglioglioma of the trigeminal nerve, which was isointense with the brain stem on all MRI sequences and showed no contrast enhancement. (orig.) With 2 figs., 6 refs.

  14. Idiopathic trigeminal neuropathy in a poodle

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Aparicio

    2010-12-01

    Full Text Available A seven years old, male poodle is examined presenting acute mandible paralysis (dropped jaw, drooling and difficulty for the apprehension and chewing; not evidence of an other alteration of cranial nerves. The muscular biopsy rules out a myositisof masticatory muscles. The disorder is resolved completely in 3 weeks confirming diagnosis of idiopathic trigeminal neuropathy.

  15. Management of trigeminal neuralgia by radiofrequency ...

    African Journals Online (AJOL)

    The outcome depends on the type of TN with best results with classical idiopathic type. Also better results occurred with isolated V3 affection. The radiofrequency thermocoagulation of trigeminal nerve is a low risk, highly effective and minimally invasive procedure that should be started with in all cases of TN.

  16. Management of Trigeminal Neuralgia using Amitriptyline and ...

    African Journals Online (AJOL)

    Trigeminal neuralgia (TN) is a clinical condition presenting with severe, paroxysmal facial pain, often described by patients also known as tic douloureux. Carbamazepine (CBZ) is the drug of choice, but some patients develop adverse effects and some others may become unresponsive to CBZ. We present three cases of TN ...

  17. Inclusion of Cocoa as a Dietary Supplement Represses Expression of Inflammatory Proteins in Spinal Trigeminal Nucleus in Response to Chronic Trigeminal Nerve Stimulation

    Science.gov (United States)

    Cady, Ryan J.; Denson, Jennifer E.; Durham, Paul L.

    2013-01-01

    Scope Central sensitization is implicated in the pathology of temporomandibular joint disorder (TMD) and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves. Methods and results Male Sprague Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund’s adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of GLAST and MKP-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3, P-p38, GFAP, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression. Conclusion Based on our findings, we speculate that cocoa enriched diets could be beneficial as a natural therapeutic option for TMD and other chronic orofacial pain conditions. PMID:23576361

  18. Somesthetic, gustatory, olfactory function and salivary flow in patients with neuropathic trigeminal pain.

    Science.gov (United States)

    Siviero, M; Teixeira, M J; de Siqueira, J T T; Siqueira, S R D T

    2010-07-01

    To determine somesthetic, olfactory, gustative and salivary abnormalities in patients with burning mouth syndrome (BMS), idiopathic trigeminal neuralgia (ITN) and trigeminal postherpetic neuralgia (PHN). Twenty patients from each group (BMS, ITN, PHN) and 60 healthy controls were evaluated with a systematized quantitative approach of thermal (cold and warm), mechanical, pain, gustation, olfaction and salivary flow; data were analyzed with ANOVA, Tukey, Kruskal-Wallis and Dunn tests with a level of significance of 5%. There were no salivary differences among the groups with matched ages; the cold perception was abnormal only at the mandibular branch of PHN (P = 0.001) and warm was abnormal in all trigeminal branches of PHN and BMS; mechanical sensitivity was altered at the mandibular branch of PHN and in all trigeminal branches of BMS. The salty, sweet and olfactory thresholds were higher in all studied groups; the sour threshold was lower and there were no differences of bitter. All groups showed abnormal thresholds of gustation and olfaction; somesthetic findings were discrete in ITN and more common in PHN and BMS; central mechanisms of balance of sensorial inputs might be underlying these observations.

  19. Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

    Science.gov (United States)

    Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

    2018-01-01

    Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect of the gamma knife treatment on the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

    Science.gov (United States)

    Song, Zhi-Xiu; Qian, Wei; Wu, Yu-Quan; Sun, Fang-Jie; Fei, Jun; Huang, Run-Sheng; Fang, Jing-Yu; Wu, Cai-Zhen; An, You-Ming; Wang, Daxin; Yang, Jun

    2014-01-01

    To understand the mechanism of the gamma knife treating the trigeminal neuralgia. Using the MASEP-SRRS type gamma knife treatment system, 140 Chinese patients with trigeminal neuralgia (NT) were treated in our hospital from 2002 to 2010, in which the pain relief rate reached 95% and recurrence rate was 3% only. We investigated the effect of the gamma knife treatment on the trigeminal nerve root in 20 Chinese patients with primary trigeminal neuralgia by the magnetic resonance imager (MRI) observation. 1) The cross-sectional area of trigeminal nerve root became smaller and MRI signals were lower in the treatment side than those in the non-treatment side after the gamma knife treatment of primary trigeminal neuralgia; 2) in the treatment side, the cross-sectional area of the trigeminal nerve root decreased significantly after the gamma knife treatment; 3) there was good correlation between the clinical improvement and the MRI findings; and 4) the straight distance between the trigeminal nerve root and the brainstem did not change after the gamma knife treatment. The pain relief induced the gamma knife radiosurgery might be related with the atrophy of the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

  1. Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

    Science.gov (United States)

    Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

    2018-03-14

    The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

  2. Trigeminal Trophic Syndrome – Case Report

    Directory of Open Access Journals (Sweden)

    Boštjan Matos

    2015-05-01

    Full Text Available 1024x768 Trigeminal trophic syndrome is a rare condition resulting from compulsive self-manipulation of the skin after a peripheral or central injury to the trigeminal system. The classic triad consists of trigeminal anesthesia, facial paresthesias, and crescentric lateral nasal alar erosion and ulceration. Although the symptoms are visibly clear, the diagnosis is not easy to establish. The appearance of the ulcers mimics many other disease entities such as neoplasm, infection, granulomatous disease, vasculitis and factitial dermatitis. Trigeminal trophic syndrome should be considered with a positive neurologic history and when laboratory and biopsy workup is inconclusive. Once diagnosis is confirmed, treatment is complicated and often multidisciplinary. We report a case of a woman who developed a strictly unilateral crescent ulcer of the ala nasi after resection of an statoacoustic neurinoma. A clinician who is faced with a patient with nasal ulceration should consider this diagnosis.     Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  3. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...

  4. INTRANASAL DEXMEDETOMIDINE VS. INTRANASAL MIDAZOLAM FOR PREMEDICATION OF PAEDIATRIC SURGERY PATIENTS

    Directory of Open Access Journals (Sweden)

    Revi N

    2016-06-01

    Full Text Available AIM Preoperative anxiety is one of the most common problems faced by anyone practising paediatric anaesthesia. Various drugs have been used in various routes to get a calm but cooperative child before induction of anaesthesia. Midazolam and dexmedetomidine have already proved their value in paediatric premedication. This study was conducted to compare the effects of these two drugs given intranasally. MATERIALS AND METHODS 100 children falling under the inclusion criteria were assigned to groups of 50 each. They received either intranasal midazolam 0.2 mg/kg (group M or intranasal dexmedetomidine 2 mcg/kg (Group D as premedication. They were compared with regards to the sedation status, anxiety levels and cardiovascular status every 10 minutes, at parental separation and at face mask application. RESULTS The mean sedation score obtained at all-time intervals, at parental separation and more importantly at mask induction were much lower for the midazolam group compared to the dexmedetomidine group. The mean anxiety levels, in general, were lower in the midazolam group, but they attained statistical significance only at 10 minutes and at mask induction. The heart rate measured up to 20 minutes after drug administration did not show much difference between both groups, but at 30 minutes, 40 minutes and at parental separation, heart rate was found to be lower in the dexmedetomidine group. CONCLUSION Intranasal dexmedetomidine and intranasal midazolam are equally effective in providing satisfactory parental separation, but intranasal midazolam produced superior conditions for mask acceptance than intranasal dexmedetomidine.

  5. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  6. Intranasal tumors in dogs: diagnosis and treatment

    International Nuclear Information System (INIS)

    Theisen, S.K.; Lewis, D.D.; Hosgood, G.

    1996-01-01

    Intranasal tumors are rare in dogs and occur mostly in middle-aged and old dogs. The malignant behavior of these tumors is reflected more by their tendency to invade local tissue than by a tendency to produce distant metastasis. Distant metastasis may, however, become more important as success in treatment of the initial lesion improves. The history and clinical signs (sneezing, nasal discharge, and facial deformity) of intranasal tumor in dogs often reflect intranasal disease but are usually nonspecific. Diagnostics should include at least the minimum data base, high-detail radiographs of the nasal cavity obtained while the dog is anesthetized, and biopsy of nasal cavity tissue. Radiotherapy with or without aggressive cytoreduction is the only treatment that significantly extends survival of these dogs. Ortho-voltage, megavoltage, or brachytherapy (implantation of (192)lridium) has been used

  7. Pharmaceutical management of trigeminal neuralgia in the elderly

    NARCIS (Netherlands)

    Oomens, M.A.E.M.; Forouzanfar, T.

    2015-01-01

    Classical trigeminal neuralgia (CTN) is a severe neuropathic pain in the distribution of one or more branches of the trigeminal nerve, which occurs in recurrent episodes, causing deterioration in quality of life, affecting everyday habits and inducing severe disability. The aim of this review is to

  8. Pharmaceutical Management of Trigeminal Neuralgia in the Elderly

    NARCIS (Netherlands)

    Oomens, M.A.E.; Forouzanfar, T.

    2015-01-01

    Classical trigeminal neuralgia (CTN) is a severe neuropathic pain in the distribution of one or more branches of the trigeminal nerve, which occurs in recurrent episodes, causing deterioration in quality of life, affecting everyday habits and inducing severe disability. The aim of this review is to

  9. Trigeminal small-fibre dysfunction in patients with diabetes mellitus

    DEFF Research Database (Denmark)

    Agostino, R.; Cruccu, G.; Iannetti, G. D.

    2000-01-01

    Objective: To investigate trigeminal small-fibre function in patients with diabetes mellitus. Methods: In 52 diabetic patients we studied the trigeminal laser evoked potentials after stimulation of the skin bordering the lower lip. In the 21 patients with the severest peripheral nerve damage we a...

  10. Trigeminal neuralgia: how often are trigeminal nerve-vessel contacts found by MRI in normal volunteers

    International Nuclear Information System (INIS)

    Kress, B.; Schindler, M.; Haehnel, S.; Sartor, K.; Rasche, D.; Tronnier, V.

    2006-01-01

    Purpose: To assess prospectively how often contacts are found between the trigeminal nerve and arteries or veins in the perimesencephalic cistern via MRI in normal volunteers. Materials and methods: 48 volunteers without a history of trigeminal neuralgia were examined prospectively (MRI at 1.5T; T2-CISS sequence, coronal orientation, 0.9 mm slice thickness). Two radiologists decided by consensus whether there was a nerve-vessel contact in the perimesencephalic cistern. Results: In 27% of the volunteers, no contact was found between the trigeminal nerve and regional vessels, while in 73%, such a contact was present. In 61% of the cases, the offending vessel was an artery, in 39%, it was a vein. In 2 volunteers, a deformation of the nerve was noted. Conclusion: Contrary to what has been suggested by retrospective studies, the majority of normal volunteers, if studied prospectively, do show a contact between the trigeminal nerve and local vessels. A close proximity between the nerve and regional vessels is thus normal and is not necessarily proof of a pathological nerve-vessel conflict. (orig.)

  11. A Case of Acoustic Shock with Post-trauma Trigeminal-Autonomic Activation

    Directory of Open Access Journals (Sweden)

    Alain Londero

    2017-08-01

    Full Text Available This study reports the case of an acoustic shock injury (ASI, which did not result in a significant hearing loss, but was followed by manifold chronic symptoms both within (tinnitus, otalgia, tingling in the ear, tension in the ear, and red tympanum and outside the ears (blocked nose, pain in the neck/temporal region. We suggest that these symptoms may result from a loop involving injury to middle ear muscles, peripheral inflammatory processes, activation and sensitization of the trigeminal nerve, the autonomic nervous system, and central feedbacks. The pathophysiology of this ASI is reminiscent of that observed in post-traumatic trigeminal-autonomic cephalalgia. This framework opens new and promising perspectives on the understanding and medical management of ASI.

  12. Linear accelerator radiosurgery for trigeminal neuralgia: case report

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hyong Geun [Dongguk University International Hospital, Goyang (Korea, Republic of)

    2006-06-15

    Trigeminal neuralgia is defined as an episodic electrical shock-like sensation in a dermatomal distribution of the trigeminal nerve. When medications fail to control pain, various procedures are used to attempt to control refractory pain. Of available procedures, stereotactic radiosurgery is the least invasive procedure and has been demonstrated to produce significant pain relief with minimal side effects. Recently, linear accelerators were introduced as a tool for radiosurgery of trigeminal neuralgia beneath the already accepted gamma unit. Author have experienced one case with trigeminal neuralgia treated with linear accelerator. The patient was treated with 85 Gy by means of 5 mm collimator directed to trigeminal nerve root entry zone. The patient obtained pain free without medication at 20 days after the procedure and remain pain free at 6 months after the procedure. He didn't experience facial numbness or other side effects.

  13. SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

    Science.gov (United States)

    Gulbransen, Brian; Silver, Wayne; Finger, Tom

    2008-01-01

    Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260

  14. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    International Nuclear Information System (INIS)

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-01-01

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80–90). The mean retreatment dose was 84.4 Gy (range, 60–90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  15. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  16. Comparison of Trigeminal and Postherpetic Neuralgia

    Directory of Open Access Journals (Sweden)

    C Peter N Watson

    1996-01-01

    Full Text Available Although postherpetic neuralgia and trigeminal neuralgia (tic douloureux are common causes of facial pain, they have very little in common aside from lancinating pain (other qualities of pain in each disorder are different. Each disorder affects different areas of the face and the treatment of each is quite dissimilar. The pathogenesis of these two disorders quite likely involves different mechanisms. This report reviews aspects of these two difficult pain problems, particularly with reference to the work of the late Gerhard Fromm, to whom this is dedicated.

  17. Comparison of dexmedetomidine versus midazolam for intranasal ...

    African Journals Online (AJOL)

    route; however, it is not as painful as the intramuscular route, and it is absorbed directly ... respiratory tract infection, any central nervous system disorder, refusal for intranasal administration or history of allergic reaction to dexmedetomidine ... and the calculated dose of drug diluted to a total volume of 1 ml was administered ...

  18. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Directory of Open Access Journals (Sweden)

    Balaji Kannan

    2011-01-01

    Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

  19. The usual treatment of trigeminal autonomic cephalalgias.

    Science.gov (United States)

    Pareja, Juan A; Álvarez, Mónica

    2013-10-01

    Trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, and rhinorrhea (SUNCT). Conventional pharmacological therapy can be successful in the majority of trigeminal autonomic cephalalgias patients. Most cluster headache attacks respond to 100% oxygen inhalation, or 6 mg subcutaneous sumatriptan. Nasal spray of sumatriptan (20 mg) or zolmitriptan (5 mg) are recommended as second choice. The bouts can be brought under control by a short course of corticosteroids (oral prednisone: 60-100 mg/day, or intravenous methylprednisolone: 250-500 mg/day, for 5 days, followed by tapering off the dosage), or by long-term prophylaxis with verapamil (at least 240 mg/day). Alternative long-term preventive medications include lithium carbonate (800-1600 mg/day), methylergonovine (0.4-1.2 mg/day), and topiramate (100-200 mg/day). As a rule, paroxysmal hemicrania responds to preventive treatment with indomethacin (75-150 mg/day). A short course of intravenous lidocaine (1-4 mg/kg/hour) can reduce the flow of attacks during exacerbations of SUNCT. Lamotrigine (100-300 mg/day) is the preventive drug of choice for SUNCT. Gabapentin (800-2700 mg/day), topiramate (50-300 mg/day), and carbamazepine (200-1600 mg/day) may be of help. © 2013 American Headache Society.

  20. CT findings of trigeminal neurinoma (root type)

    International Nuclear Information System (INIS)

    Munemoto, Shigeru; Ishiguro, Shuzo; Kimura, Akira; Shoin, Katsuo; Futami, Kazuya; Rikimaru, Shigeho; Shimizu, Hiroshi; Inoue, Kazuhiko

    1986-01-01

    The CT findings of three patients with trigeminal neurinomas arising from the trigeminal nerve roots were analysed. The tumors were seated behind the posterior wall of the petrous bone: The tumors showed a low density, an isodensity, or a mixed iso and low density on the CT scan. After contrast infusion, the two tumors were markedly enhanced, and the last showed rim enhancement. All the tumors had cystic lesions. None of the tumors had surrounding brain edema. In the 1st case, the tumor compressed the cerebellum mainly; in the 2nd case, it compressed the brain stem, and in the last case, it compressed both the brain stem and the cerebellum. The 2nd case is easy to differentiate from the acoustic neurinoma by its location. The other two cases could be differentiated from the acoustic neurinoma by means of CECT, because the enhanced masses were attached to the apex of the petrous bone. Metrizamide CT cisternography played an important role in circumscribing the tumor. (author)

  1. Chemosensory Information Processing between Keratinocytes and Trigeminal Neurons

    Science.gov (United States)

    Sondersorg, Anna Christina; Busse, Daniela; Kyereme, Jessica; Rothermel, Markus; Neufang, Gitta; Gisselmann, Günter; Hatt, Hanns; Conrad, Heike

    2014-01-01

    Trigeminal fibers terminate within the facial mucosa and skin and transmit tactile, proprioceptive, chemical, and nociceptive sensations. Trigeminal sensations can arise from the direct stimulation of intraepithelial free nerve endings or indirectly through information transmission from adjacent cells at the peripheral innervation area. For mechanical and thermal cues, communication processes between skin cells and somatosensory neurons have already been suggested. High concentrations of most odors typically provoke trigeminal sensations in vivo but surprisingly fail to activate trigeminal neuron monocultures. This fact favors the hypothesis that epithelial cells may participate in chemodetection and subsequently transmit signals to neighboring trigeminal fibers. Keratinocytes, the major cell type of the epidermis, express various receptors that enable reactions to multiple environmental stimuli. Here, using a co-culture approach, we show for the first time that exposure to the odorant chemicals induces a chemical communication between human HaCaT keratinocytes and mouse trigeminal neurons. Moreover, a supernatant analysis of stimulated keratinocytes and subsequent blocking experiments with pyrodoxalphosphate-6-azophenyl-2′,4′-disulfonate revealed that ATP serves as the mediating transmitter molecule released from skin cells after odor stimulation. We show that the ATP release resulting from Javanol® stimulation of keratinocytes was mediated by pannexins. Consequently, keratinocytes act as chemosensors linking the environment and the trigeminal system via ATP signaling. PMID:24790106

  2. Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Warissara Rongthong

    2017-05-01

    Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

  3. Trigeminal neuralgia secondary to basilar impression: A case report

    Directory of Open Access Journals (Sweden)

    Maurus Marques de Almeida Holanda

    2015-01-01

    Full Text Available We report a rare case of trigeminal neuralgia. A 23-year-old woman with a history of 1 year of typical trigeminal neuralgia manifested the characteristics of basilar impression. Magnetic resonance imaging (MRI demonstrated basilar impression, deformity of the posterior fossa with asymmetry of petrous bone, and compression of medulla oblongata in the topography of the odontoid apophysis. The operation was performed through a suboccipital craniectomy. The neuralgia disappeared after surgery and remains completely resolved until today. This is the second reported case of trigeminal neuralgia in a patient with basilar impression in Brazil.

  4. Linear accelerator stereotactic radiosurgery for trigeminal neuralgia.

    Science.gov (United States)

    Varela-Lema, Leonor; Lopez-Garcia, Marisa; Maceira-Rozas, Maria; Munoz-Garzon, Victor

    2015-01-01

    Stereotactic radiosurgery is accepted as an alternative for patients with refractory trigeminal neuralgia, but existing evidence is fundamentally based on the Gamma Knife, which is a specific device for intracranial neurosurgery, available in few facilities. Over the last decade it has been shown that the use of linear accelerators can achieve similar diagnostic accuracy and equivalent dose distribution. To assess the effectiveness and safety of linear-accelerator stereotactic radiosurgery for the treatment of patients with refractory trigeminal neuralgia. We carried out a systematic search of the literature in the main electronic databases (PubMed, Embase, ISI Web of Knowledge, Cochrane, Biomed Central, IBECS, IME, CRD) and reviewed grey literature. All original studies on the subject published in Spanish, French, English, and Portuguese were eligible for inclusion. The selection and critical assessment was carried out by 2 independent reviewers based on pre-defined criteria. In view of the impossibility of carrying out a pooled analysis, data were analyzed in a qualitative way. Eleven case series were included. In these, satisfactory pain relief (BIN I-IIIb or reduction in pain = 50) was achieved in 75% to 95.7% of the patients treated. The mean time to relief from pain ranged from 8.5 days to 3.8 months. The percentage of patients who presented with recurrences after one year of follow-up ranged from 5% to 28.8%. Facial swelling or hypoesthesia, mostly of a mild-moderate grade appeared in 7.5% - 51.9% of the patients. Complete anaesthesia dolorosa was registered in only study (5.3%). Cases of hearing loss (2.5%), brainstem edema (5.8%), and neurotrophic keratoplasty (3.5%) were also isolated. The results suggest that stereotactic radiosurgery with linear accelerators could constitute an effective and safe therapeutic alternative for drug-resistant trigeminal neuralgia. However, existing studies leave important doubts as to optimal treatment doses or the

  5. Facial injections of pruritogens and algogens excite partly overlapping populations of primary and second-order trigeminal neurons in mice.

    Science.gov (United States)

    Akiyama, T; Carstens, M Iodi; Carstens, E

    2010-11-01

    Intradermal cheek injection of pruitogens or algogens differentially elicits hindlimb scratching or forelimb wiping, suggesting that these behaviors distinguish between itch and pain. We studied whether pruritogens and algogens excite separate or overlapping populations of primary afferent and second-order trigeminal neurons in mice. Calcium imaging of primary sensory trigeminal ganglion (TG) cells showed that 15.4% responded to histamine, 5.8% to the protease-activated receptor (PAR)-2 agonist, 13.4% to allyl isothiocyanate (AITC), and 36.7% to capsaicin. AITC and/or capsaicin activated the vast majority of histamine- and PAR-2 agonist-sensitive TG cells. A chemical search strategy identified second-order neurons in trigeminal subnucleus caudalis (Vc) responsive to histamine, the PAR-2 agonist, or AITC. A minority of histamine or PAR-2 agonist-responsive Vc neurons responded to the other pruritogen, whereas a large majority of puritogen-responsive Vc neurons responded to capsaicin and/or AITC. A minority of AITC-responsive Vc neurons responded to pruritogens, whereas most responded to capsaicin. These data indicate that most primary and higher-order trigeminal sensory neurons are activated by both pruritic and algesic stimuli, although a minority exhibit selectivity. The results are discussed in terms of population codes for itch and pain that result in distinct behavioral responses of hindlimb scratching and forelimb wiping that are mediated at lumbar and cervical segmental levels, respectively.

  6. Gamma Knife® radiosurgery for trigeminal neuralgia.

    Science.gov (United States)

    Yen, Chun-Po; Schlesinger, David; Sheehan, Jason P

    2011-11-01

    Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.

  7. Update on neuropathic pain treatment for trigeminal neuralgia

    Science.gov (United States)

    Al-Quliti, Khalid W.

    2015-01-01

    Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial pain, originating from the trigeminal nerve. Careful history of typical symptoms is crucial for diagnosis. Most cases are caused by vascular compression of the trigeminal root adjacent to the pons leading to focal demyelination and ephaptic axonal transmission. Brain imaging is required to exclude secondary causes. Many medical and surgical treatments are available. Most patients respond well to pharmacotherapy; carbamazepine and oxcarbazepine are first line therapy, while lamotrigine and baclofen are considered second line treatments. Other drugs such as topiramate, levetiracetam, gabapentin, pregabalin, and botulinum toxin-A are alternative treatments. Surgical options are available if medications are no longer effective or tolerated. Microvascular decompression, gamma knife radiosurgery, and percutaneous rhizotomies are most promising surgical alternatives. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on available evidence and guidelines. PMID:25864062

  8. Neurophysiological aspects of the trigeminal sensory system: an update.

    Science.gov (United States)

    Van der Cruyssen, Frederic; Politis, Constantinus

    2018-02-23

    The trigeminal system is one of the most complex cranial nerve systems of the human body. Research on it has vastly grown in recent years and concentrated more and more on molecular mechanisms and pathophysiology, but thorough reviews on this topic are lacking, certainly on the normal physiology of the trigeminal sensory system. Here we review the current literature on neurophysiology of the trigeminal nerve from peripheral receptors up to its central projections toward the somatosensory cortex. We focus on the most recent scientific discoveries and describe historical relevant research to substantiate further. One chapter on new insights of the pathophysiology of pain at the level of the trigeminal system is added. A database search of Medline, Embase and Cochrane was conducted with the search terms 'animal study', 'neurophysiology', 'trigeminal', 'oral' and 'sensory'. Articles were manually selected after reading the abstract and where needed the article. Reference lists also served to include relevant research articles. Fifty-six articles were included after critical appraisal. Physiological aspects on mechanoreceptors, trigeminal afferents, trigeminal ganglion and central projections are reviewed in light of reference works. Embryologic and anatomic insights are cited where needed. A brief description of pathophysiology of pain pathways in the trigeminal area and recent advances in dental stem cell research are also discussed. Neurophysiology at the level of the central nervous system is not reviewed. The current body of knowledge is mainly based on animal and cadaveric studies, but recent advancements in functional imaging and molecular neuroscience are elucidating the pathways and functioning of this mixed nerve system. Extrapolation of animal studies or functioning of peripheral nerves should be warranted.

  9. Transethmoidal intranasal meningoencephalocele in an adult with recurrent meningitis.

    Science.gov (United States)

    Hasegawa, Takafumi; Sugeno, Naoto; Shiga, Yusei; Takeda, Atsushi; Karibe, Hiroshi; Tominaga, Teiji; Itoyama, Yasuto

    2005-08-01

    Intranasal meningoencephalocele is a rarely encountered congenital malformation. We report a case of transethmoidal intranasal meningoencephalocele in a 52-year old man with recurrent purulent meningitis. After treatment of the acute meningitis, frontal craniotomy followed by the removal of the stalk of the meningoencephalocele and repair of the bony defect was successfully performed. He has had no further meningitis or CSF rhinorrhea post-operatively. Detailed neuroradiological examination and appropriate surgical treatment are important to prevent fatal neurological complications of intranasal meningoencephalocele.

  10. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...... subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment...

  11. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    Science.gov (United States)

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  12. Field-testing of the ICHD-3 beta diagnostic criteria for classical trigeminal neuralgia

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Sørensen, Morten Togo; Gozalov, Aydin

    2015-01-01

    INTRODUCTION: We aimed to field-test the beta version of the third edition of the International Classification of Headache Disorders (ICHD-3 beta) diagnostic criteria for classical trigeminal neuralgia (TN). The proposed beta draft of the 11th version of the International Classification of Diseases...... (ICD-11 beta) is almost exclusively based on the ICHD-3 beta classification structure although slightly abbreviated. We compared sensitivity and specificity to ICHD-2 criteria, and evaluated the needs for revision. METHODS: Clinical characteristics were systematically and prospectively collected from...

  13. Deposition of intranasal glucocorticoids--preliminary study.

    Science.gov (United States)

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  14. Trigeminal neuralgia and facial nerve paralysis

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [IPOFG, Department of Radiology, Lisbon (Portugal)

    2005-03-01

    The trigeminal nerve is the largest of the cranial nerves. It provides sensory input from the face and motor innervation to the muscles of mastication. The facial nerve is the cranial nerve with the longest extracranial course, and its main functions include motor innervation to the muscles of facial expression, sensory control of lacrimation and salivation, control of the stapedial reflex and to carry taste sensation from the anterior two-thirds of the tongue. In order to be able adequately to image and follow the course of these cranial nerves and their main branches, a detailed knowledge of neuroanatomy is required. As we are dealing with very small anatomic structures, high resolution dedicated imaging studies are required to pick up normal and pathologic nerves. Whereas CT is best suited to demonstrate bony neurovascular foramina and canals, MRI is preferred to directly visualize the nerve. It is also the single technique able to detect pathologic processes afflicting the nerve without causing considerable expansion such as is usually the case in certain inflammatory/infectious conditions, perineural spread of malignancies and in very small intrinsic tumours. Because a long course from the brainstem nuclei to the peripheral branches is seen, it is useful to subdivide the nerve in several segments and then tailor the imaging modality and the imaging study to that specific segment. This is particularly true in cases where topographic diagnosis can be used to locate a lesion in the course of these nerves. (orig.)

  15. Trigeminal neuralgia and facial nerve paralysis

    International Nuclear Information System (INIS)

    Borges, Alexandra

    2005-01-01

    The trigeminal nerve is the largest of the cranial nerves. It provides sensory input from the face and motor innervation to the muscles of mastication. The facial nerve is the cranial nerve with the longest extracranial course, and its main functions include motor innervation to the muscles of facial expression, sensory control of lacrimation and salivation, control of the stapedial reflex and to carry taste sensation from the anterior two-thirds of the tongue. In order to be able adequately to image and follow the course of these cranial nerves and their main branches, a detailed knowledge of neuroanatomy is required. As we are dealing with very small anatomic structures, high resolution dedicated imaging studies are required to pick up normal and pathologic nerves. Whereas CT is best suited to demonstrate bony neurovascular foramina and canals, MRI is preferred to directly visualize the nerve. It is also the single technique able to detect pathologic processes afflicting the nerve without causing considerable expansion such as is usually the case in certain inflammatory/infectious conditions, perineural spread of malignancies and in very small intrinsic tumours. Because a long course from the brainstem nuclei to the peripheral branches is seen, it is useful to subdivide the nerve in several segments and then tailor the imaging modality and the imaging study to that specific segment. This is particularly true in cases where topographic diagnosis can be used to locate a lesion in the course of these nerves. (orig.)

  16. Trigeminal Trophic Syndrome Associated With the Use of Synthetic Marijuana.

    Science.gov (United States)

    Khan, Fawad A; Manacheril, Rinu; Ulep, Robin; Martin, Julie E; Chimakurthy, Anil

    2017-01-01

    Trigeminal trophic syndrome (TTS) is an uncommon disorder of the trigeminal nerve tract and trigeminal brainstem nucleus. The syndrome is characterized by a triad of unilateral crescentic ulcers with anesthesia and paresthesias of the involved trigeminal dermatomes. A 24-year-old right-handed black female presented to our emergency department with a 4-week history of rapidly progressive painless desquamation/denudation of skin over her right face and scalp. Four weeks prior, she had been admitted to another institution for seizures and was diagnosed with seizures provoked by synthetic marijuana use. She was afebrile during her initial presentation at our institution. Dermatologic examination revealed denudation of the epidermis and partial dermis over the right frontal, parietal, and temporal scalp with associated alopecia. To our knowledge, the association of disorders of the trigeminal nerve pathway, including TTS, with the use of synthetic marijuana has not been previously reported. The long-term neurologic effects of synthetic marijuana are difficult to predict, and the pathologic underpinnings of TTS are largely unknown. Further studies dedicated to exploring the underlying molecular and cellular mechanisms may translate into effective therapies and approaches to halt and reverse the process and prevent tissue destruction and cosmetic disfigurement.

  17. MRI volumetry for the preoperative diagnosis of trigeminal neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Kress, Bodo; Schindler, Markus; Haehnel, Stefan; Sartor, Klaus; Stippich, Christoph [University of Heidelberg, Division of Neuroradiology, Department of Neurology, Medical Center, 69120 Heidelberg (Germany); Rasche, Dirk; Tronnier, Volker [University of Heidelberg, Department of Neurosurgery, Medical Center, 69120 Heidelberg (Germany)

    2005-07-01

    To assess whether quantitative measuring methods can help improve the reliability of MRI-based evaluations of the pathological role of a neurovascular conflict between an artery and the trigeminal nerve. In a prospective study, magnetic resonance images were obtained from 62 patients with unilateral facial pain and 50 healthy test subjects. In coronal T1- and T2-weighted sequences volume measurements were performed by regions of interest and compared intraindividually (healthy versus affected side in the patient populations and right versus left side in the group of test subjects) and on the basis of the different clinical pictures (t test for dependent and independent samples, p<0.05). In patients with trigeminal neuralgia, the affected nerve showed a smaller volume than the trigeminal nerve on the healthy side (p<0.001). Such a volume difference was noted neither in the other patients nor in the healthy test subjects. Quantitative MRI measurements allow a pathological neurovascular conflict to be distinguished from a nonpathological condition where an artery is in close proximity to the trigeminal nerve. The measured volume difference between the healthy and the affected nerve in patients with neuralgia is indicative of trigeminal nerve atrophy resulting from damage to the nerve. (orig.)

  18. Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review.

    Science.gov (United States)

    Kumar, S; Rastogi, S; Kumar, S; Mahendra, P; Bansal, M; Chandra, L

    2013-01-01

    Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve. It is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. Pain attacks start abruptly and last several seconds but may persist 1 to 2 minutes. The attacks are initiated by non painful physical stimulation of specific areas (trigger points or zones) that are located ipsilateral to the pain. After each episode, there is usually a refractive period during which stimulation of the trigger zone will not induce the pain. According to the European Federation of Neurological Societies (EFNS) guidelines on neuropathic pain assessment and the American Academy of Neurology (AAN)-EFNS guidelines on TN management the neurophysiological recording of trigeminal reflexes represents the most useful and reliable test for the neurophysiological diagnosis of trigeminal pains. The present article discusses different techniques for investigation of the trigeminal system by which an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.

  19. Evaluation of trigeminal neurovascular compression in patients with trigeminal neuralgia with 3.0 T MRI

    International Nuclear Information System (INIS)

    Zhang Lirong; Wang Dehang; Wang Dongqing; Wu Min; Xu Guangming; Ma Cong

    2012-01-01

    Objective: To identify anatomical characteristics of neurovascular compression associated with trigeminal neuralgia (TN). Methods: Fifty patients with TN (23 of 50 patients underwent microvascular decompression) and 50 patients without facial pain underwent 3.0 T MRI scanning for analysis of 50 trigeminal nerves ipsilateral to TN symptoms, 50 contralateral to TN symptoms, and 100 in asymptomatic patients. MRI sequences included balanced fast-field echo and 3D MR angiography. Images were fused and reconstructed into virtual cisternoscopy images to determine the degree (severity of compression was defined as follows: 1=no compression; 2 =compressed by a vein; 3 =contacted by an artery; 4 =indented by an artery; and 5 =nerve displaced or distorted by an artery) and site of neurovascular compression (the point of each offending vascular structure: proximal was defined as located in 1/3 length of the cisternal segment of the trigeminal nerve near root entry zone; the place of superior was defined as above the cisternal segment of the trigeminal nerve). Reconstructed MPR images were used to measure nerve length and cross sectional area. The chi-square test was used for all 2 × 2 contingency tables. The t-test was used for dependent samples. The Logistic regression was used for prediction of occurrence of the event of TN. Results: Twenty-three of 50 patients with TN underwent microvascular decompression, which confirmed predicted neurovascular relationships in all cases, and 21 of 23 patients were pain free after the operation. The incidence of neurovascular compression on asymptomatic nerves (no. of level 1=79, level 2=5, level 3 =8, level 4 =8), on nerves contralateral to TN symptoms (no. of level 1=27, level 2 =6, level 3 =9, level 4 =8), and on nerves ipsilateral to TN symptoms (no. of level 1=4, level 2 =12, level 3 =12, level 4 =7, level 5 =15) was 21.0% (21/100), 46.0% (23/50), and 92.0% (46/50), respectively. The difference between symptomatic and asymptomatic

  20. Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

    Directory of Open Access Journals (Sweden)

    Golam Mustafa

    2017-01-01

    Full Text Available Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

  1. Fluticasone furoate: A new intranasal corticosteroid

    Directory of Open Access Journals (Sweden)

    R Kumar

    2012-01-01

    Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

  2. Gamma-knife radiosurgery in the treatment of trigeminal schwannomas

    International Nuclear Information System (INIS)

    Peker, S.; Bayrakli, F.; Kilic, T.; Pamir, M.N.

    2007-01-01

    Trigeminal nerve schwannomas account for 0.07 %-0.28 % of all intracranial tumors. Advances in skull base surgery have led to more aggressive resection of these tumors, but surgery may associated with development of new neurological deficits. In this report, we analyse the long-term results 15 patients with newly diagnosed or residual/recurrent trigeminal schwannoma who underwent gamma-knife treatment. During a mean 61 months of follow-up, MRI revealed reduction of tumor size in 13 and no size change in 2 patients. The tumor growth control rate was 100 % and only 1 patient had transient facial numbness and diplopia. For patients with small to moderate size trigeminal schwannomas, gamma-knife radiosurgery is associated with good tumor control and a minimal risk of adverse radiation effects. (author)

  3. Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery

    International Nuclear Information System (INIS)

    Flickinger, John C.; Kondziolka, Douglas; Lunsford, L. Dade

    1996-01-01

    Purpose and objective: To define the relationships between dose and tumor diameter for the risks of developing trigeminal, facial, and acoustic neuropathies after acoustic neuroma radiosurgery, a large single-institution experience was analyzed. Materials and methods: Two hundred and thirty-eight patients with unilateral acoustic neuromas who underwent Gamma knife radiosurgery between 1987-1994 with 6-91 months of follow-up (median 30 months) were studied. Minimum tumor doses were 12-20 Gy (median 15 Gy). Transverse tumor diameter varied from 0.3-5.5 cm (median 2.1 cm). The relationships of dose and diameter to the development of cranial neuropathies were delineated by multivariate logistic regression. Results: The development of post-radiosurgery neuropathies affecting cranial nerves V, VII, and VIII were correlated with minimum tumor dose and transverse tumor diameter (P min for VIII where P=0.10). A comparison of the dose-diameter response curves showed the acoustic nerve to be the most sensitive to doses of 12-16 Gy and the facial nerve to be the least sensitive. Conclusion: The risks of developing trigeminal, facial, and acoustic neuropathies following acoustic neuroma radiosurgery can be predicted from the transverse tumor diameter and the minimum tumor dose using models constructed from data presently available

  4. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

    Science.gov (United States)

    Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

    2015-09-01

    Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they

  5. Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

    Science.gov (United States)

    Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

    2018-04-01

    To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

  6. Unilateral pure trigeminal motor nerve neuropathy: A rare case report

    Directory of Open Access Journals (Sweden)

    Nishant K Srivastava

    2014-01-01

    Full Text Available Unilateral pure trigeminal motor nerve neuropathy is an extremely rare and unique condition, characterized by atrophy of the muscles, innervated by the motor branch of the trigeminal nerve. We report such a case in a 25-year-old male patient. The diagnosis was made on the basis of clinical and radiological examinations. Magnetic Resonance Imaging (MRI proved to be the key for establishing the diagnosis, which showed atrophy and fatty infiltration over the affected side of the muscles of mastication. We were unable to establish the cause of the condition even after performing a brain MRI.

  7. Trigeminal Neuralgia and Multiple Sclerosis: A Historical Perspective.

    Science.gov (United States)

    Burkholder, David B; Koehler, Peter J; Boes, Christopher J

    2017-09-01

    Trigeminal neuralgia (TN) associated with multiple sclerosis (MS) was first described in Lehrbuch der Nervenkrankheiten für Ärzte und Studirende in 1894 by Hermann Oppenheim, including a pathologic description of trigeminal root entry zone demyelination. Early English-language translations in 1900 and 1904 did not so explicitly state this association compared with the German editions. The 1911 English-language translation described a more direct association. Other later descriptions were clinical with few pathologic reports, often referencing Oppenheim but citing the 1905 German or 1911 English editions of Lehrbuch. This discrepancy in part may be due to the translation differences of the original text.

  8. Significance of neurovascular contact in classical trigeminal neuralgia

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Wolfram, Frauke; Gozalov, Aydin

    2015-01-01

    and degree of neurovascular contact. Severe neurovascular contact was defined as displacement or atrophy of the trigeminal nerve. A total of 135 patients with classical trigeminal neuralgia were included. Average age of disease onset was 53.0 years (95% confidence interval mean 40.5-55.5) and current age...... was 60.1 years (95% % confidence interval mean 57.5-62.7). Eighty-two (61%, 95% confidence interval 52-69%) patients were female. Neurovascular contact was prevalent both on the symptomatic and asymptomatic side [89% versus 78%, P = 0.014, odds ratio = 2.4 (1.2-4.8), P = 0.017], while severe...

  9. ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.

    Science.gov (United States)

    Nakaya, Yuka; Tsuboi, Yoshiyuki; Okada-Ogawa, Akiko; Shinoda, Masamichi; Kubo, Asako; Chen, Jui Yen; Noma, Noboru; Batbold, Dulguun; Imamura, Yoshiki; Sessle, Barry J; Iwata, Koichi

    2016-01-01

    was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying. © The Author(s) 2016.

  10. Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

    Science.gov (United States)

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

    1987-12-01

    Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

  11. Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.

    Science.gov (United States)

    Leppanen, Jenni; Ng, Kah Wee; Tchanturia, Kate; Treasure, Janet

    2017-07-01

    Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations. Copyright © 2017. Published by Elsevier Ltd.

  12. Arterial compression of nerve is the primary cause of trigeminal neuralgia.

    Science.gov (United States)

    Chen, Guo-Qiang; Wang, Xiao-Song; Wang, Lin; Zheng, Jia-Ping

    2014-01-01

    Whether arterial or venous compression or arachnoid adhesions are primarily responsible for compression of the trigeminal nerve in patients with trigeminal neuralgia is unclear. The aim of this study was to determine the causes of trigeminal nerve compression in patients with trigeminal neuralgia. The surgical findings in patients with trigeminal neuralgia who were treated by micro vascular decompression were compared to those in patients with hemifacial spasm without any signs or symptoms of trigeminal neuralgia who were treated with microvascular decompression. The study included 99 patients with trigeminal neuralgia (median age, 57 years) and 101 patients with hemifacial spasm (median age, 47 years). There were significant differences between the groups in the relationship of artery to nerve (p relationship of vein to nerve. After adjustment for age, gender, and other factors, patients with vein compression of nerve or with artery compression of nerve were more likely to have trigeminal neuralgia (OR = 5.21 and 42.54, p = 0.026 and p compression of the trigeminal nerve is the primary cause of trigeminal neuralgia and therefore, decompression of veins need not be a priority when performing microvascular dissection in patients with trigeminal neuralgia.

  13. Trigeminal nerve anatomy in neuropathic and non-neuropathic orofacial pain patients.

    Science.gov (United States)

    Wilcox, Sophie L; Gustin, Sylvia M; Eykman, Elizabeth N; Fowler, Gordon; Peck, Christopher C; Murray, Greg M; Henderson, Luke A

    2013-08-01

    Trigeminal neuralgia, painful trigeminal neuropathy, and painful temporomandibular disorders (TMDs) are chronic orofacial pain conditions that are thought to have fundamentally different etiologies. Trigeminal neuralgia and neuropathy are thought to arise from damage to or pressure on the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. This study sought to assess the volume and microstructure of the trigeminal nerve in these 3 conditions. In 9 neuralgia, 18 neuropathy, 20 TMD, and 26 healthy controls, the trigeminal root entry zone was selected on high-resolution T1-weighted magnetic resonance images and the volume (mm(3)) calculated. Additionally, using diffusion-tensor images (DTIs), the mean diffusivity and fractional anisotropy values of the trigeminal nerve root were calculated. Trigeminal neuralgia patients displayed a significant (47%) decrease in nerve volume but no change in DTI values. Conversely, trigeminal neuropathy subjects displayed a significant (40%) increase in nerve volume but again no change in DTI values. In contrast, TMD subjects displayed no change in volume or DTI values. The data suggest that the changes occurring within the trigeminal nerve are not uniform in all orofacial pain conditions. These structural and volume changes may have implications in diagnosis and management of different forms of chronic orofacial pain. This study reveals that neuropathic orofacial pain conditions are associated with changes in trigeminal nerve volume, whereas non-neuropathic orofacial pain is not associated with any change in nerve volume. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  14. Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.

    Science.gov (United States)

    Steinman, Michael Q; Duque-Wilckens, Natalia; Greenberg, Gian D; Hao, Rebecca; Campi, Katharine L; Laredo, Sarah A; Laman-Maharg, Abigail; Manning, Claire E; Doig, Ian E; Lopez, Eduardo M; Walch, Keenan; Bales, Karen L; Trainor, Brian C

    2016-09-01

    Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Microstructural abnormalities in the trigeminal nerves of patients with trigeminal neuralgia revealed by multiple diffusion metrics

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Beijing Key laboratory of MRI and Brain Informatics, Beijing (China); Li, Jiping [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Duan, Yunyun; Zhang, Mo [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Li, Yongjie [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Yuqing, E-mail: yuqzhang@sohu.com [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2013-05-15

    Objective: To investigate microstructural tissue changes of trigeminal nerve (TGN) in patients with unilateral trigeminal neuralgia (TN) by multiple diffusion metrics, and correlate the diffusion indexes with the clinical variables. Methods: 16 patients with TN and 6 healthy controls (HC) were recruited into our study. All participants were imaged with a 3.0 T system with three-dimension time-of-flight (TOF) magnetic resonance angiography and fluid attenuated inversion recovery (FLAIR) DTI-sequence. We placed regions of interest over the root entry zone of the TGN and measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The mean values of FA, MD, AD and RD were compared between the affected and unaffected sides in the same patient, and to HC values. The correlation between the side-to-side diffusion metric difference and clinical variables (disease duration and visual analogy scale, VAS) was further explored. Results: Compared with the unaffected side and HC, the affected side showed significantly decreased FA and increased RD; however, no significant changes of AD were found. A trend toward significantly increased MD was identified on the affected side comparing with the unaffected side. We also found the significant correlation between the FA reduction and VAS of pain (r = −0.55, p = 0.03). Conclusion: DTI can quantitatively assess the microstructural abnormalities of the affected TGN in patients with TN. Our results suggest demyelination without significant axonal injury is the essential pathological basis of the affected TGN by multiple diffusion metrics. The correlation between FA reduction and VAS suggests FA as a potential objective MRI biomarker to correlate with clinical severity.

  16. Microstructural abnormalities in the trigeminal nerves of patients with trigeminal neuralgia revealed by multiple diffusion metrics

    International Nuclear Information System (INIS)

    Liu, Yaou; Li, Jiping; Butzkueven, Helmut; Duan, Yunyun; Zhang, Mo; Shu, Ni; Li, Yongjie; Zhang, Yuqing; Li, Kuncheng

    2013-01-01

    Objective: To investigate microstructural tissue changes of trigeminal nerve (TGN) in patients with unilateral trigeminal neuralgia (TN) by multiple diffusion metrics, and correlate the diffusion indexes with the clinical variables. Methods: 16 patients with TN and 6 healthy controls (HC) were recruited into our study. All participants were imaged with a 3.0 T system with three-dimension time-of-flight (TOF) magnetic resonance angiography and fluid attenuated inversion recovery (FLAIR) DTI-sequence. We placed regions of interest over the root entry zone of the TGN and measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The mean values of FA, MD, AD and RD were compared between the affected and unaffected sides in the same patient, and to HC values. The correlation between the side-to-side diffusion metric difference and clinical variables (disease duration and visual analogy scale, VAS) was further explored. Results: Compared with the unaffected side and HC, the affected side showed significantly decreased FA and increased RD; however, no significant changes of AD were found. A trend toward significantly increased MD was identified on the affected side comparing with the unaffected side. We also found the significant correlation between the FA reduction and VAS of pain (r = −0.55, p = 0.03). Conclusion: DTI can quantitatively assess the microstructural abnormalities of the affected TGN in patients with TN. Our results suggest demyelination without significant axonal injury is the essential pathological basis of the affected TGN by multiple diffusion metrics. The correlation between FA reduction and VAS suggests FA as a potential objective MRI biomarker to correlate with clinical severity

  17. An additional trigeminal system in certain snakes possessing infrared receptors

    NARCIS (Netherlands)

    Molenaar, Gerard J.

    1974-01-01

    This communication describes a nucleus and tract of the trigeminal system whose existence is not mentioned in any account of brain stem architecture known to the present author. The structures were first recognised in the brain stem of a giant snake (Python reticulatus) and later were also found

  18. Update on the challenges of treating trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Obermann M

    2015-04-01

    Full Text Available Mark Obermann Department of Neurology, University of Duisburg-Essen, Essen, Germany Abstract: Despite the multitude of treatment options currently available for trigeminal neuralgia, its management remains challenging in a considerable number of patients. The response to any particular treatment can be quite variable interindividually, and personalized treatment options are both resource-consuming and time-consuming. Anticonvulsant drugs, muscle relaxants, and neuroleptic agents are the preferred medical treatment for trigeminal neuralgia. Large placebo-controlled clinical trials are scarce, and no specific established substance has been developed for the treatment of trigeminal neuralgia. Promising new treatment options currently in clinical evaluation are botulinum neurotoxin type A injections and CNV1014802, a novel sodium channel blocker that selectively blocks the Nav1.7 sodium channel. Patients who do not respond to medical therapy may be eligible for more invasive treatment options, such as percutaneous Gasserian ganglion techniques, gamma knife surgery, and microvascular decompression. Keywords: trigeminal neuralgia, treatment, current, future, options, orphan drugs 

  19. Magnetic Resonance in trigeminal neuralgia: Presentation of three cases

    International Nuclear Information System (INIS)

    Ochoa Escudero, Martin; Echeverri Betancourt, Alejandro; Vargas Velez, Sergio Alberto

    2005-01-01

    Trigeminal neuralgia is characterized by episodes of acute facial pain. lt can be caused by diverse pathologies that affect anyone of the segments of the V cranial nerve. Magnetic resonance is of choice when imaging studies are necessary. Three cases evaluated by this modality and confirmed by surgery are shown

  20. Pain. Part 2a: Trigeminal Anatomy Related to Pain.

    Science.gov (United States)

    Renton, Tara; Egbuniwe, Obi

    2015-04-01

    In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

  1. Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway.

    Science.gov (United States)

    Pose, Inés; Silveira, Valentina; Morales, Francisco R

    2011-06-01

    Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Astringency is a trigeminal sensation that involves the activation of G protein-coupled signaling by phenolic compounds.

    Science.gov (United States)

    Schöbel, Nicole; Radtke, Debbie; Kyereme, Jessica; Wollmann, Nadine; Cichy, Annika; Obst, Katja; Kallweit, Kerstin; Kletke, Olaf; Minovi, Amir; Dazert, Stefan; Wetzel, Christian H; Vogt-Eisele, Angela; Gisselmann, Günter; Ley, Jakob P; Bartoshuk, Linda M; Spehr, Jennifer; Hofmann, Thomas; Hatt, Hanns

    2014-07-01

    Astringency is an everyday sensory experience best described as a dry mouthfeel typically elicited by phenol-rich alimentary products like tea and wine. The neural correlates and cellular mechanisms of astringency perception are still not well understood. We explored taste and astringency perception in human subjects to study the contribution of the taste as well as of the trigeminal sensory system to astringency perception. Subjects with either a lesion or lidocaine anesthesia of the Chorda tympani taste nerve showed no impairment of astringency perception. Only anesthesia of both the lingual taste and trigeminal innervation by inferior alveolar nerve block led to a loss of astringency perception. In an in vitro model of trigeminal ganglion neurons of mice, we studied the cellular mechanisms of astringency perception. Primary mouse trigeminal ganglion neurons showed robust responses to 8 out of 19 monomeric phenolic astringent compounds and 8 polymeric red wine polyphenols in Ca(2+) imaging experiments. The activating substances shared one or several galloyl moieties, whereas substances lacking the moiety did not or only weakly stimulate responses. The responses depended on Ca(2+) influx and voltage-gated Ca(2+) channels, but not on transient receptor potential channels. Responses to the phenolic compound epigallocatechin gallate as well as to a polymeric red wine polyphenol were inhibited by the Gαs inactivator suramin, the adenylate cyclase inhibitor SQ, and the cyclic nucleotide-gated channel inhibitor l-cis-diltiazem and displayed sensitivity to blockers of Ca(2+)-activated Cl(-) channels. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

    Science.gov (United States)

    Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

    2014-04-01

    Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

  4. Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

    Science.gov (United States)

    Spalink, Christy L; Barnes, Erin; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2017-08-01

    To report the use of intranasal dexmedetomidine, an α 2 -adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. Case series. Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

  5. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial.

    Science.gov (United States)

    Schmidt, H; Kern, W; Giese, R; Hallschmid, M; Enders, A

    2009-04-01

    The 22q13 deletion syndrome (Phelan-McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 deletion syndrome. We performed exploratory clinical trials in six children with 22q13 deletion syndrome who received intranasal insulin over a period of 1 year. Short-term (during the first 6 weeks) and long-term effects (after 12 months of treatment) on motor skills, cognitive functions, or autonomous functions, speech and communication, emotional state, social behaviour, behavioural disorders, independence in daily living and education were assessed. The children showed marked short-term improvements in gross and fine motor activities, cognitive functions and educational level. Positive long-term effects were found for fine and gross motor activities, nonverbal communication, cognitive functions and autonomy. Possible side effects were found in one patient who displayed changes in balance, extreme sensitivity to touch and general loss of interest. One patient complained of intermittent nose bleeding. We conclude that long-term administration of intranasal insulin may benefit motor development, cognitive functions and spontaneous activity in children with 22q13 deletion syndrome.

  6. Non-clinical safety evaluation of intranasal iota-carrageenan.

    Science.gov (United States)

    Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

    2015-01-01

    Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  7. Non-clinical safety evaluation of intranasal iota-carrageenan.

    Directory of Open Access Journals (Sweden)

    Alexandra Hebar

    Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  8. CILOSTAZOL INDUCES C-FOS EXPRESSION IN THE TRIGEMINAL NUCLEUS CAUDALIS AND BEHAVIOURAL CHANGES SUGGESTIVE OF HEADACHE WITH MIGRAINE-LIKE MANIFESTATIONS IN RATS

    DEFF Research Database (Denmark)

    Christensen, S. L. T.; Petersen, S.; Sorensen, D. B.

    2016-01-01

    in rats. Also, we tested the response to sumatriptan in order to evaluate the predictive properties of the model. Methods: The effect of cilostazol (125 mg/kg p.o.) was evaluated on a range of spontaneous behavioural parameters, light sensitivity and mechanical sensitivity thresholds. To assess headache...... specificity we evaluated the c-fos expression in the trigeminal nucleus caudalis. All experiments were done in female Sprague Dawley rats and the oestrous cycle was included in the analyses. Results: We found that cilostazol increased the light sensitivity and grooming behaviour of the rats and decreased......: The altered behaviours are suggestive of headache with migraine features, but not specific. The c-fos response in the trigeminal nucleus caudalis implies that the rats had pain originating from the head. The lack of response to sumatriptan disqualifies the model as predictive, but confirms the translation...

  9. Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

    Science.gov (United States)

    Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

    2016-02-01

    The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

  10. Intranasal delivery of antiviral siRNA.

    Science.gov (United States)

    Barik, Sailen

    2011-01-01

    Intranasal administration of synthetic siRNA is an effective modality of RNAi delivery for the prevention and therapy of respiratory diseases, including pulmonary infections. Vehicles used for nasal siRNA delivery include established as well as novel reagents, many of which have been recently optimized. In general, they all promote significant uptake of siRNA into the lower respiratory tract, including the lung. When properly designed and optimized, these siRNAs offer significant protection against respiratory viruses such as influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). Nasally administered siRNA remains within the lung and does not access systemic blood flow, as judged by its absence in other major organs such as liver, heart, kidney, and skeletal muscle. Adverse immune reaction is generally not encountered, especially when immunogenic and/or off-target siRNA sequences and toxic vehicles are avoided. In fact, siRNA against RSV has entered Phase II clinical trials in human with promising results. Here, we provide a standardized procedure for using the nose as a specific route for siRNA delivery into the lung of laboratory animals. It should be clear that this simple and efficient system has enormous potential for therapeutics.

  11. Orofacial neuropathic pain induced by oxaliplatin: downregulation of KCNQ2 channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel potentiator retigabine.

    Science.gov (United States)

    Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav; Kanda, Hirosato; Gu, Jianguo G

    2017-01-01

    Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.

  12. Early trigeminal nerve involvement in Listeria monocytogenes rhombencephalitis

    DEFF Research Database (Denmark)

    Karlsson, William K; Harboe, Zitta Barrella; Roed, Casper

    2017-01-01

    dysfunction on that side. In addition, we identified another 120 cases of Listeria rhombencephalitis following a systematic review. Cranial nerves VII, V, IX, and X, respectively, medulla oblongata, cerebellum and pons, were the most frequently involved brain structures. The present clinical and radiological...... findings corroborate earlier data from animal experiments, indicating that L. monocytogenes may be capable of retrograde intra-axonal migration along the cranial nerves. We suggest that in a subset of patients with rhombencephalitis L. monocytogenes enters the cerebellopontine angle through the trigeminal......Listeria monocytogenes is associated with rhombencephalitis. However, the exact mechanisms of brainstem invasion remains poorly understood. Here, we demonstrate clinical and radiological data suggesting that Listeria may invade the brainstem via the trigeminal nerve. Three females (41, 64 and 70...

  13. Isolated intermittent vertigo: A presenting feature of persistent trigeminal artery

    Directory of Open Access Journals (Sweden)

    Rajsrinivas Parthasarathy

    2016-01-01

    Full Text Available Embryonic carotid – basilar anastomosis when persistent in adult life can present with a variety of neurological symptoms. We present a patient with isolated intermittent vertigo attributable to the embryonic anastomosis and describe the different types of persistent trigeminal artery. A 76-year-old Caucasian man presented with isolated intermittent vertigo and symptoms suggestive of anterior and posterior circulation strokes. Impaired vasomotor reactivity was demonstrated on insonation of the anterior and posterior cerebral arteries in this patient with a persistent left trigeminal artery and 75% stenosis of the left internal carotid artery (ICA. The symptom of intermittent vertigo resolved with carotid endarterectomy. Decreased flow across the stenotic segment of the ICA which subserved the posterior circulation resulted in basilar insufficiency. Hypoperfusion to the flocculonodular lobe supplied by the anterior inferior cerebellar artery is a likely cause for the intermittent vertigo.

  14. Intracranial Management of Perineural Spread in the Trigeminal Nerve.

    Science.gov (United States)

    Redmond, Michael J; Panizza, Benedict J

    2016-04-01

    Since the mid-1960s surgeons have attempted to cure intracranial perineural spread (PNS) of cutaneous malignancies. Untreated patients with trigeminal PNS die from brainstem invasion and leptomeningeal disease. It was understood that resection with clear margins was potentially curative, but early surgical attempts were unsuccessful. The prevailing wisdom considered that this surgery failed to improve the results achieved with radiation therapy alone and was associated with high morbidity. However, with improved imaging, surgical equipment, and better understanding of cavernous sinus (CS) anatomy and access, contemporary surgeons can improve outcomes for this disease. The aim of this paper is to describe a technique to access the interdural compartment of the CS and treat PNS of cutaneous squamous cell carcinoma (cSCC) in the intracranial trigeminal nerve and ganglion. It is based on the experience of the Queensland Skull Base Unit, Australia in managing PNS of cutaneous squamous cell carcinoma of the head and neck (cSCCHN).

  15. Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.

    Science.gov (United States)

    Muzyka, Iryna M; Estephan, Bachir

    2018-01-01

    The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.

  16. Effect of beam channel plugging on the outcome of gamma knife radiosurgery for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Massager, Nicolas; Nissim, Ouzi; Murata, Noriko; Devriendt, Daniel; Desmedt, Francoise; Vanderlinden, Bruno; Regis, Jean; Levivier, Marc

    2006-01-01

    Purpose: We studied the influence of using plugs for brainstem protection during gamma knife radiosurgery (GKR) of trigeminal neuralgia (TN), with special emphasis on irradiation doses delivered to the trigeminal nerve, pain outcomes, and incidence of trigeminal dysfunction. Methods and Materials: A GKR procedure for TN using an anterior cisternal target and a maximum dose of 90 Gy was performed in 109 patients. For 49 patients, customized beam channel blocking (plugs) were used to reduce the dose delivered to the brainstem. We measured the mean and integrated radiation doses delivered to the trigeminal nerve and the clinical course of patients treated with and without plugs. Results: We found that blocking increases the length of trigeminal nerve exposed to high-dose radiation, resulting in a significantly higher mean dose to the trigeminal nerve. Significantly more of the patients with blocking achieved excellent pain outcomes (84% vs. 62%), but with higher incidences of moderate and bothersome trigeminal nerve dysfunction (37% mild/10% bothersome with plugs vs. 30% mild/2% bothersome without). Conclusions: The use of plugs to protect the brainstem during GKR treatment for TN increases the dose of irradiation delivered to the intracisternal trigeminal nerve root and is associated with an important increase in the incidence of trigeminal nerve dysfunction. Therefore, beam channel blocking should be avoided for 90 Gy-GKR of TN

  17. Results of Percutaneous Balloon Compression in Trigeminal Pain Syndromes.

    Science.gov (United States)

    Grewal, Sanjeet S; Kerezoudis, Panagiotis; Garcia, Oscar; Quinones-Hinojosa, Alfredo; Reimer, Ronald; Wharen, Robert E

    2018-06-01

    To investigate initial pain relief and subsequent recurrence after percutaneous balloon compression (PBC) and describe its association with the nature of trigeminal pain, previous procedures, or other clinical factors. A total of 222 patients with medically refractory trigeminal pain treated with PBC at Mayo Clinic Florida between 1998 and 2017 were enrolled into this study. Patients were divided into those with typical trigeminal neuralgia (TN) and those with atypical trigeminal pain. The postprocedural rate of pain recurrence and associations between patient characteristics and recurrence were studied. One hundred fifty-two patients had TN and 70 patients had atypical pain. At the last follow-up, 158 patients had excellent pain relief, 37 had good pain relief, 11 had fair pain relief, and 16 had poor pain relief. The median duration of follow-up was 31.1 months. Patients with atypical pain were less likely to have an excellent result compared with patients with typical pain (61.4% vs. 82.9%; P < 0.001). Recurrence was observed in 103 patients (46.4%) and was associated with previous procedures (hazard ratio, 1.658; 95% confidence interval, 1.09-2.49; P = 0.017). Other clinical factors were not significant. Our study demonstrates the safety and efficacy of PBC, with 88% of patients pain-free at last follow-up. Patients with atypical pain have worse outcomes, and patients with previous procedures have a higher risk of recurrence. Repeat surgery does not decrease efficacy. We recommend conservative parameter selection at the initial procedure. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Immediate pain relief by microvascular decompression for idiopathic trigeminal neuralagia

    International Nuclear Information System (INIS)

    Haq, N.U.; Ali, M.; Khan, H.M.; Ishaq, M.; Khattak, M.I.

    2016-01-01

    Background: Trigeminal neuralgia is a common entity which is managed by neurosurgeons in day to day practice. Up-till now many treatment options have been adopted for it but micro-vascular decompression is much impressive in terms of pain control and recurrence rate in all of them. The objective of study was known the efficacy of micro vascular decompression for idiopathic trigeminal neuralgia by using muscle patch in terms of immediate pain relief. Methods: This descriptive study was carried out in Neurosurgery Department lady reading hospital, Peshawar from January 2010 to December 2012. All patients who underwent micro vascular decompression for idiopathic trigeminal neuralgia were included in the study. Patients were assessed 72 hours after the surgery by borrow neurological institute pain scale (BNIP scale) for pain relief and findings were documented on predesigned proforma. Data was analysed by SPSS-17. Results: Total 52 patients were included in this study. Among these 32 (61.53 percentage) were female and 20 (38.46 percentage) were males having age from 22-76 years (mean 49 years). Right side was involved in 36 (69.23 percentage) and left side in 16 (30.76 percentage) patients. Duration of symptoms ranged from 6 months to 16 years (mean 8 years). History of dental extraction and peripheral neurectomy was present in 20 (38 percentage) and 3(5.76 percentage) patients while V3 was most commonly involved branch with 28(57.69 percentage) frequency and combined V2,V3 involvement was 1 (11.53 percentage). Superior cerebellar artery was most common offending vessel in 46(88.46 percentage) while arachnoid adhesions were in 2(3.84 percentage) patients. We assessed patient immediate postoperatively using BNIP pain scale. Conclusion: Micro-vascular decompression is most effective mode of treatment for trigeminal neuralgia in terms of immediate pain relief. (author)

  19. Trigeminal complications arising after surgery of cranial base meningiomas.

    Science.gov (United States)

    Westerlund, Ulf; Linderoth, Bengt; Mathiesen, Tiit

    2012-04-01

    Chronic severe facial pain is a feared sequel of cranial base surgery. This study explores the symptomatology, incidence and impact on the individual of postoperative de novo trigeminal nerve affection as well as the recovery potential. Out of 231 patients operated for cranial base meningiomas at the Karolinska University Hospital during 7 years, 25 complained of de novo trigeminal symptoms at clinical follow-up 3 months after surgery. Six were later lost to follow-up leaving 19 participants in the study, which was conducted using a questionnaire and a structured telephone interview. All patients complained of facial numbness, affecting the V1 branch in 10/19 patients (53%), the V2 branch in 18/19 (95%) and the V3 branch in 9/19 (47%). Surprisingly, only three (16%) suffered from trigeminal pain, which could be adequately managed by pharmacotherapy. However, five patients (26%) demonstrated ocular dysaesthetic problems. Twelve (63%) described their handicap to be mild, while seven (37%) had daily or severe symptoms. Five patients (26%) reported no improvement over time, while nine (47%) showed improvement and four (21%) stated good recovery. Only one patient (5%) claimed complete symptom remission. In the present study, 11% of the patients presented with a de novo postoperative affection of the trigeminal nerve after removal of a cranial base meningioma; 37% of these reported daily/severe symptoms. Only 26% showed good recovery, observed in patients without tumour infiltration of the nerve or intraoperative nerve damage. In spite of frequent complaints of numbness, pain was uncommon (16%) and often manageable by pharmacotherapy, while ocular symptoms turned out to be more frequent and more disabling than expected.

  20. Cytoarchitectonic study of the trigeminal ganglion in humans

    Science.gov (United States)

    KRASTEV, DIMO STOYANOV; APOSTOLOV, ALEXANDER

    2013-01-01

    The trigeminal ganglion (TG), a cluster of pseudounipolar neurons, is located in the trigeminal impression of the temporal pyramid. It is covered by a sheath of the dura mater and arachnoid and is near the rear end of the cavernous sinus. The peripheral processes of the pseudounipolar cells are involved in the formation of the first and second branch and the sensory part of the third branch of the fifth cranial nerve, and the central ones form the sensory root of the nerve, which penetrates at the level of the middle cerebellar peduncle, aside from the pons, and terminate in the sensory nuclei of the trigeminal complex. We found that the primary sensory neurons involved in sensory innervation of the orofacial complex are a diverse group. Although they possess the general structure of pseudounipolar neurons, there are significant differences among them, seen in varying intensities of staining. Based on our investigations we classified the neurons into 7 groups, i.e. large, subdivided into light and dark, medium, also light and dark, and small light and dark, and, moreover, neurons with an irregular shape of their perikarya. Further research by applying various immunohistochemical methods will clarify whether differences in the morphological patterns of the neurons are associated with differences in the neurochemical composition of various neuronal types. PMID:26527926

  1. Agreeable smellers and sensitive neurotics--correlations among personality traits and sensory thresholds.

    Science.gov (United States)

    Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N B; Hummel, Thomas

    2011-04-27

    Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality.

  2. Agreeable Smellers and Sensitive Neurotics – Correlations among Personality Traits and Sensory Thresholds

    Science.gov (United States)

    Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N. B.; Hummel, Thomas

    2011-01-01

    Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality. PMID:21556139

  3. Agreeable smellers and sensitive neurotics--correlations among personality traits and sensory thresholds.

    Directory of Open Access Journals (Sweden)

    Ilona Croy

    Full Text Available Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124 completed a personality inventory (NEO-FFI and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality.

  4. Removing intranasal splints after septal surgery.

    Science.gov (United States)

    Aksoy, Elif; Serin, Gediz Murat; Polat, Senol; Kaytaz, Asm

    2011-05-01

    The aim of this retrospective chart review of the patients who had septal surgery with or without turbinate surgery was to compare the postoperative complication rates according to the time of intranasal-splint (INS) removal. The data of 137 patients who underwent septal surgery with or without turbinate surgery at 2 different hospitals of Acıbadem Health Care Group between January 2007 and March 2009 were retrospectively evaluated. The patients who had these risk factors were eliminated, and 96 patients were included in this study. The patients were divided into 2 groups according to splint-removal time. The first group comprises patients whose nasal splints were removed in 24 hours after surgery, and the second group comprises patients whose splints were removed 5 days after the surgery. Any bleeding, septal hematoma, and synechia after pack removal were recorded. Analysis of the rate of complications was done with the χ test. Sixty-five male and 31 female patients with a mean age of 32.4 years (range, 18-57 years) were included in the study groups. Septal surgeries were performed in association with turbinate surgery in all 96 patients. These patients were divided into 2 groups. In the first group (n = 50), INSs were removed in 24 hours after surgery. In the second group (n = 46), INSs were removed 5 days after surgery. Bleeding within the first postoperative week was not recorded in both groups. Late bleeding was recorded in 2% (n = 1) of group 1 and in 2.17% (n = 1) in group 2. Septal hematoma and synechia were not recorded in none of the groups. The results were not statistically significant (P = 1). The routine use of INSs after septoplasty and removing them 24 hours after septoplasty are sufficient to avoid postoperative complications, and it minimizes postoperative discomfort.

  5. Glucose recovery after intranasal glucagon during hypoglycaemia in man

    DEFF Research Database (Denmark)

    Hvidberg, A; Djurup, R; Hilsted, J

    1994-01-01

    to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i...... endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose...... concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose...

  6. Iatrogenic Cushing's syndrome caused by intranasal steroid use.

    Science.gov (United States)

    Dursun, Fatma; Kirmizibekmez, Heves

    2017-01-01

    Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

  7. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    Science.gov (United States)

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  8. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  9. A case of trigeminal hypersensitivity after administration of intrathecal sufentanil and bupivacaine for labor analgesia

    Directory of Open Access Journals (Sweden)

    Adriano Bechara de Souza Hobaika

    2014-01-01

    Full Text Available Rostral spread of intrathecal drugs and sensitization of supraspinal sites may provoke several adverse effects. This case describes a patient with right hemifacial paresthesia, trismus and dysphasia on the trigeminal nerve distribution after intrathecal sufentanil administration. Primigravida, 34 years, 39 weeks of pregnancy, with hypothyroidism and pregnancy induced hypertension. Allergic to latex. In the use of puran T4, 50 μg /day. When the patient presented cervical dilatation of 4 cm, she requested analgesia. She was placed in the sitting position and a spinal puncture was performed with a 27G needle pencil point in L4/L5 (1.5 mg of bupivacaine plus 7.5 μg of sufentanil. Next, was performed an epidural puncture in the same space. It was injected bupivacaine 0.065%, 10 ml, to facilitate the passage of the catheter. After 5 min lying down in the lateral upright position, she complained of perioral and right hemifacial paresthesia, mainly maxillary and periorbital, as well as trismus and difficulty to speak. The symptoms lasted for 30 min and resolved spontaneously. After 1 h, patient requested supplementary analgesia (12 ml of bupivacaine 0.125% and a healthy baby girl was born. Temporary mental alterations have been described with the use of fentanyl and sufentanil in combined epidural-spinal analgesia, such as aphasia, difficulty of swallowing, mental confusion and even unconsciousness. In this patient, facial areas with paresthesia indicated by patient appear in clear association with the ophthalmic and maxillary branches of the trigeminal nerve and the occurrence of trismus and dysphagia are in association with the mandibular motor branch. The exact mechanism of rostral spread is not known, but it is speculated that after spinal drug administration, a subsequent epidural dose may reduce the intratecal space and propel the drug into the supraspinal sites.

  10. A rare cause of hyperprolactinemia: persistent trigeminal artery with stalk-section effect

    International Nuclear Information System (INIS)

    Ekinci, G.; Baltacioglu, F.; Cimsit, C.; Akpinar, I.; Erzen, C.; Kilic, T.; Pamir, N.

    2001-01-01

    The primitive trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries are fetal anastomoses between the carotid and vertebrobasilar systems. Persistent trigeminal artery (PTA) is the most frequent embryonic communication between the vertebrobasilar and carotid systems in adults. We report a case of PTA compressing the left side of the pituitary gland and stalk, in a patient with elevated blood prolactin level. (orig.)

  11. A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma.

    Science.gov (United States)

    Frisardi, Gianni; Iani, Cesare; Sau, Gianfranco; Frisardi, Flavio; Leornadis, Carlo; Lumbau, Aurea; Enrico, Paolo; Sirca, Donatella; Staderini, Enrico Maria; Chessa, Giacomo

    2013-10-28

    In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions.

  12. Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine

    Directory of Open Access Journals (Sweden)

    Franceschini Alessia

    2012-11-01

    Full Text Available Abstract Background Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT or knock-in (KI mice expressing the Cacna1a gene mutation (R192Q found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. Results KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Conclusions Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.

  13. Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine.

    Science.gov (United States)

    Franceschini, Alessia; Nair, Asha; Bele, Tanja; van den Maagdenberg, Arn Mjm; Nistri, Andrea; Fabbretti, Elsa

    2012-11-21

    Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.

  14. [Trigeminal purinergic P2X4 receptor involved in experimental occlusal interference-induced hyperalgesia in rat masseter muscle].

    Science.gov (United States)

    Xu, Xiaoxiang; Cao, Ye; Ding, Tingting; Fu, Kaiyuan; Xie, Qiufei

    2016-03-01

    To explore the expression of purinergic p2X4 receptor (P2X4R) in trigeminal ganglion of rats after occlusal interference. Investigation of peripheral receptor mechanism of occlusal interference-induced masticatory muscle pain will aid the development of drug intervention against this condition. Experimental occlusal interference was established by application of 0.4 mm metal crown to the upper right first molar of male Sprague-Dawley rats. Real-time PCR assay was used to investigate P2X4R mRNA level in trigeminal ganglion in rats with occlusal interference for 3, 7, 10 and 14 days and in control rats without occlusal interference (n=5 in each). Retrograde labelling combining immunofluorescence was performed to evaluate the percentage of P2X4R-positive cells in masseter afferent neurons (n=5 in each group). Graded concentrations of P2XR antagonist TNP-ATP (0.1, 10, 125, 250, 500 μmol/L) or saline (n=5 in each group) was administrated in right masseter and the mechanical sensitivity of bilateral masseters was measured before occlusal interference application, before the injection, and 30 min as well as 60 min after the injection. Compared with control rats (P2X4R mRNA: right side: 1.00±0.26, left side: 0.94± 0.21; percentage of P2X4R-positive masseter afferents: right side: [64.3±6.3]%, left side: [67.7±5.8]%), the level of P2X4R mRNA in bilateral trigeminal ganglia (right side: 5.98±3.56; left side: 5.06±2.88) of rats with occlusal interference for 7 days up-regulated (Pocclusal interference-induced masseter hyperalgesia.

  15. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need

  16. Trigeminal cardiac reflex and cerebral blood flow regulation

    Directory of Open Access Journals (Sweden)

    Dominga Lapi

    2016-10-01

    Full Text Available The stimulation of some facial regions is known to trigger the trigemino-cardiac reflex: the main stimulus is represented by the contact of the face with water. This phenomenon called diving reflex induces a set of reactions in the cardiovascular and respiratory systems occurring in all mammals, especially marine (whales, seals. During the immersion of the face in the water, the main responses are aimed at reducing the oxygen consumption of the organism. Accordingly reduction in heart rate, peripheral vasoconstriction, blood pooling in certain organs, especially the heart and brain, and an increase in blood pressure have been reported. Moreover, the speed and intensity of the reflex is inversely proportional to the temperature of the water: more cold the water, more reactions as described are strong. In the case of deep diving an additional effect, such as blood deviation, has been reported: the blood is requested within the lungs, to compensate for the increase in the external pressure, preventing them from collapsing.The trigeminal-cardiac reflex is not just confined to the diving reflex; recently it has been shown that a brief proprioceptive stimulation (10 min by jaw extension in rats produces interesting effects both at systemic and cerebral level, reducing the arterial blood pressure and vasodilating the pial arterioles. The arteriolar dilation is associated with rhythmic diameter changes characterized by an increase in the endothelial activity. Fascinating the stimulation of trigeminal nerve is able to activated the nitric oxide release by vascular endothelial. Therefore the aim of this review was to highlight the effects due to trigeminal cardiac reflex induced by a simple mandibular extension, because produced opposite effects compared to those elicited by the diving reflex as it induces hypotension and modulation of cerebral arteriolar tone.

  17. Predictors of Trigeminal Neuropathy After Radiosurgery for Vestibular Schwannomas

    Energy Technology Data Exchange (ETDEWEB)

    Senova, Suhan [Unité de Radiochirurgie Gamma Knife, Region Ile De France, Paris (France); Service de Neurochirurgie, Centre Hospitalier Universitaire (CHU) La Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris (France); Inserm, U955, Equipe 14, Université Paris Est, Faculté de médecine, Créteil (France); Aggad, Mourad [Unité de Radiochirurgie Gamma Knife, Region Ile De France, Paris (France); Service de Neurochirurgie, Centre Hospitalier Universitaire (CHU) La Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris (France); Golmard, Jean-Louis [Service de Biostatistiques, CHU La Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris (France); Hasboun, Dominique [Service de Neuroanatomie, CHU La Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris (France); Lamproglou, Ioannis [Unité de Radiochirurgie Gamma Knife, Region Ile De France, Paris (France); and others

    2016-06-01

    Purpose: To analyze the relationship between dosimetric characteristics and symptoms related to trigeminal neuropathy (TN) observed after radiosurgery (RS) for vestibular schwannomas (VS); to propose guidelines to optimize planification in VS RS regarding TN preservation; and to detail the mechanism of TN impairment after VS RS. Methods and Materials: One hundred seventy-nine patients treated between 2011 and 2013 for VS RS and without trigeminal impairment before RS were included in a retrospective study. Univariate and multivariate analyses were performed to determine predictors of TN among characteristics of the patients, the dosimetry, and the VS. Results: There were 20 Koos grade 1, 99 grade 2, 57 grade 3, and 3 grade 4. Fourteen patients (7.8%) presented a transitory or permanent TN. Between the patients with and without TN after VS RS, there was no significant difference regarding dosimetry or VS volume itself. Significant differences (univariate analysis P<.05, Mann-Whitney test) were found for parameters related to the cisternal portion of the trigeminal nerve: total integrated dose, maximum dose, mean dose, volume of the Vth nerve (Vol{sub v}), and volume of the Vth nerve receiving at least 11 Gy (Vol{sub Vcist>11Gy}), but also for maximal dose to the Vth nerve nucleus and intra-axial portion (Dose max{sub Vax}). After multivariate analysis, the best model predicting TN included Vol{sub Vcist>11Gy} (P=.0045), Dose max{sub Vax} (P=.0006), and Vol{sub v} (P=.0058). The negative predictive value of this model was 97%. Conclusions: The parameters Vol{sub Vcist>11Gy}, Dose max{sub Vax}, and Vol{sub v} should be checked when designing dosimetry for VS RS.

  18. Treatment strategy for trigeminal neuralgia: a thirty years experience.

    Science.gov (United States)

    Broggi, Giovanni; Ferroli, Paolo; Franzini, Angelo

    2008-05-01

    Trigeminal neuralgia is an invalidating disease when become drug-resistant. The only possible treatment is surgery with different modalities, percutaneous, open surgery or radiosurgery. The thirty years experience at the Fondazione Istituto Neurologico C. Besta, Milano, Italy suggests that these surgical strategies are successful in pain control in short and long term period in more than 90% of cases, with a low rate of side effects and high improvement of quality of life. The type of surgery should be tailored on the particular patient considering age, general physical condition, neuroradiological assessment in which MRI with dedicated sequences are mandatory, and also patient's attitude.

  19. Neurogenic inflammation: a study of rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Kristiansen, Kim Anker; Edvinsson, Lars

    2010-01-01

    Calcitonin gene-related peptide (CGRP) is linked to neurogenic inflammation and to migraine. Activation of the trigeminovascular system plays a prominent role during migraine attacks with the release of CGRP. The trigeminal ganglion (TG) contains three main cell types: neurons, satellite glial...... cells (SGC) and Schwann cells; the first two have before been studied in vitro separately. Culture of rat TG provides a method to induce inflammation and the possibility to evaluate the different cell types in the TG simultaneously. We investigated expression levels of various inflammatory cytokines...

  20. Electrophysiological Features of Neurons in the Mesencephalic Trigeminal Nuclei

    Directory of Open Access Journals (Sweden)

    Jun-Ling Xing

    2015-01-01

    Full Text Available Mesencephalic trigeminal nucleus (Mes V neurons represent an uncommon class of primary sensory neurons. Besides receiving somatosensory information, Mes V neurons are also involved in regulating multisensory information. The present review first describes the passive features as well as three important currents, followed by a distinct excitability classification and a description of the excitability transition of Mes V neurons. Furthermore, their resonance property, the existence of membrane oscillation and electrical coupling which may promote strong synchronization, as well as their function in controlling stretch reflex activity, are discussed.

  1. Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

    Science.gov (United States)

    Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

    2016-10-01

    This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Intranasal localizability of odorants: influence of stimulus volume.

    Science.gov (United States)

    Frasnelli, J; Hummel, T; Berg, J; Huang, G; Doty, R L

    2011-05-01

    When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.

  3. Detection of compression vessels in trigeminal neuralgia by surface-rendering three-dimensional reconstruction of 1.5- and 3.0-T magnetic resonance imaging.

    Science.gov (United States)

    Shimizu, Masahiro; Imai, Hideaki; Kagoshima, Kaiei; Umezawa, Eriko; Shimizu, Tsuneo; Yoshimoto, Yuhei

    2013-01-01

    Surface-rendered three-dimensional (3D) 1.5-T magnetic resonance (MR) imaging is useful for presurgical simulation of microvascular decompression. This study compared the sensitivity and specificity of 1.5- and 3.0-T surface-rendered 3D MR imaging for preoperative identification of the compression vessels of trigeminal neuralgia. One hundred consecutive patients underwent microvascular decompression for trigeminal neuralgia. Forty and 60 patients were evaluated by 1.5- and 3.0-T MR imaging, respectively. Three-dimensional MR images were constructed on the basis of MR imaging, angiography, and venography data and evaluated to determine the compression vessel before surgery. MR imaging findings were compared with the microsurgical findings to compare the sensitivity and specificity of 1.5- and 3.0-T MR imaging. The agreement between MR imaging and surgical findings depended on the compression vessels. For superior cerebellar artery, 1.5- and 3.0-T MR imaging had 84.4% and 82.7% sensitivity and 100% and 100% specificity, respectively. For anterior inferior cerebellar artery, 1.5- and 3.0-T MR imaging had 33.3% and 50% sensitivity and 92.9% and 95% specificity, respectively. For the petrosal vein, 1.5- and 3.0-T MR imaging had 75% and 64.3% sensitivity and 79.2% and 78.1% specificity, respectively. Complete pain relief was obtained in 36 of 40 and 55 of 60 patients undergoing 1.5- and 3.0-T MR imaging, respectively. The present study showed that both 1.5- and 3.0-T MR imaging provided high sensitivity and specificity for preoperative assessment of the compression vessels of trigeminal neuralgia. Preoperative 3D imaging provided very high quality presurgical simulation, resulting in excellent clinical outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Primary nerve-sheath tumours of the trigeminal nerve: clinical and MRI findings

    International Nuclear Information System (INIS)

    Majoie, C.B.L.M.; Hulsmans, F.J.H.; Sie, L.H.; Castelijns, J.A.; Valk, J.; Walter, A.; Albrecht, K.W.

    1999-01-01

    We reviewed the clinical and MRI findings in primary nerve-sheath tumours of the trigeminal nerve. We retrospectively reviewed the medical records, imaging and histological specimens of 10 patients with 11 primary tumours of the trigeminal nerve. We assessed whether tumour site, size, morphology or signal characteristics were related to symptoms and signs or histological findings. Histological proof was available for 8 of 11 tumours: six schwannomas and two plexiform neurofibromas. The other three tumours were thought to be schwannomas, because they were present in patients with neurofibromatosis type 2 and followed the course of the trigeminal nerve. Uncommon MRI appearances were observed in three schwannomas and included a large intratumoral haemorrhage, a mainly low-signal appearance on T2-weighted images and a rim-enhancing, multicystic appearance. Only four of nine schwannomas caused trigeminal nerve symptoms, including two with large cystic components, one haemorrhagic and one solid tumor. Of the five schwannomas which did not cause any trigeminal nerve symptoms, two were large. Only one of the plexiform neurofibromas caused trigeminal nerve symptoms. Additional neurological symptoms and signs, not related to the trigeminal nerve, could be attributed to the location of the tumour in three patients. (orig.)

  5. Preoperative evaluation of neurovascular relationship by using contrast-enhanced and unenhanced 3D time-of-flight MR angiography in patients with trigeminal neuralgia

    International Nuclear Information System (INIS)

    Qin, Zhou; Zhiling, Liu; Chuanfu, Li; Qingshi Zeng; Chuncheng, Qu; Shilei, Ni

    2011-01-01

    Background Microvascular decompression is an etiological strategy for the therapy of trigeminal neuralgia (TN). Preoperative identification of neurovascular compression, therefore, could have an impact on the determination of appropriate treatment for TN. Purpose To evaluate the value of contrast-enhanced and unenhanced three-dimensional (3D) time-of-flight (TOF) MR angiography in the visualization of neurovascular relationship in patients with TN. Material and Methods Thirty-seven patients with unilateral TN underwent unenhanced and contrast-enhanced 3D TOF MR angiography with a 3.0-T MR system. Images were reviewed by a radiologist blinded to clinical details. Vascular contact with the trigeminal nerve was identified, and the nature of the involved vessels (artery or vein) was determined. All patients underwent microvascular decompression. Results In 37 patients with TN, contrast-enhanced 3D TOF MR angiography identified surgically verified neurovascular contact in 35 of 36 symptomatic nerves, and there was no false-positive. Based on surgical findings, the sensitivity of MR imaging was 97.2% and specificity 100%. The nature of the offending vessel was correctly identified in 94.4% of the patients by using the combination of contrast-enhanced and unenhanced MR angiography. Conclusion Contrast-enhanced 3D TOF MR angiography is useful in the detection of vascular contact with the trigeminal nerve in patients with TN, and this MR imaging in combination with unenhanced MR angiography could help in the identification of the nature of the responsible vessels

  6. Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis.

    Science.gov (United States)

    Sugiyama, Atsuhiko; Mori, Masahiro; Masuda, Hiroki; Uchida, Tomohiko; Muto, Mayumi; Uzawa, Akiyuki; Ito, Shoichi; Kuwabara, Satoshi

    2015-08-15

    Trigeminal root entry zone abnormality on brain magnetic resonance imaging has been frequently reported in multiple sclerosis patients, but it has not been investigated in neuromyelitis optica patients. Brain magnetic resonance imaging of 128 consecutive multiple sclerosis patients and 46 neuromyelitis optica patients was evaluated. Trigeminal root entry zone abnormality was present in 11 (8.6%) of the multiple sclerosis patients and two (4.3%) of the neuromyelitis optica patients. The pontine trigeminal root entry zone may be involved in both multiple sclerosis and neuromyelitis optica. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

    Science.gov (United States)

    Tietze, Karen J.

    1990-01-01

    Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

  8. Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal neurons and their modulation by NGF or serotonin

    Directory of Open Access Journals (Sweden)

    Giniatullin Rashid

    2006-03-01

    Full Text Available Abstract Background Cultured sensory neurons are a common experimental model to elucidate the molecular mechanisms of pain transduction typically involving activation of ATP-sensitive P2X or capsaicin-sensitive TRPV1 receptors. This applies also to trigeminal ganglion neurons that convey pain inputs from head tissues. Little is, however, known about the plasticity of these receptors on trigeminal neurons in culture, grown without adding the neurotrophin NGF which per se is a powerful algogen. The characteristics of such receptors after short-term culture were compared with those of ganglia. Furthermore, their modulation by chronically-applied serotonin or NGF was investigated. Results Rat or mouse neurons in culture mainly belonged to small and medium diameter neurons as observed in sections of trigeminal ganglia. Real time RT-PCR, Western blot analysis and immunocytochemistry showed upregulation of P2X3 and TRPV1 receptors after 1–4 days in culture (together with their more frequent co-localization, while P2X2 ones were unchanged. TRPV1 immunoreactivity was, however, lower in mouse ganglia and cultures. Intracellular Ca2+ imaging and whole-cell patch clamping showed functional P2X and TRPV1 receptors. Neurons exhibited a range of responses to the P2X agonist α, β-methylene-adenosine-5'-triphosphate indicating the presence of homomeric P2X3 receptors (selectively antagonized by A-317491 and heteromeric P2X2/3 receptors. The latter were observed in 16 % mouse neurons only. Despite upregulation of receptors in culture, neurons retained the potential for further enhancement of P2X3 receptors by 24 h NGF treatment. At this time point TRPV1 receptors had lost the facilitation observed after acute NGF application. Conversely, chronically-applied serotonin selectively upregulated TRPV1 receptors rather than P2X3 receptors. Conclusion Comparing ganglia and cultures offered the advantage of understanding early adaptive changes of nociception

  9. Maresin 1 Inhibits TRPV1 in Temporomandibular Joint-Related Trigeminal Nociceptive Neurons and TMJ Inflammation-Induced Synaptic Plasticity in the Trigeminal Nucleus

    Directory of Open Access Journals (Sweden)

    Chul-Kyu Park

    2015-01-01

    Full Text Available In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ. Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage-derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1 in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye, I showed that maresin 1 potently inhibits capsaicin-induced TRPV1 currents and neuronal activity via Gαi-coupled G-protein coupled receptors in DiI-labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist-evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation-induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ-inflammatory pain in the orofacial region.

  10. Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

    Science.gov (United States)

    2017-10-01

    HOPKINS UNIVERSITY, THE 3400 N CHARLES ST W400 WYMAN PARK BLDG BALTIMORE MD 21218-2680 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10...people with MS. The study will also evaluate the impact of intranasal insulin on measures of oxidative stress, axonal injury, cellular stress...and energy metabolism in MS. The design of this phase I/II, randomized, double-blind, placebo-controlled trial is as follows; 105participants will be

  11. Intranasal dexmedetomidine for sedation for pediatric computed tomography imaging.

    Science.gov (United States)

    Mekitarian Filho, Eduardo; Robinson, Fay; de Carvalho, Werther Brunow; Gilio, Alfredo Elias; Mason, Keira P

    2015-05-01

    This prospective observational pilot study evaluated the aerosolized intranasal route for dexmedetomidine as a safe, effective, and efficient option for infant and pediatric sedation for computed tomography imaging. The mean time to sedation was 13.4 minutes, with excellent image quality, no failed sedations, or significant adverse events. Registered with ClinicalTrials.gov: NCT01900405. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  13. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    Science.gov (United States)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  14. Effects of Sex and Stress on Trigeminal Neuropathic Pain-Like Behavior in Rats.

    Science.gov (United States)

    Korczeniewska, Olga Anna; Khan, Junad; Tao, Yuanxiang; Eliav, Eli; Benoliel, Rafael

    2017-01-01

    To investigate the effects and interactions of sex and stress (provoked by chronic restraint [RS]) on pain-like behavior in a rat model of trigeminal neuropathic pain. The effects of sex and RS (carried out for 14 days as a model for stress) on somatosensory measures (reaction to pinprick, von Frey threshold) in a rat model of trigeminal neuropathic pain were examined. The study design was 2 × 4, with surgery (pain) and sham surgery (no pain) interacting with male restrained (RS) and unrestrained (nRS) rats and female RS and nRS rats. A total of 64 Sprague Dawley rats (32 males and 32 females) were used. Half of the animals in each sex group underwent RS, and the remaining half were left unstressed. Following the RS period, trigeminal neuropathic pain was induced by unilateral infraorbital nerve chronic constriction injury (IOCCI). Half of the animals in the RS group and half in the nRS group (both males and females) were exposed to IOCCI, and the remaining halves to sham surgery. Elevated plus maze (EPM) assessment and plasma interferon gamma (IFN-γ) levels were used to measure the effects of RS. Analysis of variance (ANOVA) was used to assess the effects of stress, sex, and their interactions on plasma IFN-γ levels, changes in body weight, EPM parameters, tactile allodynia, and mechanohyperalgesia. Pairwise comparisons were performed by using Tukey post hoc test corrected for multiple comparisons. Both male and female RS rats showed significantly altered exploratory behavior (as measured by EPM) and had significantly lower plasma IFN-γ levels than nRS rats. Rats exposed to RS gained weight significantly slower than the nRS rats, irrespective of sex. Following RS but before surgery, RS rats showed significant bilateral reductions in von Frey thresholds and significantly increased pinprick response difference scores compared to nRS rats, irrespective of sex. From 17 days postsurgery, RSIOCCI rats showed significantly reduced von Frey thresholds and

  15. Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

    Science.gov (United States)

    Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

    2017-12-06

    Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  16. Design and Efficacy of Nanogels Formulations for Intranasal Administration

    Directory of Open Access Journals (Sweden)

    Blessing A. Aderibigbe

    2018-05-01

    Full Text Available Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration.

  17. Trigeminal nociception-induced, cerebral Fos expression in the conscious rat

    NARCIS (Netherlands)

    Ter Horst, GJ; Meijler, WJ; Korf, J; Kemper, RHA

    2001-01-01

    Little is known about trigeminal nociception-induced cerebral activity and involvement of cerebral structures in pathogenesis of trigeminovascular headaches such as migraine. Neuroimaging has demonstrated cortical, hypothalamic and brainstem activation during the attack and after abolition with

  18. Immunogold localization of serotonin within synaptic terminals in the rat mesencephalic trigeminal nucleus

    NARCIS (Netherlands)

    Liem, RSB; Copray, JCVM

    1996-01-01

    With the use of postembedding electron-microscopic immunogold cytochemistry, the vesicular distribution of serotonin within serotonergic synaptic terminals in the mesencephalic trigeminal nucleus was determined in order to obtain further insight into the mechanisms and function, significance of

  19. Percutaneous micro-balloon compression for treatment of high risk idiopathic trigeminal neuralgia

    International Nuclear Information System (INIS)

    Zou Jianjun; Ma Yi; Wang Bin; Li Yanfeng; Huang Haitao; Li Fuyong

    2008-01-01

    Objective: To evaluate the clinical effectiveness and complications of percutaneous micro- balloon compression (PMC) of trigeminal ganglion for high risk idiopathic trigeminal neuralgia. Methods: To analyze retrospectively the clinical data of 3053 cases of idiopathic trigeminal nemalgia, of which 804 cases were in high risk, who underwent PMC from Jan. 2001 to Dec. 2007 in our department. Results: 833 procedures were performed on these 804 patients. The immediate effective rate was 97.3%; with recurrence rate of 6.8%, ipsilateral paresthesia incidence 3.7%; and no keratohelcosis with approximately 2/3 masticator, muscles weakness and diplopia 0.2%. Mean follow-up time was 36 months. Conclusions: PMC procedure is very effective for idiopathic trigeminal neuralgia especially in high risk patients, and especially prefer for the pain involved the first branch neuralgia. (authors)

  20. MRI and MR angiography of persistent trigeminal artery

    International Nuclear Information System (INIS)

    Piotin, M.; Miralbes, S.; Cattin, F.; Marchal, H.; Amor-Sahli, M.; Moulin, T.; Bonneville, J.F.

    1996-01-01

    We describe the MRA and MR angiography (MRA) features of persistent trigeminal artery (PTA) found incidentally in eight patients, with special attention to its origin, site and course. The different patterns of posterior communicating arteries were also noted. The PTA were shown on sagittal, coronal and axial MRI and on MRA. In four cases, the PTA arose from the lateral aspect of the intracavernous internal carotid artery, ran caudally, passing round the bottom of the dorsum sellae to join the basilar artery. In the other four cases, it arose from the medial aspect, ran caudally through the sella turcica and pierced the dorsum sellae to join the basilar artery. The posterior communicating arteries were present unilaterally in five cases and bilaterally in one, and absent bilaterally in two. Identification of a PTA with a trans-sellar course is crucial if a trans-sphenoidal surgery is planned. (orig.). With 3 figs

  1. Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

    Science.gov (United States)

    Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

    2017-12-01

    We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

  2. Ophthalmic branch radiofrequency thermocoagulation for atypical trigeminal neuralgia:a case report.

    Science.gov (United States)

    Du, Shibin; Ma, Xiaoliang; Li, Xiaoqin; Yuan, Hongjie

    2015-01-01

    Trigeminal neuralgia is an intense neuralgia involving facial areas supplied by trigeminal nerve. The pain is characterized by sudden onset, short persistence, sharp or lancinating. Trigeminal neuralgia commonly affects frontal areas, infraorbital or paranasal areas, mandibular areas and teeth. While Trigeminal neuralgia affecting merely the upper eyelid is rare. Here we report a case of atypical Trigeminal neuralgia confined to the upper eyelid. The patient was pain free during the follow-up period of 6 months after unusual ophthalmic branch radiofrequency thermocoagulation. A 55-year-old female patient was diagnosed as primary trigeminal neuralgia involving the right upper eyelid. As the pain could not be controlled by drug therapy, peripheral nerve branch radiofrequency thermocoagulation was recommended. A combination of infratrochlear, supratrochlear and lacrimal radiofrequency thermocoagulation was implemented in this case. The point where the bridge of the nose abuts the supraorbital ridge and the point slightly above the lateral canthus along outer border of the orbit were selected respectively as the puncture sites. After positive diagnostic test, radiofrequency thermocoagulation of the above-mentioned nerve branches was performed respectively. The patient was pain free immediately after the treatment and during the follow-up period of 6 months. Trigeminal neuralgia is a common severe and chronic facial neuralgia which requires accurate diagnosis and effective therapy. With typical clinical symptoms, normal neurological signs, normal CT and MRI findings, the patient was diagnosed as classic trigeminal neuralgia. As the patient was drug resistant, some invasive treatments were considered. Peripheral branch neurolysis was chosen for its minimal invasiveness, convenience, low risk and not affecting further invasive treatments. According to the anatomic data and the diagnostic test results, infratrochlear, supratrochlear and lacrimal nerve were responsible

  3. Advances in diagnosis and treatment of trigeminal neuralgia

    Science.gov (United States)

    Montano, Nicola; Conforti, Giulio; Di Bonaventura, Rina; Meglio, Mario; Fernandez, Eduardo; Papacci, Fabio

    2015-01-01

    Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN). Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression) and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures) have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that neurostimulation might represent an opportunity in TN refractory to other surgical treatments. The aim of this work was to review the recent literature about the pathogenesis, diagnosis, and medical and surgical treatments, and discuss the significant advances in all these fields

  4. Visualization of isolated trigeminal nerve invasion by lymphoma using gadolinium-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Manon-Espaillat, R.; Lanska, D.J.; Ruff, R.L.; Cleveland Veteran's Administration Medical Center, OH; Case Western Reserve Univ., Cleveland, OH; Masaryk, T.; University Hospitals of Cleveland, OH; Case Western Reserve Univ., Cleveland, OH

    1990-01-01

    A 50-year-old man with active histiocytic lymphoma for 12 years developed an isolated right trigeminal neuropathy. Initial evaluation with head computed tomography, X-rays of the skull base, bone scan, and cerebrospinal fluid analysis including cytology were normal. Gadolinium-enhanced magnetic resonance imaging (MRI) showed enlargement of the proximal third of the right trigeminal nerve. Gadolinium-enhanced MRI can be useful for the early demonstration of cranial nerve invasion by lymphoma. (orig.)

  5. Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Matthias Lübbert

    Full Text Available Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants, environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants. In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.

  6. NEURO-VASCULAR CONFLICT AS CAUSATIVE FACTOR IN IDI-OPATHIC TRIGEMINAL NEURALGIA

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    Mumtaz Ali

    2010-12-01

    Full Text Available Introduction Trigeminal neuralgia is one of the most unbearable pain syndromes in one or more branches of trigeminal nerve. The basic pathology is still poorly understood 1. Two divergent view points, central versus peripheral have been presented to explain the possible mechanism 2. In spite of numerous favorable reports, the neurovascular conflict theory remains contra-vertical 3. Nevertheless, whether or not, neurovascular compression is accessory or predominant in the mechanism of trigeminal neuralgia is not yet determined. Although neurovascular compression and global atrophy of the root, a focal arachnoid thickening and angulated root on crossing over the petrous ridge have been observed. Yet, neurovascular conflict has made responsible as the main cause of this neuralgia 4. This lead to focal demylination of the nerve due to its pulsatile compression. Demylination result in short circuiting of neuronal flow and hence trigeminal neuralgia 5.      Present study was therefore designed as to appreciate neurovascular conflict as causative agent in idiopathic trigeminal neuralgia. Material and Methods This prospective observational study was conducted in department of Neurosurgery Government Lady Reading Hospital Peshawar where microvascular decompression is performed as a primary procedure of choice for patients with trigeminal neuralgia. The duration of this study was from May 2003 – to June 2007. Total number of patients operated was 86. Drug resistant cases of trigeminal neuralgia that were   willing for operation was selected and proper clinical record was documented. MRI was done in all patients to exclude secondary causes of trigeminal Neuralgia. Under general Anesthesia in lateral position, small 2.5x2.5cm retro-mastoid craniotomy was performed. All these cases were operated by one surgeon with a team of associate’s doctors. Microscopic per-operative anatomical findings were recorded. Any possible per-operative complications

  7. Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro

    OpenAIRE

    Gulbransen, Brian D; Clapp, Tod R; Kinnamon, Sue C; Finger, Thomas E

    2008-01-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear (Finger et al. 2003). Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein α-gustducin, PLCβ2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve respo...

  8. Aberrant TRPV1 expression in heat hyperalgesia associated with trigeminal neuropathic pain.

    Science.gov (United States)

    Urano, Hiroko; Ara, Toshiaki; Fujinami, Yoshiaki; Hiraoka, B Yukihiro

    2012-01-01

    Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1) in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL) model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP) were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

  9. [Influence of trigeminal nerve lesion on facial growth: study of two cases of Goldenhar syndrome].

    Science.gov (United States)

    Darris, Pierre; Treil, Jacques; Marchal-Sixou, Christine; Baron, Pascal

    2015-06-01

    This cases report confirms the hypothesis that embryonic and maxillofacial growth are influenced by the peripheral nervous system, including the trigeminal nerve (V). So, it's interesting to use the stigma of the trigeminal nerve as landmarks to analyze the maxillofacial volume and understand its growth. The aim of this study is to evaluate the validity of the three-dimensional cephalometric analysis of Treil based on trigeminal landmarks. The first case is a caucasian female child with Goldenhar syndrome. The second case is a caucasian male adult affected by the same syndrome. In both cases, brain MRI showed an unilateral trigeminal nerve lesion, ipsilateral to the facial dysmorphia. The results of this radiological study tend to prove the primary role of the trigeminal nerve in craniofacial growth. These cases demonstrate the validity of the theory of Moss. They are one of anatomo-functional justifications of the three-dimensional cephalometric biometry of Treil based on trigeminal nerve landmarks. © EDP Sciences, SFODF, 2015.

  10. Multimodal Image-Based Virtual Reality Presurgical Simulation and Evaluation for Trigeminal Neuralgia and Hemifacial Spasm.

    Science.gov (United States)

    Yao, Shujing; Zhang, Jiashu; Zhao, Yining; Hou, Yuanzheng; Xu, Xinghua; Zhang, Zhizhong; Kikinis, Ron; Chen, Xiaolei

    2018-05-01

    To address the feasibility and predictive value of multimodal image-based virtual reality in detecting and assessing features of neurovascular confliction (NVC), particularly regarding the detection of offending vessels, degree of compression exerted on the nerve root, in patients who underwent microvascular decompression for nonlesional trigeminal neuralgia and hemifacial spasm (HFS). This prospective study includes 42 consecutive patients who underwent microvascular decompression for classic primary trigeminal neuralgia or HFS. All patients underwent preoperative 1.5-T magnetic resonance imaging (MRI) with T2-weighted three-dimensional (3D) sampling perfection with application-optimized contrasts by using different flip angle evolutions, 3D time-of-flight magnetic resonance angiography, and 3D T1-weighted gadolinium-enhanced sequences in combination, whereas 2 patients underwent extra experimental preoperative 7.0-T MRI scans with the same imaging protocol. Multimodal MRIs were then coregistered with open-source software 3D Slicer, followed by 3D image reconstruction to generate virtual reality (VR) images for detection of possible NVC in the cerebellopontine angle. Evaluations were performed by 2 reviewers and compared with the intraoperative findings. For detection of NVC, multimodal image-based VR sensitivity was 97.6% (40/41) and specificity was 100% (1/1). Compared with the intraoperative findings, the κ coefficients for predicting the offending vessel and the degree of compression were >0.75 (P < 0.001). The 7.0-T scans have a clearer view of vessels in the cerebellopontine angle, which may have significant impact on detection of small-caliber offending vessels with relatively slow flow speed in cases of HFS. Multimodal image-based VR using 3D sampling perfection with application-optimized contrasts by using different flip angle evolutions in combination with 3D time-of-flight magnetic resonance angiography sequences proved to be reliable in detecting NVC

  11. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

    Science.gov (United States)

    Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

    2013-07-15

    The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

  12. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

    Science.gov (United States)

    Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

    2006-08-24

    Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery

  13. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2006-08-01

    Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

  14. Evaluation of Intranasal Midazolam as an Anesthetic Premedication in Preschool Children

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    Sh Behdad

    2005-10-01

    Full Text Available Introduction: Preoperative psycho emotional preparation of patients is one of the principle purposes of anesthesia which can be achieved by administration of premedications. Children should receive premedication before entering the operating room due to their dependence on parents and the fear and anxiety of separation from parents. Different drugs are administered for this purpose, but considering children's sensitivity, it is wise to use the most effective and comfortable medication with least side effects. Midazolam is a rapid onset, short acting and water soluble benzodiazapine which can be administered by oral, intravenous, intramuscular, rectal or intranasal routes. The purpose of this study was to evaluate the result of intranasal midazolam administration (0.2 mg/kg as a premedication in children aged 2-6 years.( Min dose and enough time Methods: In this randomized prospective study, 100 children aged between 2-6 years old in class ASA 1 and candidates of surgery were divided into two groups; case and control. The control group received several nasal drops of normal saline, while the case group received 0.2 mg/kg nasal midazolam 20 minutes before anesthesia induction. Results: Twenty minutes after administration of the nasal drops, 14% in the control group and 68% in the case group were alert and calm. (P value=0.0 . Mask acceptance during induction of anesthesia in control and case group was 14%and 72%, respectively (P value >0.00 The recovery time in the case group was longer (P value >0.5, but no complications (nausea, vomiting, respiratory and cardiovascular problems were seen in either group. Conclusion: Nasal midazolam with its anxiolytic, tranquilizing effects and no respiratory or cardiovascular complications is a safe drug and being better than parenteral drugs is acceptable by children.

  15. Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts Sensibilização intranasal com antígenos de Blomia tropicalis induz respostas alérgicas em camundos caracterizadas pela elevada contagem de soro IgE antígeno-específico e não específico e de eosinófilos no sangue periférico

    Directory of Open Access Journals (Sweden)

    Fumiko Takeda

    2004-02-01

    Full Text Available In order to evaluate the potential allergenicity of Blomia tropicalis (Bt antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.Para avaliar a capacidade alergizante do antígeno da Blomia tropicalis (Bt a produção de IgE específica e não específica a antígeno Bt foi monitorada em camundongos BALB/c após exposição ao antígeno por via nasal. Foi evidenciado que Bt contem um alérgeno funcional em seus componentes. Os componentes alergênicos entretanto, quando administrados por via intra-nasal, sem qualquer adjuvante, não induzem resposta IgE durante um pequeno período. Por outro lado, a inocula

  16. Study of Preinduction Sedation with Intranasal Midazolam in Children

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    A. Rostaminejad

    2010-04-01

    Full Text Available Introduction & Objectives: Surgical procedures are the most stressful expreiences in life, specially in children. Different methods are used before operation to decrease the stress. Intranasal midazolam is an effective way of preparing before operation and to prevent the separation irritability.Materials & Methods: In a double blind experimental trial study , 60 patients aged 2-6 years with ASAI who had no elective surgery in the past were randomly chosen and divided into two groups.For the patients in group I intranasal midazolam 0.2 mg/kg was administerated and for the patients in group II the equal volume of normal saline was used. The patients’ crying was considered as mild, moderate, and severe. The irritability of their hands shaking during IV canula insertion,consciousness before the induction of anesthesia and cooperation during the mask ventilation were also evaluated.Results: The result of our study determined that 93.3% of the children in group I didn’t cry or they did mildly when separated from their parents but 90% of the children of group II cried moderately and some severely and 90% of the patients in group I cooperated well when separated from their parents. The resistance in group II was moderate or severe in 76.6%. Before induction of anesthesia 73.4% of group I were asleep but woke up with stimulation. 93.3% of the patients in group II were awake and irritated.90% of group I shook their hands steadily during iv cannula insertion but their hands shaking increased in 83.3% of group II..100% of group I cooperated well during face mask ventilation but 76.6% of group II did not. Conclusion: The above mentioned experiences showed that the intranasal midazolam is an effective way of preinduction sedation in children.

  17. Intranasal and sublingual delivery of inactivated polio vaccine.

    Science.gov (United States)

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  18. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  19. Advances in diagnosis and treatment of trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Montano N

    2015-02-01

    Full Text Available Nicola Montano,1 Giulio Conforti,1 Rina Di Bonaventura,1 Mario Meglio,2 Eduardo Fernandez,1 Fabio Papacci1 1Institute of Neurosurgery, Catholic University, Rome, 2Institute of Neurosurgery, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Abstract: Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN. Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that

  20. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    Science.gov (United States)

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  1. Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

    Science.gov (United States)

    Atkinson, M E; Shehab, S A

    1986-12-01

    In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

  2. The Molecular Fingerprint of Dorsal Root and Trigeminal Ganglion Neurons

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    Douglas M. Lopes

    2017-09-01

    Full Text Available The dorsal root ganglia (DRG and trigeminal ganglia (TG are clusters of cell bodies of highly specialized sensory neurons which are responsible for relaying information about our environment to the central nervous system. Despite previous efforts to characterize sensory neurons at the molecular level, it is still unknown whether those present in DRG and TG have distinct expression profiles and therefore a unique molecular fingerprint. To address this question, we isolated lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin-GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses showed that, despite being overwhelmingly similar, a number of genes are differentially expressed in DRG and TG neurons. Importantly, we identified 24 genes which were uniquely expressed in either ganglia, including an arginine vasopressin receptor and several homeobox genes, giving each population a distinct molecular fingerprint. We compared our findings with published studies to reveal that many genes previously reported to be present in neurons are in fact likely to originate from other cell types in the ganglia. Additionally, our neuron-specific results aligned well with a dataset examining whole human TG and DRG. We propose that the data can both improve our understanding of primary afferent biology and help contribute to the development of drug treatments and gene therapies which seek targets with unique or restricted expression patterns.

  3. Advanced MRI manifestations of trigeminal ganglioneuroma: a case report and literature review

    International Nuclear Information System (INIS)

    Deng, Xiaojuan; Fang, Jingqin; Luo, Qingya; Tong, Haipeng; Zhang, Weiguo

    2016-01-01

    Ganglioneuroma is a rare benign tumor originating from the sympathetic nerves, and its origination from the trigeminal nerves is even rarer. Only 4 cases of ganglioneuroma originating from the trigeminal nerve have previously been reported, and these studies only reported conventional MRI manifestations. To our knowledge, the advanced MRI features of trigeminal ganglioneuroma have not been reported thus far. This study reports a case of trigeminal ganglioneuroma in the left cerebellopontine angle. Advanced MRI showed the following tumor characteristics: significantly increased perfusion on perfusion imaging; isointense on diffusion-weighted imaging, whorled appearance within the tumor and no significant signs of damage to the white matter fiber tracts in the fractional anisotropy color map, and compare to the adjacent brain tissue, Choline didn’t show markedly elevation, and N-acetylaspartate peak showed slightly reduction on magnetic resonance spectroscopy. The tumor was completely resected, and the diagnosis of ganglioneuroma was confirmed by postoperative pathological examination. This case demonstrates the conventional as well as advanced MRI manifestations of this rare extra-axial tumor, which have never been previously reported. In addition, we reviewed the literature to demonstrate the advanced MRI features of trigeminal ganglioneuroma, in order to aid preoperative diagnosis and differentiation

  4. Phenytoin and carbamazepine in trigeminal neuralgia: marketing-based versus evidence-based treatment

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    Keppel Hesselink JM

    2017-07-01

    Full Text Available Jan M Keppel Hesselink,1 Michael E Schatman2,31Institute for Neuropathic Pain, Bosch en Duin, the Netherlands; 2Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 3Boston Pain Care, Waltham, MA, USAIntroductionMost review articles support carbamazepine as a first-line pharmacotherapy for idiopathic trigeminal neuralgia.1–3 However, the empirical support for this recommendation is somewhat suspect. Phenytoin, as the prototype for all anticonvulsants, was already positioned as an analgesic compound 70 years ago. Since these initial findings, the data that have been gathered have supported the use of anticonvulsants as painkillers – from phenytoin up to and including more recent anticonvulsants such as gabapentin and pregabalin. Since 1942, a number of papers supported phenytoin’s therapeutic effects in trigeminal neuralgia (Table 1. The introduction of carbamazepine in 1962 by Geigy shifted the interest of neurologists from phenytoin as a treatment for trigeminal neuralgia to carbamazepine, without sound scientific evidence. To date, no convincing randomized controlled trials (RCTs have been published supporting the role of carbamazepine in trigeminal neuralgia, and we could not identify a single study comparing the effects of phenytoin with those of carbamazepine. Accordingly, phenytoin should probably be considered more often as a viable therapy for (treatmentresistant trigeminal neuralgia.

  5. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

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    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

  6. Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior

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    Calcutt, Sarah E.; Burke, Kimberly; de Waal, Frans B. M.

    2017-01-01

    Oxytocin has been suggested as a treatment to promote positive social interactions in people with Autism Spectrum Disorders (ASD). However, it is difficult to test this effect outside of the laboratory in realistic social situations. One way to resolve this issue is to study behavioral changes in closely related species with complex social relationships, such as chimpanzees. Here, we use captive, socially housed chimpanzees to evaluate the effects of oxytocin in a socially complex environment. After administering intranasal oxytocin or a placebo to an individual chimpanzee (total n = 8), she was returned to her social group. An experimenter blind to the condition measured the subject's social behavior. We failed to find a behavioral difference between conditions. As one of the goals for oxytocin administration as a treatment for ASD is increasing prosocial behaviors during ‘real world’ encounters, it is problematic that we failed to detect behavioral changes in our closest living relatives. However, our null findings may be related to methodological challenges such as determining an effective dose of oxytocin for chimpanzees and how long oxytocin takes to cross the blood-brain barrier. Thus, more research on intranasal oxytocin dosing and uptake are needed to continue exploring whether oxytocin changes social behavior in naturalistic settings and as a treatment for ASD. PMID:28845444

  7. Sensory trigeminal ULF-TENS stimulation reduces HRV response to experimentally induced arithmetic stress: A randomized clinical trial.

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    Monaco, Annalisa; Cattaneo, Ruggero; Ortu, Eleonora; Constantinescu, Marian Vladimir; Pietropaoli, Davide

    2017-05-01

    Ultra Low Frequency Transcutaneous Electric Nervous Stimulation (ULF-TENS) is extensively used for pain relief and for the diagnosis and treatment of temporomandibular disorders (TMD). In addition to its local effects, ULF-TENS acts on the autonomic nervous system (ANS), with particular reference to the periaqueductal gray (PAG), promoting the release of endogenous opioids and modulating descending pain systems. It has been suggested that the PAG participates in the coupling between the emotional stimulus and the appropriate behavioral autonomic response. This function is successfully investigated by HRV. Therefore, our goal is to investigate the effects of trigeminal ULF-TENS stimulation on autonomic behavior in terms of HRV and respiratory parameters during an experimentally-induced arithmetic stress test in healthy subjects. Thirty healthy women between 25 and 35years of age were enrolled and randomly assigned to either the control (TENS stimulation off) or test group (TENS stimulation on). Heart (HR, LF, HF, LF/HF ratio, DET, RMSSD, PNN50, RR) and respiratory (BR) rate were evaluated under basal, T1 (TENS off/on), and stress (mathematical task) conditions. Results showed that HRV parameters and BR significantly changed during the arithmetic stress paradigm (pTENS and control group could be discriminated only by non-linear HRV data, namely RR and DET (p=0.038 and p=0.027, respectively). During the arithmetic task, LF/HF ratio was the most sensitive parameter to discriminate between groups (p=0.019). Our data suggest that trigeminal sensory ULF-TENS reduces the autonomic response in terms of HRV and BR during acute mental stress in healthy subjects. Future directions of our work aim at applying the HRV and BR analysis, with and without TENS stimulation, to individuals with dysfunctional ANS among those with TMD. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Increased Asics Expression via the Camkii-CREB Pathway in a Novel Mouse Model of Trigeminal Pain

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    Yan Wang

    2018-03-01

    Full Text Available Background/Aims: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. Methods: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. Results: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP in the periaqueductal grey matter. Interestingly, the acid-induced trigeminal pain behaviour was inhibited by amiloride, an antagonist of acid-sensing ion channels (ASICs, but not by AMG-9810, an inhibitor of transient receptor potential cation channel V1(TRPV1. In addition, the relative mRNA and protein expression levels of ASIC1a and ASIC3 were increased in the acid-induced trigeminal nociceptive pathways. Furthermore, blocking CaMKII with KN-93 significantly reduced the acid-induced trigeminal pain behaviour and c-FOS gene expression. Conclusion: The data suggested that chronic intermittent administration of an acidic solution to mice resulted in trigeminal hypersensitivity and that dural acid-induced trigeminal pain behaviour in mice may mechanistically mimic migraine. The observations here identify an entirely novel treatment strategy for migraine.

  9. Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

    Science.gov (United States)

    Dellweg, Dominic; Wenze, Markus; Hoehn, Ekkehard; Bourgund, Olaf; Haidl, Peter

    2013-08-01

    Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P humidification (P = .001, P humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

  10. The Association of Industry Payments to Physicians with Prescription of Brand-Name Intranasal Corticosteroids.

    Science.gov (United States)

    Morse, Elliot; Fujiwara, Rance J T; Mehra, Saral

    2018-06-01

    Objectives To examine the association of industry payments for brand-name intranasal corticosteroids with prescribing patterns. Study Design Cross-sectional retrospective analysis. Setting Nationwide. Subjects and Methods We identified physicians prescribing intranasal corticosteroids to Medicare beneficiaries 2014-2015 and physicians receiving payment for the brand-name intranasal corticosteroids Dymista and Nasonex. Prescription and payment data were linked by physician, and we compared the proportion of prescriptions written for brand-name intranasal corticosteroids in industry-compensated vs non-industry-compensated physicians. We associated the number and dollar amount of industry payments with the relative frequency of brand-name prescriptions. Results In total, 164,587 physicians prescribing intranasal corticosteroids were identified, including 7937 (5%) otolaryngologists; 10,800 and 3886 physicians received industry compensation for Dymista and Nasonex, respectively. Physicians receiving industry payment for Dymista prescribed more Dymista as a proportion of total intranasal corticosteroid prescriptions than noncompensated physicians (3.1% [SD = 9.6%] vs 0.2% [SD = 2.5%], respectively, P association was stronger in otolaryngologists than general practitioners ( P brand-name intranasal corticosteroids is significantly associated with prescribing patterns. The magnitude of association may depend on physician specialty and the drug's time on the market.

  11. Percutaneous high-frequency selective rhizotomy in the trigeminal neuralgia therapy in multiple sclerosis

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    V. M. Tyurnikov

    2012-01-01

    Full Text Available Trigeminal neuralgia is a rare symptom of multiple sclerosis affecting the disability. Multiple sclerosis related trigeminal neuralgia has been attributed to a demyelinating lesion in the pons. When the adequate pain drug-relieve therapy is not possible or when the patient becomes refractory to the treatment or can not continue pharmacological treatment because of the side effects, surgical intervention, including percutaneous radiofrequency rhizotomy is being discussed. Literature review and the data upon the efficiency and safety of this neurosurgical treatment in 16 patients with multiple sclerosis have been analyzed. Percutaneous radiofrequency rhizotomy has been proved to be a safe, reproducible and effective method of the symptomatic surgical treatment of trigeminal neuralgia in patients with multiple sclerosis in cases of the intolerance/inefficiency of the pharmacological therapy.

  12. Oxcarbazepine: Drug of the future in the treatment of trigeminal neuralgia

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    Revant H Chole

    2011-01-01

    Full Text Available Background: The aim of the study was to estimate the efficacy of oxcarbazepine in trigeminal neuralgia. Oxcarbazepine is a novel antiepilepfic drug, and its effect on trigeminal neuralgia has not been studied extensively previously. Materials and methods: Fifty-three patients with trigeminal neuralgia (34 men and 19 women took a mean dose of 600 mg of oxcarbazepine for a period of three weeks. Pain intensity was measured by using visual analog scale. Results: Of the 53 patients, 42 (79% were completely or well controlled by OXC, and nine (17% partially but acceptably controlled. Treatment with OXC was therefore satisfactory initially in 51 (96% of the patients. In seven of these patients, mild transient side effects occurred but did not necessitate cessation of treatment Conclusion: OXC appears to be an effective substitute for carbamazepine in those patients intolerant of this agent, or experiencing significant side effects.

  13. Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

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    Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J.Y.

    2011-01-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions. PMID:21712529

  14. Ultrasound-Guided Intervention for Treatment of Trigeminal Neuralgia: An Updated Review of Anatomy and Techniques

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    Abdallah El-Sayed Allam

    2018-01-01

    Full Text Available Orofacial myofascial pain is prevalent and most often results from entrapment of branches of the trigeminal nerves. It is challenging to inject branches of the trigeminal nerve, a large portion of which are shielded by the facial bones. Bony landmarks of the cranium serve as important guides for palpation-guided injections and can be delineated using ultrasound. Ultrasound also provides real-time images of the adjacent muscles and accompanying arteries and can be used to guide the needle to the target region. Most importantly, ultrasound guidance significantly reduces the risk of collateral injury to vital neurovascular structures. In this review, we aimed to summarize the regional anatomy and ultrasound-guided injection techniques for the trigeminal nerve and its branches, including the supraorbital, infraorbital, mental, auriculotemporal, maxillary, and mandibular nerves.

  15. Pseudocapsule formation after gamma knife radiosurgery for trigeminal neurinoma. Case report

    International Nuclear Information System (INIS)

    Akiyama, Takenori; Ikeda, Eiji; Kawase, Takeshi; Yoshida, Kazunari

    2005-01-01

    A 38-year-old female presented with a trigeminal neurinoma manifesting as left facial paresthesia. The diagnosis was based on magnetic resonance (MR) imaging findings. Gamma knife radiosurgery (GKR) was performed at another hospital at her request. Fifteen months after the GKR, follow-up MR imaging revealed tumor regrowth causing extensive compression of the brainstem, and cyst formation in the tumor. Her clinical symptoms including facial pain and diplopia had worsened, so she was referred to our affiliated hospital for microsurgery. The tumor was totally resected, but the left trigeminal nerve had to be sacrificed because of pseudocapsule formation which covered both the tumor and the trigeminal nerve fibers. The diplopia disappeared, but her facial pain deteriorated after the operation. GKR can induce fibrosis or degenerative change in nearby structures, which may complicate subsequent surgery. (author)

  16. Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study.

    Science.gov (United States)

    Schöpf, V; Kollndorfer, K; Pollak, M; Mueller, C A; Freiherr, J

    2015-12-01

    The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients. Ten patients with post-infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration. When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index. Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction.

  17. Effects of intranasal medicines on microcirculatory blood flow of nasal cavity

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    Svistunov A.A.

    2012-09-01

    Full Text Available The article describes the new method of assessment of microcirculatory blood perfusion and introduction of this method into the study of intranasal drugs effects on mucosal blood flow in the nasal cavity. The research work presents some different groups of drugs — decongestants, physical solutions for irrigation therapy and local corticosteroids. It has been revealed that intranasal decongestants have a significant effect on the intranasal blood flow, but their intake affects the mucosal membrane of the nasal cavity. Other drugs have not shown such negative effects and have not caused tachyphylaxis. Therefore these medicines may be recommended for more common use in ENT-practice.

  18. Use of Intranasal Naloxone by Basic Life Support Providers.

    Science.gov (United States)

    Weiner, Scott G; Mitchell, Patricia M; Temin, Elizabeth S; Langlois, Breanne K; Dyer, K Sophia

    2017-01-01

    Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or

  19. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

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    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

  20. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

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    Prisco L

    2011-08-01

    Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

  1. The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias.

    Science.gov (United States)

    Costa, Alfredo; Antonaci, Fabio; Ramusino, Matteo Cotta; Nappi, Giuseppe

    2015-01-01

    Trigeminal autonomic cephalalgias (TACs) are a group of primary headaches including cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). Another form, hemicrania continua (HC), is also included this group due to its clinical and pathophysiological similarities. CH is the most common of these syndromes, the others being infrequent in the general population. The pathophysiology of the TACs has been partly elucidated by a number of recent neuroimaging studies, which implicate brain regions associated with nociception (pain matrix). In addition, the hypothalamic activation observed in the course of TAC attacks and the observed efficacy of hypothalamic neurostimulation in CH patients suggest that the hypothalamus is another key structure. Hypothalamic activation may indeed be involved in attack initiation, but it may also lead to a condition of central facilitation underlying the recurrence of pain episodes. The TACs share many pathophysiological features, but are characterised by differences in attack duration and frequency, and to some extent treatment response. Although alternative strategies for the TACs, especially CH, are now emerging (such as neurostimulation techniques), this review focuses on the available pharmacological treatments complying with the most recent guidelines. We discuss the clinical efficacy and tolerability of the currently used drugs. Due to the low frequency of most TACs, few randomised controlled trials have been conducted. The therapies of choice in CH continue to be the triptans and oxygen for acute treatment, and verapamil and lithium for prevention, but promising results have recently been obtained with novel modes of administration of the triptans and other agents, and several other treatments are currently under study. Indomethacin is extremely effective in PH and HC, while antiepileptic drugs (especially lamotrigine) appear to be

  2. Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

    Science.gov (United States)

    Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

    2015-06-04

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Trigeminal pain and quantitative sensory testing in painful peripheral diabetic neuropathy.

    Science.gov (United States)

    Arap, Astrid; Siqueira, Silvia R D T; Silva, Claudomiro B; Teixeira, Manoel J; Siqueira, José T T

    2010-07-01

    To evaluate patients with Diabetes Mellitus type 2 and painful peripheral neuropathy in order to investigate oral complaints and facial somatosensory findings. Case-control study; 29 patients (12 women, mean age 57.86 yo) with Diabetes Mellitus type 2 and 31 age-gender-matched controls were evaluated with a standardized protocol for general characteristics, orofacial pain, research diagnostic criteria for temporomandibular disorders, visual analogue scale and McGill Pain questionnaire, and a systematic protocol of quantitative sensory testing for bilateral facial sensitivity at the areas innervated by the trigeminal branches, which included the thermal detection by ThermoSensi 2, tactile evaluation with vonFrey filaments, and superficial pain thresholds with a superficial algometer (Micromar). Statistical analysis was performed with Wilcoxon, chi-square, confidence intervals and Spearman (ppain was reported by 55.2% of patients, and the most common descriptor was fatigue (50%); 17.2% had burning mouth. Myofascial temporomandibular disorders were diagnosed in 9 (31%) patients. The study group showed higher sensory thresholds of pain at the right maxillary branch (p=0.017) but sensorial differences were not associated with pain (p=0.608). Glycemia and HbA(1c) were positively correlated with the quantitative sensory testing results of pain (ppain thresholds were correlated with higher glycemia and glycated hemoglobin (p=0.027 and p=0.026). There was a high prevalence of orofacial pain and burning mouth was the most common complaint. The association of loss of pain sensation and higher glycemia and glycated hemoglobin can be of clinical use for the follow-up of DM complications. 2010 Elsevier Ltd. All rights reserved.

  4. Formulation and kinetic modeling of curcumin loaded intranasal mucoadhesive microemulsion

    Directory of Open Access Journals (Sweden)

    B Mikesh Patel

    2012-01-01

    Full Text Available It is a challenge to develop the optimum dosage form of poorly water-soluble drugs and to target them due to limited bioavailability, intra and inter subject variability. In this investigation, mucoadhesive microemulsion of curcumin was developed by water titration method taking biocompatible components for intranasal delivery and was characterized. Nasal ciliotoxicity studies were carried out using excised sheep nasal mucosa. in vitro release studies of formulations and PDS were performed. Labrafil M 1944 CS based microemulsion was transparent, stable and nasal non-ciliotoxic having particle size 12.32±0.81nm (PdI=0.223 and from kinetic modeling, the release was found to be Fickian diffusion for mucoadhesive microemulsion.

  5. Intranasal corticosteroids topical characteristics: side effects, formulation, and volume.

    Science.gov (United States)

    Petty, David A; Blaiss, Michael S

    2013-01-01

    Guidelines from throughout the world recommend intranasal corticosteroids (INSs) as first-line treatment for most patients with moderate to severe allergic rhinitis. In general, limited comparative studies between different INSs have not indicated that one particular steroid moiety is more effective than another in controlling symptoms of allergic rhinitis. However, there are numerous formulations available with different ingredients that may influence a patient's adherence to treatment. This article looks at topical features with these agents, specifically, formulations, vehicles (aqueous vs aerosol), and side effects such as epistaxis and nasal septal perforation. Topical side effects are minimal with INSs with the exception of epistaxis. There are major differences in formulations, volumes, and vehicles between INSs, which could affect adherence. Physicians need to be aware of the different INS attributes to try to match patients' preferences in order to achieve better adherence and improve outcomes in sufferers of allergic rhinitis.

  6. Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

    NARCIS (Netherlands)

    Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

    Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

  7. Electrophysiological and Morphological Properties of α and γ Motoneurons in the Rat Trigeminal Motor Nucleus

    Directory of Open Access Journals (Sweden)

    Kayo Nishimura

    2018-01-01

    Full Text Available The muscle contraction during voluntary movement is regulated by activities of α- and γ-motoneurons (αMNs and γMNs, respectively. The tension of jaw-closing muscles can be finely tuned over a wide range. This excellent function is likely to be achieved by the specific populations of αMNs innervating jaw-closing muscles. Indeed, we have recently demonstrated that in the rat dorsolateral trigeminal motor nucleus (dl-TMN, the size distribution of αMNs was bimodal and the population of smaller αMNs showed a size distribution similar to that of γMNs, by immunohistochemically identifying αMNs and γMNs based on the expressions of estrogen-related receptor gamma (Err3 and neuronal DNA binding protein NeuN together with ChAT. This finding suggests the presence of αMNs as small as γMNs. However, differences in the electrophysiological membrane properties between αMNs and γMNs remain unknown also in the dl-TMN. Therefore, in the present study, we studied the electrophysiological membrane properties of MNs in the dl-TMN of infant rats at postnatal days 7–12 together with their morphological properties using whole-cell current-clamp recordings followed by immunohistochemical staining with an anti-NeuN and anti-ChAT antibodies. We found that the ChAT-positive and NeuN-positive αMNs were divided into two subclasses: the first one had a larger cell body and displayed a 4-aminopyridine (4-AP-sensitive current while the second one had a smaller cell body and displayed a less prominent 4-AP-sensitive current and a low-threshold spike, suitable for their orderly recruitment. We finally found that γMNs showing ChAT-positive and NeuN-negative immunoreactivities had smaller cell bodies and displayed an afterdepolarization mediated by flufenamate-sensitive cation current. It is suggested that these electrophysiological and morphological features of MNs in the dl-TMN are well correlated with the precise control of occlusion.

  8. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

    Science.gov (United States)

    Galinkin, J L; Fazi, L M; Cuy, R M; Chiavacci, R M; Kurth, C D; Shah, U K; Jacobs, I N; Watcha, M F

    2000-12-01

    Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during

  9. Percutaneous microsphere compression for the treatment of bilateral primary trigeminal neuralgia

    International Nuclear Information System (INIS)

    Li Yanfeng; Ma Yi; Huang Haitao; Zou Jianjun; Wang Bin; Li Fuyong; Wang Quancai

    2010-01-01

    Objective: To evaluate the clinical effectiveness of percutaneous microsphere compression (PMC) in treating bilateral primary trigeminal neuralgia and to discuss the optimal contralateral operation time after one side trigeminal neuralgia was treated with PMC. Methods: From Dec.2000 to Aug. 2009 PMC was performed in 74 patients with bilateral primary trigeminal neuralgia. The clinical data were retrospectively analyzed. Based on the pain-relieving degree the therapeutic effect was evaluated. Complete disappearance of pain was regarded as the criteria of a successful procedure. According to the recovery of mastication function of the operated side, the operation time for the contralateral side was decided. Results: A total of 145 PMC procedures were carried out in 74 patients,including three repeated operations in 3 cases due to recurrent pain after initial PMC. The postoperative instant effective rate was 96.5%. The recurrence rate was 2.1% during a mean follow-up period of 2.9 years (ranged 1-7 years). Of the 74 patients, bilateral PMC was accomplished in 68, and among them 57 patients received the contralateral operation within 1-3 months after the initial procedure was finished. Conclusion: Percutaneous microsphere compression is a quite effective treatment for bilateral primary trigeminal neuralgia. Usually, PMC for the contralateral side can be considered to perform in 1-3 months after the initial procedure. (authors)

  10. Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

    Science.gov (United States)

    Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F

    2015-12-17

    Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Magnetic resonance neurography in the management of peripheral trigeminal neuropathy: experience in a tertiary care centre

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    Cox, Brian; Chhabra, Avneesh [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Zuniga, John R. [UT Southwestern Medical Center, Department of Oral and Maxillofacial Surgery, Surgery, Neurology and Neurotherapeutics, Dallas, TX (United States); Panchal, Neeraj [University of Pennsylvania, Department of Oral Maxillofacial Surgery, Philadelphia, PA (United States); Cheng, Jonathan [UT Southwestern Medical Center, Department of Plastic Surgery, Dallas, TX (United States)

    2016-10-15

    This tertiary care experience examines the utility of magnetic resonance neurography (MRN) in the management of peripheral trigeminal neuropathies. Seventeen patients with clinically suspected peripheral trigeminal neuropathies (inferior alveolar nerve and lingual nerve) were imaged uniformly with 1.5-T examinations. MRN results were correlated with clinical and surgical findings in operated patients and the impact on clinical management was assessed. Clinical findings included pain (14/17), sensory changes (15/17), motor changes (2/17) and palpable masses (3/17). Inciting events included prior dental surgery (12/17), trauma (1/17) and idiopathic incidents (4/17). Non-affected side nerves and trigeminal nerves in the intracranial and skull base course were normal in all cases. Final diagnoses on affected sides were nerve inflammation (4/17), neuroma in continuity (2/17), LN transection (1/17), scar entrapment (3/17), infectious granuloma (1/17), low-grade injuries (3/17) and no abnormality (3/17). Associated submandibular gland and sublingual gland oedema-like changes were seen in 3/17 cases because of parasympathetic effects. Moderate-to-excellent MRN-surgical correlation was seen in operated (8/17) patients, and neuroma and nerve transection were prospectively identified in all cases. MRN is useful for the diagnostic work-up of suspected peripheral trigeminal neuropathy patients with significant impact on clinical management and moderate-to-excellent correlation with intra-operative findings. (orig.)

  12. Magnetic resonance neurography in the management of peripheral trigeminal neuropathy: experience in a tertiary care centre

    International Nuclear Information System (INIS)

    Cox, Brian; Chhabra, Avneesh; Zuniga, John R.; Panchal, Neeraj; Cheng, Jonathan

    2016-01-01

    This tertiary care experience examines the utility of magnetic resonance neurography (MRN) in the management of peripheral trigeminal neuropathies. Seventeen patients with clinically suspected peripheral trigeminal neuropathies (inferior alveolar nerve and lingual nerve) were imaged uniformly with 1.5-T examinations. MRN results were correlated with clinical and surgical findings in operated patients and the impact on clinical management was assessed. Clinical findings included pain (14/17), sensory changes (15/17), motor changes (2/17) and palpable masses (3/17). Inciting events included prior dental surgery (12/17), trauma (1/17) and idiopathic incidents (4/17). Non-affected side nerves and trigeminal nerves in the intracranial and skull base course were normal in all cases. Final diagnoses on affected sides were nerve inflammation (4/17), neuroma in continuity (2/17), LN transection (1/17), scar entrapment (3/17), infectious granuloma (1/17), low-grade injuries (3/17) and no abnormality (3/17). Associated submandibular gland and sublingual gland oedema-like changes were seen in 3/17 cases because of parasympathetic effects. Moderate-to-excellent MRN-surgical correlation was seen in operated (8/17) patients, and neuroma and nerve transection were prospectively identified in all cases. MRN is useful for the diagnostic work-up of suspected peripheral trigeminal neuropathy patients with significant impact on clinical management and moderate-to-excellent correlation with intra-operative findings. (orig.)

  13. New Insights in Trigeminal Anatomy: A Double Orofacial Tract for Nociceptive Input

    NARCIS (Netherlands)

    Henssen, D.J.H.A.; Kurt, E.; Kozicz, L.T.; Dongen, R.T.M. van; Bartels, R.H.M.A.; Cappellen van Walsum, A.M. van

    2016-01-01

    Orofacial pain in patients relies on the anatomical pathways that conduct nociceptive information, originating from the periphery towards the trigeminal sensory nucleus complex (TSNC) and finally, to the thalami and the somatosensorical cortical regions. The anatomy and function of the so-called

  14. Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro.

    Science.gov (United States)

    Gulbransen, Brian D; Clapp, Tod R; Finger, Thomas E; Kinnamon, Sue C

    2008-06-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear. Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein alpha-gustducin, PLCbeta2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca2+ ([Ca2+]i). GFP-positive cells respond with increased [Ca2+]i to the bitter receptor ligand denatonium and this response is blocked by the PLC inhibitor U73122. In addition, GFP+ cells respond to the neuromodulators adenosine 5'-triphosphate and acetylcholine but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system.

  15. PROJECTIONS OF THE PARVOCELLULAR RETICULAR-FORMATION TO THE CONTRALATERAL MESENCEPHALIC TRIGEMINAL NUCLEUS IN THE RAT

    NARCIS (Netherlands)

    MINKELS, RF; JUCH, PJW; TERHORST, GJ; VANWILLIGEN, JD

    1991-01-01

    Projections of the parvocellular reticular nucleus (PCRt) to the contralateral mesencephalic trigeminal nucleus (Me5) were studied in the rat with neurophysiological and neuroanatomical techniques. Three types of responses (classified by latencies) were recorded extracellularly in the Me5 area after

  16. An autoradiographic analysis of the development of the chick trigeminal ganglion

    International Nuclear Information System (INIS)

    Amico-Martel, A.D; Noden, D.M.

    1980-01-01

    The avian trigeminal ganglion, which is embryonically derived from the neural crest and epidermal placodes, consists of two topographically segregated classes of immature neurons, large and small, during the second week of incubation, and two neuronal cell types, dark and light, interspersed throughout the mature ganglion. In order to establish the times of terminal mitosis of trigeminal sensory neurons, embryos were treated with [ 3 H]thymidine during the first week of incubation and their ganglia fixed on embryonic day 11. The embryonically large, distal, placodal-derived neurons were generated between days 2 and 5, while the small, proximal, neural crest-derived neurons were formed mostly between days 4 and 7. By comparing the locations of labelled cells in ganglia treated with isotope but fixed on day 18 on incubation with their 11-day counterparts, it was shown that there are no morpho-genetic rearrangements of neurons during the final week of incubation. Thus, no unique relationship exists between the two neuron types in the mature ganglion and the two cell classes in the immature trigeminal. Therefore, both the light and the dark neurons in the mature trigeminal ganglion arise from neural crest as well as placodal primordia. (author)

  17. Trigeminal Schwannoma with intra- and extracranial portions - a case report and review of the literature

    International Nuclear Information System (INIS)

    Souza, Ricardo Pires de; Setubal, Roger; Florencio, Filipe Toledo; Gomes, Marcio Rogerio Alcala; Mayo, Suzete Varela; Leiro, Luis Carlos Filgueira; Soares, Aldemir Humberto

    1997-01-01

    The authors report a case of a 40-year-old male patient presenting a mandibular branch Schwannoma of the trigeminal nerve with intra-and extracranial portions. The radiologic, computed tomographic and magnetic resonance imaging findings are discussed and a review of the literature is presented. (author)

  18. Trigeminal neuralgia--a coherent cross-specialty management program.

    Science.gov (United States)

    Heinskou, Tone; Maarbjerg, Stine; Rochat, Per; Wolfram, Frauke; Jensen, Rigmor Højland; Bendtsen, Lars

    2015-01-01

    Optimal management of patients with classical trigeminal neuralgia (TN) requires specific treatment programs and close collaboration between medical, radiological and surgical specialties. Organization of such treatment programs has never been described before. With this paper we aim to describe the implementation and feasibility of an accelerated cross-speciality management program, to describe the collaboration between the involved specialties and to report the patient flow during the first 2 years after implementation. Finally, we aim to stimulate discussions about optimal management of TN. Based on collaboration between neurologists, neuroradiologists and neurosurgeons a standardized program for TN was implemented in May 2012 at the Danish Headache Center (DHC). First out-patient visit and subsequent 3.0 Tesla MRI scan was booked in an accelerated manner. The MRI scan was performed according to a special TN protocol developed for this program. Patients initially referred to neurosurgery were re-directed to DHC for pre-surgical evaluation of diagnosis and optimization of medical treatment. Follow-up was 2 years with fixed visits where medical treatment and indication for neurosurgery was continuously evaluated. Scientific data was collected in a structured and prospective manner. From May 2012 to April 2014, 130 patients entered the accelerated program. Waiting time for the first out-patient visit was 42 days. Ninety-four percent of the patients had a MRI performed according to the special protocol after a mean of 37 days. Within 2 years follow-up 35% of the patients were referred to neurosurgery after a median time of 65 days. Five scientific papers describing demographics, clinical characteristics and neuroanatomical abnormalities were published. The described cross-speciality management program proved to be feasible and to have acceptable waiting times for referral and highly specialized work-up of TN patients in a public tertiary referral centre for headache

  19. Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies.

    Science.gov (United States)

    Walum, Hasse; Waldman, Irwin D; Young, Larry J

    2016-02-01

    Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding, and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering, evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this article, we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, prestudy odds, and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus, the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Directory of Open Access Journals (Sweden)

    Rasmus Mortensen

    Full Text Available Streptococcus pyogenes (group A streptococcus, GAS is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  1. Amino acid specificity of fibers of the facial/trigeminal complex innervating the maxillary barbel in the Japanese sea catfish, Plotosus japonicus.

    Science.gov (United States)

    Caprio, John; Shimohara, Mami; Marui, Takayuki; Kohbara, Jun; Harada, Shuitsu; Kiyohara, Sadao

    2015-12-01

    The Japanese sea catfish, Plotosus japonicus, possesses taste and solitary chemoreceptor cells (SCCs) located on the external body surface that detect specific water-soluble substances. Here, we identify two major fiber types of the facial/trigeminal complex that transmit amino acid information to the medulla. Both single and few fiber preparations respond to amino acid stimulation in the 0.1 μM to mM range. One fiber type responds best to glycine and l-alanine (i.e. Gly/Ala fibers) whereas the other fiber type is best stimulated by l-proline and glycine betaine (hereafter referred to only as betaine) (i.e. Pro/Bet fibers). We demonstrate that betaine, which does not alter the pH of the seawater and therefore does not activate the animals' highly sensitive pH sensors (Caprio et al., Science 344:1154-1156, 2014), is sufficient to elicit appetitive food search behavior. We further show that the amino acid specificity of fibers of the facial/trigeminal complex in P. japonicus is different from that in Ariopsis felis (Michel and Caprio, J. Neurophysiol. 66:247-260, 1991; Michel et al., J. Comp. Physiol. A. 172:129-138, 1993), a representative member of the only other family (Ariidae) of extant marine catfishes. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. SU-E-T-669: Radiosurgery Failure for Trigeminal Neuralgia: A Study of Radiographic Spatial Fidelity

    Energy Technology Data Exchange (ETDEWEB)

    Howe, J [Associates In Medical Physics, Louisville, KY (United States); Spalding, A [Norton Cancer Institute, Louisville, Kentucky (United States)

    2015-06-15

    Purpose: Management of Trigeminal Neuralgia with radiosurgery is well established, but often met with limited success. Recent advancements in imaging afford improvements in target localization for radiosurgery. Methods: A Trigeminal Neuralgia radiosurgery specific protocol was established for MR enhancement of the trigeminal nerve using a CISS scan with slice spacing of 0.7mm. Computed Tomography simulation was performed using axial slices on a 40 slice CT with slice spacing of 0.6mm. These datasets were registered using a mutual information algorithm and localized in a stereotactic coordinate system. Image registration between the MR and CT was evaluated for each patient by a Medical Physicist to ensure accuracy. The dorsal root entry zone target was defined on the CISS MR by a Neurosurgeon and dose calculations performed on the localized CT. Treatment plans were reviewed and approved by a Radiation Oncologist and Neurosurgeon. Image guided radiosurgery was delivered using positioning tolerance of 0.5mm and 1°. Eight patients with Trigeminal Neuralgia were treated with this protocol. Results: Seven patients reported a favorable response to treatment with average Barrow Neurological Index pain score of four before treatment and one following treatment. Only one patient had a BNI>1 following treatment and review of the treatment plan revealed that the CISS MR was registered to the CT via a low resolution (5mm slice spacing) T2 MR. All other patients had CISS MR registered directly with the localized CT. This patient was retreated 6 months later using direct registration between CISS MR and localized CT and subsequently responded to treatment with a BNI of one. Conclusion: Frameless radiosurgery offers an effective solution to Trigeminal Neuralgia management provided appropriate technology and imaging protocols (utilizing submillimeter imaging) are established and maintained.

  3. SU-E-T-669: Radiosurgery Failure for Trigeminal Neuralgia: A Study of Radiographic Spatial Fidelity

    International Nuclear Information System (INIS)

    Howe, J; Spalding, A

    2015-01-01

    Purpose: Management of Trigeminal Neuralgia with radiosurgery is well established, but often met with limited success. Recent advancements in imaging afford improvements in target localization for radiosurgery. Methods: A Trigeminal Neuralgia radiosurgery specific protocol was established for MR enhancement of the trigeminal nerve using a CISS scan with slice spacing of 0.7mm. Computed Tomography simulation was performed using axial slices on a 40 slice CT with slice spacing of 0.6mm. These datasets were registered using a mutual information algorithm and localized in a stereotactic coordinate system. Image registration between the MR and CT was evaluated for each patient by a Medical Physicist to ensure accuracy. The dorsal root entry zone target was defined on the CISS MR by a Neurosurgeon and dose calculations performed on the localized CT. Treatment plans were reviewed and approved by a Radiation Oncologist and Neurosurgeon. Image guided radiosurgery was delivered using positioning tolerance of 0.5mm and 1°. Eight patients with Trigeminal Neuralgia were treated with this protocol. Results: Seven patients reported a favorable response to treatment with average Barrow Neurological Index pain score of four before treatment and one following treatment. Only one patient had a BNI>1 following treatment and review of the treatment plan revealed that the CISS MR was registered to the CT via a low resolution (5mm slice spacing) T2 MR. All other patients had CISS MR registered directly with the localized CT. This patient was retreated 6 months later using direct registration between CISS MR and localized CT and subsequently responded to treatment with a BNI of one. Conclusion: Frameless radiosurgery offers an effective solution to Trigeminal Neuralgia management provided appropriate technology and imaging protocols (utilizing submillimeter imaging) are established and maintained

  4. Long-Term Results for Trigeminal Schwannomas Treated With Gamma Knife Surgery

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    Hasegawa, Toshinori, E-mail: h-toshi@komakihp.gr.jp; Kato, Takenori; Iizuka, Hiroshi; Kida, Yoshihisa

    2013-12-01

    Purpose: Surgical resection is considered the desirable curative treatment for trigeminal schwannomas. However, complete resection without any complications remains challenging. During the last several decades, stereotactic radiosurgery (SRS) has emerged as a minimally invasive treatment modality. Information regarding long-term outcomes of SRS for patients harboring trigeminal schwannomas is limited because of the rarity of this tumor. The aim of this study was to evaluate long-term tumor control and functional outcomes in patients harboring trigeminal schwannomas treated with SRS, specifically with gamma knife surgery (GKS). Methods and Materials: Fifty-three patients harboring trigeminal schwannomas treated with GKS were evaluated. Of these, 2 patients (4%) had partial irradiation of the tumor, and 34 patients (64%) underwent GKS as the initial treatment. The median tumor volume was 6.0 cm{sup 3}. The median maximum and marginal doses were 28 Gy and 14 Gy, respectively. Results: The median follow-up period was 98 months. On the last follow-up image, 7 patients (13%) had tumor enlargement, including the 2 patients who had partial treatment. Excluding the 2 patients who had partial treatment, the actuarial 5- and 10-year progression-free survival (PFS) rates were 90% and 82%, respectively. Patients with tumors compressing the brainstem with deviation of the fourth ventricle had significantly lower PFS rates. If those patients with tumors compressing the brainstem with deviation of the fourth ventricle are excluded, the actuarial 5- and 10-year PFS rates increased to 95% and 90%, respectively. Ten percent of patients had worsened facial numbness or pain in spite of no tumor progression, indicating adverse radiation effect. Conclusions: GKS can be an acceptable alternative to surgical resection in patients with trigeminal schwannomas. However, large tumors that compress the brainstem with deviation of the fourth ventricle should be surgically removed first and then

  5. A RARE CASE OF PERSISTENT TRIGEMINAL ARTERY IN AN ADULT FEMALE WITH PARA POSTERIOR COMMUNICATING ARTERY ANEURYSM

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    Banavathu Daya Bharath Singh

    2015-05-01

    Full Text Available Anastomosis found in the adulthood between the carotid and vertebro - basilar systems, apart from the posterior communicating artery, are extremely infrequent and are due to the persistence of vessels that joined both systems during the fetal period. This carotid - vertebrobasilar anastomosis are the trigeminal, otic, and hypoglossal and proatlantal arteries. P ersistent trigeminal artery is the commonest of the above mentioned four arteries. The reported incidence is about 0.2%. Patients may be asymptomatic or present symptoms due to low flow of posterior circulation or carotid microembolization from posterior circulation. PTA can cause trigemina l neuralgia. We report in this paper a case of a persistant trigeminal artery found in an adult female with a para p com aneurysm who had persistent trigeminal artery which was seen in C T angiogram .

  6. Intranasal melanoma treated with radiation therapy in three dogs.

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    Davies, Owen; Spencer, Sarah; Necova, Slavomira; Holmes, Emma; Taylor, Angela; Blackwood, Laura; Lara-Garcia, Ana

    2017-12-01

    Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.

  7. Intranasal oxytocin modulates neural functional connectivity during human social interaction.

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    Rilling, James K; Chen, Xiangchuan; Chen, Xu; Haroon, Ebrahim

    2018-02-10

    Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals. © 2018 Wiley Periodicals, Inc.

  8. Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

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    Putcha, L.; Lei, Wu.; S-L Chow, Diana

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at Pgender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose of 0.4 mg or higher.

  9. Development and evaluation of nitrendipine nanoemulsion for intranasal delivery.

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    Jain, Ratnesh; Patravale, Vandana B

    2009-02-01

    The clinical efficacy of Nitrendipine (NDP), a potent antihypertensive molecule, is limited due to its low oral bioavailability (10% to 20%) resulting from its extensive first-pass metabolism. The purpose of the present investigation was to enhance the bioavailability of NDP through formulating a nanoemulsion for its intranasal delivery. A Caproyl 90 based nanoemulsion sytem with Tween 80 as the surfactant, Transcutol P and Solutol HS-15 as solubiliser and cosurfactant respectively, was developed. A single isotropic region, which is considered as a bicontinuous nanoemulsion, was identified in the pseudo-ternary phase diagrams developed at various Tween 80: Transcutol P: Solutol HS-15 ratios. NDP was solubilized in a system consisting of Tween 80: Transcutol P: Solutol HS-15 at 1:2:1 weight ratio. The developed nanoemulsion was safe for nasal administration as confirmed by nasal histopathlogy studies with the mean globule size of 98.50 nm. The drug content per actuation was found to be 99.58 +/- 0.05%, with no significant changes over a period of one month. In vivo absorption studies revealed that NDP absorption from the nanoemulsion had a rapid onset of action and a relative bioavailability of 60.44%, significantly greater than the marketed oral tablets.

  10. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

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    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  11. Intranasal epidermal growth factor treatment rescues neonatal brain injury

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    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  12. Microvascular Decompression for Classical Trigeminal Neuralgia Caused by Venous Compression: Novel Anatomic Classifications and Surgical Strategy.

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    Wu, Min; Fu, Xianming; Ji, Ying; Ding, Wanhai; Deng, Dali; Wang, Yehan; Jiang, Xiaofeng; Niu, Chaoshi

    2018-05-01

    Microvascular decompression of the trigeminal nerve is the most effective treatment for trigeminal neuralgia. However, when encountering classical trigeminal neuralgia caused by venous compression, the procedure becomes much more difficult, and failure or recurrence because of incomplete decompression may become frequent. This study aimed to investigate the anatomic variation of the culprit veins and discuss the surgical strategy for different types. We performed a retrospective analysis of 64 consecutive cases in whom veins were considered as responsible vessels alone or combined with other adjacent arteries. The study classified culprit veins according to operative anatomy and designed personalized approaches and decompression management according to different forms of compressive veins. Curative effects were assessed by the Barrow Neurological Institute (BNI) pain intensity score and BNI facial numbness score. The most commonly encountered veins were the superior petrosal venous complex (SPVC), which was artificially divided into 4 types according to both venous tributary distribution and empty point site. We synthetically considered these factors and selected an approach to expose the trigeminal root entry zone, including the suprafloccular transhorizontal fissure approach and infratentorial supracerebellar approach. The methods of decompression consist of interposing and transposing by using Teflon, and sometimes with the aid of medical adhesive. Nerve combing (NC) of the trigeminal root was conducted in situations of extremely difficult neurovascular compression, instead of sacrificing veins. Pain completely disappeared in 51 patients, and the excellent outcome rate was 79.7%. There were 13 patients with pain relief treated with reoperation. Postoperative complications included 10 cases of facial numbness, 1 case of intracranial infection, and 1 case of high-frequency hearing loss. The accuracy recognition of anatomic variation of the SPVC is crucial for the

  13. Keyhole craniotomy through retrosigmoid approach followed by microvascular decompression for primary trigeminal neuralgia:a report of 23 cases

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    Gang-ge CHENG

    2011-03-01

    Full Text Available Objective To explore the surgical technique,effects,and complications of keyhole craniotomy through retrosigmoid approach followed by microvascular decompression for primary trigeminal neuralgia.Methods The craniotomy with a keyhole incision above postauricular hairline followed by microvascular decompression was performed in 23 patients with primary trigeminal neuralgia.Dissection of intracranial part of trigeminal nerve under microscope was done to search for the offending vessels,which were thereby freed and between which and the root entry zone(REZ of trigeminal nerve the Teflon grafts were placed.Effects and complications were observed in follow-up,ranging from 1 month to 2 years.Results Out of 23 patients who were all found compression in REZ of trigeminal nerves by the offending vessels in operation,disappearance of symptoms post-surgery was found in 22 cases,face numbness on the surgical side in 3 cases and no effects in 1 case.Recurrence of pain was not observed in patients who had initially benefited from the surgery at the follow-up.Conclusion The keyhole craniotomy through retrosigmoid approach followed by microvascular decompression is safe and effective for primary trigeminal neuralgia,in which accurate technique during operation plays a vital role in the decrease of complications and the outcome post-surgery.

  14. Intercellular signal communication among odontoblasts and trigeminal ganglion neurons via glutamate.

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    Nishiyama, A; Sato, M; Kimura, M; Katakura, A; Tazaki, M; Shibukawa, Y

    2016-11-01

    Various stimuli to the exposed surface of dentin induce changes in the hydrodynamic force inside the dentinal tubules resulting in dentinal pain. Recent evidences indicate that mechano-sensor channels, such as the transient receptor potential channels, in odontoblasts receive these hydrodynamic forces and trigger the release of ATP to the pulpal neurons, to generate dentinal pain. A recent study, however, has shown that odontoblasts also express glutamate receptors (GluRs). This implies that cells in the dental pulp tissue have the ability to release glutamate, which acts as a functional intercellular mediator to establish inter-odontoblast and odontoblast-trigeminal ganglion (TG) neuron signal communication. To investigate the intercellular signal communication, we applied mechanical stimulation to odontoblasts and measured the intracellular free Ca 2+ concentration ([Ca 2+ ] i ). During mechanical stimulation in the presence of extracellular Ca 2+ , we observed a transient [Ca 2+ ] i increase not only in single stimulated odontoblasts, but also in adjacent odontoblasts. We could not observe these responses in the absence of extracellular Ca 2+ . [Ca 2+ ] i increases in the neighboring odontoblasts during mechanical stimulation of single odontoblasts were inhibited by antagonists of metabotropic glutamate receptors (mGluRs) as well as glutamate-permeable anion channels. In the odontoblast-TG neuron coculture, we observed an increase in [Ca 2+ ] i in the stimulated odontoblasts and TG neurons, in response to direct mechanical stimulation of single odontoblasts. These [Ca 2+ ] i increases in the neighboring TG neurons were inhibited by antagonists for mGluRs. The [Ca 2+ ] i increases in the stimulated odontoblasts were also inhibited by mGluRs antagonists. We further confirmed that the odontoblasts express group I, II, and III mGluRs. However, we could not record any currents evoked from odontoblasts near the mechanically stimulated odontoblast, with or without

  15. Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.

    Science.gov (United States)

    Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-01-10

    Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

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    Vineel Muppidi

    2017-06-01

    Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

  17. [Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

    Science.gov (United States)

    Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

    2014-10-01

    Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  18. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

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    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy.

    Science.gov (United States)

    Kurdoglu, Mertihan; Yildirim, Mulazim; Kurdoglu, Zehra; Erdem, Ahmet; Erdem, Mehmet; Bilgihan, Ayse; Goktas, Bulent

    2011-08-01

    To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk. The study was conducted with 44 voluntary postmenopausal women. In group I (n = 15), the patients were treated with only intranasal estradiol (300 μg/day estradiol hemihydrate). In group II (n = 11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment. Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p > 0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p < 0.05). Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.

  20. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

    Science.gov (United States)

    Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

    2017-09-01

    Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

  1. Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

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    "Bagher Larijani

    2005-07-01

    Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

  2. Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

    2018-05-16

    Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

    Science.gov (United States)

    Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

    To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

  4. Small Radiation Beam Dosimetry for Radiosurgery of Trigeminal Neuralgia: One Case Analysis

    International Nuclear Information System (INIS)

    Garcia-Garduno, O. A.; Larraga-Gutierrez, J. M.; Rodriguez-Villafuerte, M.; Martinez-Davalos, A.; Moreno-Jimenez, S.; Suarez-Campos, J. J.; Celis, M. A.

    2008-01-01

    The use of small radiation beams for trigeminal neuralgia (TN) treatment requires high precision and accuracy in dose distribution calculations and delivery. Special attention must be kept on the type of detector to be used. In this work, the use of GafChromic EBT registered radiochromic and X-OMAT V2 radiographic films for small radiation beam characterization is reported. The dosimetric information provided by the films (total output factors, tissue maximum ratios and off axis ratios) is compared against measurements with a shielded solid state (diode) reference detector. The film dosimetry was used for dose distribution calculations for the treatment of trigeminal neuralgia radiosurgery. Comparison of the isodose curves shows that the dosimetry produced with the X-OMAT radiographic film overestimates the dose distributions in the penumbra region

  5. Expression of inducible nitric oxide synthase in trigeminal ganglion cells during culture

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Zhou, MingFang; Zinck, Tina Jovanovic

    2005-01-01

    RNA and protein could be detected. The data suggest that iNOS expression may be a molecular mechanism mediating the adaptive response of trigeminal ganglia cells to the serum free stressful stimulus the culture environment provides. It may act as a cellular signalling molecule that is expressed after cell......Nitric oxide (NO) is an important signalling molecule that has been suggested to be a key molecule for induction and maintenance of migraine attacks based on clinical studies, animal experimental studies and the expression of nitric oxide synthase (NOS) immunoreactivity within the trigeminovascular......, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. In trigeminal ganglia cells not subjected to culture, endothelial (e) and neuronal (n) but not inducible (i) NOS mRNA and protein were detected. Culture of rat neurones resulted in a rapid axonal outgrowth of NOS positive...

  6. Selective percutaneous radiofrequency thermocoagulation in the treatment of trigeminal neuralgia:report on 1860 cases

    Institute of Scientific and Technical Information of China (English)

    吴承远; 孟凡刚; 徐淑军; 刘玉光; 王宏伟

    2004-01-01

    @@Trigeminal neuralgia (TN) is defined by the International Association for the Study of Pain as "a sudden, usually unilateral, severe, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve".1 The incidence rate is about three to five cases per year per 100000 persons and increases with age.2 In our hospital, percutaneous radiofrequency therapy was performed on 1860 patients with TN from June 1986 to April 2003, and percutaneous trigeminal ganglion radiofrequency therapy on 579 cases. Among this group of patients, X-ray, 3-D CT, and navigational localization of the oval foramen were performed on 42 cases. The indications, techniques, and results are reported here.

  7. Clinical experience with Leksell gamma knife in the treatment of trigeminal schwannomas

    Institute of Scientific and Technical Information of China (English)

    WANG En-min; PAN Li; ZHANG Nan; ZHOU Liang-fu; WANG Bing-jiang; DONG Ya-fei; DAI Jia-zhong; CAI Pei-wu

    2005-01-01

    @@ Trigeminal nerve schwannomas, which are rare, slowly growing, benign tumors, account for 0.2% to 1.0% of all intracranial tumors and 0.8% to 8.0% of intracranial schwannomas.1-5 These tumors are treated surgically.1-4 The development of microsurgery and skull base surgery has made complete resection possible in most patients. Nevertheless, cranial nerve sequelae appear after complete resection of these tumors because they are located close to the cavernous sinus and usually adhere to the vital vascular and neural structures. As an alternative to microsurgical resection, Leksell gamma knife (LGK) radiosurgery has been performed for patients with intracranial schwannomas to minimize the treatment-related morbidity and achieve a long-term control of tumor growth.6,7 In this report, we describe our 6-year experience in the treatment of 38 patients with trigeminal schwannomas by LGK.

  8. Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats.

    Science.gov (United States)

    Yoon, Jeong-Ho; Son, Jo-Young; Kim, Min-Ji; Kang, Song-Hee; Ju, Jin-Sook; Bae, Yong-Chul; Ahn, Dong-Kuk

    2018-05-01

    The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

  9. Oxcarbazepine: a new drug in the management of intractable trigeminal neuralgia.

    OpenAIRE

    Zakrzewska, J M; Patsalos, P N

    1989-01-01

    The efficacy and tolerability of oxcarbazepine, a keto derivative of carbamazepine, has been assessed in six patients (two males, four females; mean age 61 years, range 42-77), with trigeminal neuralgia refractory to carbamazepine therapy, over a period of 6 months. An excellent therapeutic response to oxcarbazepine was seen in all patients with pain control correlating well with serum drug concentrations of oxcarbazepine and its primary active metabolite 10-OH-carbazepine. Onset of the effec...

  10. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

    OpenAIRE

    Arvind Chaturvedi; H H Dash

    2011-01-01

    Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and...

  11. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

    Directory of Open Access Journals (Sweden)

    Khaled Abdallah

    Full Text Available Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG, into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project. These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

  12. PERCUTANEOUS BALLOON COMPRESSION OF GASSERIAN GANGLION FOR THE TREATMENT OF TRIGEMINAL NEURALGIA: AN EXPERIENCE FROM INDIA.

    Science.gov (United States)

    Agarwal, Anurag; Dhama, Vipin; Manik, Yogesh K; Upadhyaya, M K; Singh, C S; Rastogi, V

    2015-02-01

    Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve. Percutaneous balloon compression (PBC) of Gasserian ganglion is an effective, comparatively cheaper and simple therapeutic modality for treatment of TN. Compression secondary to PBC selectively injures the large myelinated A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, which carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off the trigger to the neuropathic trigeminal pain. In this current case series, we are sharing our experience with PBC of Gasserian Ganglion for the treatment of idiopathic TN in our patients at an academic university-based medical institution in India. During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in eleven patients suffering from idiopathic TN. There were nine female patients and two male patients with the age range of 35-70 years (median age: 54 years). In all patients cannulation of foramen ovale was done successfully in the first attempt. In eight out of eleven (72.7%) patients ideal 'Pear-shaped' balloon visualization could be achieved. In the remaining three patients (27.3%), inflated balloon was 'Bullet-shaped'. In one patient final placement of Fogarty balloon was not satisfactory and it ruptured during inflation. This case was deferred for one week when it was completed successfully with 'Pear-shaped' balloon inflation. During the follow up period of 1-13 months, there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off medicines (carbamazepine and baclofen) and other two patients are stable on very low doses of carbamazepine. All patients have reported marked improvement in quality of life. This case series shows that percutaneous balloon compression is a useful minimally invasive intervention for the

  13. Description of a neural sheath tumor of the trigeminal nerve: immunohistochemical and electron microscopy study

    OpenAIRE

    Khademi, Bijan; Owji, Seied Mohammad; Khosh, Khadije Jamshidi; Mohammadianpanah, Mohammad; Gandomi, Behrooz

    2006-01-01

    CONTEXT: Malignant neural sheath tumors of the trigeminal nerve affecting the nasal cavity and the paranasal sinuses are extremely rare. With conventional optical microscopy, their identification is difficult, and it is necessary to confirm them by means of electron microscopy and immunohistochemical techniques. CASE REPORT: The patient was a 41-year-old woman with a ten-month progressive history of pain followed by painful edema in the left facial region, and with symptoms of bleeding, secre...

  14. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    OpenAIRE

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    Yanping Wang,1,2 Xiaoling Zhang,2 Qiaobing Guan,2 Lihong Wan,2 Yahui Yi,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 2Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, Zhejiang Province, People’s Republic of China Abstract: The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural ...

  15. Differential regulation of glutamate receptors in trigeminal ganglia following masseter inflammation

    OpenAIRE

    Lee, Jongseok; Ro, Jin Y.

    2007-01-01

    The present study examined whether N-methyl-D-aspartate receptor (NMDAR) and 5-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits and group I metabotropic glutamate receptors (mGluRs) are constitutively expressed in trigeminal ganglia (TG) using Western blot analysis in male Sprague Dawley rats. We then investigated whether experimental induction of masseter inflammation influences glutamate receptor expressions by comparing the protein levels from naïve rats to th...

  16. Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review

    NARCIS (Netherlands)

    Siemerink, Martin J.; Freling, Nicole J. M.; Saeed, Peerooz

    2017-01-01

    Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and

  17. Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Lisa A Parr

    2014-09-01

    Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

  18. Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update

    Directory of Open Access Journals (Sweden)

    Mohammad Khan

    2017-01-01

    Full Text Available Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome.

  19. Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract☆

    Science.gov (United States)

    Abbey, Marcie J.; Patil, Vinit V.; Vause, Carrie V.; Durham, Paul L.

    2008-01-01

    Ethnopharmacological relevance Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. Aim of the study To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. Results Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24 h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. Conclusions Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation. PMID:17997062

  20. Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract.

    Science.gov (United States)

    Abbey, Marcie J; Patil, Vinit V; Vause, Carrie V; Durham, Paul L

    2008-01-17

    Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation.

  1. [Trigeminal motor paralysis and dislocation of the temporo-mandibular joints].

    Science.gov (United States)

    Ohkawa, S; Yoshida, T; Ohsumi, Y; Tabuchi, M

    1996-07-01

    A 64-year-old woman with diabetes mellitus was admitted to our hospital with left hemiparesis of sudden onset. A brain MRI demonstrated a cerebral infarction in the ventral part of the right lower pons. When left hemiparesis worsened, she had dislocation of the temporo-mandibular joints repeatedly. Then, her lower jaw deviated to the right when she opened her mouth. Also, there was decreased contraction of the right masseter when she clenched her teeth. These findings suggest that there was trigeminal motor paralysis on the right side resulting from involvement of the intrapontine trigeminal motor nerve. She has no history of dislocation of the temporo-mandibular joints. An X-ray film showed that the temporo-mandibular joints were intact. Thus, it is possible that deviation of the lower jaw was the cause of this dislocation. We suspect that dislocation of the temporo-mandibular joints may occur as a complication of unilateral trigeminal motor paralysis. This has not been reported to our knowledge.

  2. Surgical Management of Familial Trigeminal Neuralgia With Different Inheritance Patterns: A Case Report

    Directory of Open Access Journals (Sweden)

    Claudia Cervera-Martinez

    2018-05-01

    Full Text Available IntroductionTrigeminal neuralgia is a disorder characterized by unilateral electric shock-like pain, distributed in one or more trigeminal nerve branches and triggered by usually innocuous stimuli. Among the few case reports and literature reviews on familial trigeminal neuralgia (FTN, the results of several suggest the involvement of genes associated with biochemical alterations or atherosclerotic vascular malformations.BackgroundWe present four cases of FTN within two families (family A: two brothers; family B: two sisters. All patients were submitted to surgical treatment by the same surgeon.DiscussionCases 1 and 2 (family A exhibited FTN with an uncommon autosomal recessive pattern and clinical features consistent with previous literature reviews and case reports. However, in cases 3 and 4 (family B, we found FTN with a dominant autosomal pattern and an unusual physiopathology characterized by arachnoid adhesions.ConclusionWe conclude, in this case report, that there are several inheritance patterns as well as physiopathology that may be involved in FTN, and that both patterns described in our reported cases were successfully managed with surgery.

  3. Management of uncommon secondary trigeminal neuralgia related to a rare Arnold Chiari type I malformation

    Directory of Open Access Journals (Sweden)

    Zafar Ali Khan

    2017-12-01

    Full Text Available Background Trigeminal neuralgia (TN may sometimes present secondary to an intra-cranial cause. Arnold Chiari Malformation (ACM is downward herniation of the cerebellar tonsils through the foramen magnum that may be a cause of TN like pain in very rare cases. Aims The aim of this brief report is to suggest the proper management of uncommon secondary trigeminal neuralgia related to a rare Arnold Chiari type I malformation. Methods A male patient presented electric shock like stabbing pain on the right side of the face for more than ten years. The symptoms were typical of trigeminal neuralgia except that there was loss of corneal reflex on the right side and the patient also complained of gait & sleep disturbances. Complex and multilevel diagnosis was made. Results A multiplanar imaging through brain acquiring T1/T2W1 revealed ACM Type I Malformation with caudal displacement of cerebellar tonsils through foramen magnum. Conclusion Dental surgeons and oral and Maxillofacial Surgeons should exclude intra-cranial causes by Magnetic Resonance Imaging(MRI in patients of TN presenting with loss of corneal reflex, gait and sleep disturbances due to night time pain episodes.

  4. Relationship between Sensory Stimulation and Side Effects in Percutaneous Radiofrequency Treatment of the Trigeminal Ganglion.

    Science.gov (United States)

    Koning, Mark V; Koning, Nick J; Koning, Henk M; van Kleef, Maarten

    2014-09-01

    The objective of this study was to determine the efficacy of percutaneous radiofrequency (RF) treatment of the trigeminal ganglion for treating patients with trigeminal neuralgia, to determine which patients have a long-term benefit, and to evaluate the effect of RF parameters. A retrospective study in 28 consecutive patients in combination with a follow-up questionnaire (n = 26, 93% response). An initial treatment effect of 89% was observed, 60% sustained at 12-month follow-up. Major side effects were hypesthesia (56%), dry eye (20%), and masseter muscle weakness (12%). A lower sensory stimulation threshold during treatment was associated with better patient satisfaction (P = 0.016), improved pain relief (P = 0.039), and trended toward more hypesthesia (P = 0.077). This low-volume study reported treatment effects in an older population that were similar to previous studies. Only a higher incidence of hypesthesia was detected by long-term follow-up. This study supported the high efficiency of RF treatment, but there was a high level of side effects. Most notable, low sensory stimulation was associated with increased hypesthesia, whereas higher stimulation levels yielded less effectiveness. Further investigation of an optimal sensory stimulation range for percutaneous RF treatment of the trigeminal ganglion was found to be warranted. © 2013 World Institute of Pain.

  5. Neuronavigator-guided percutaneous radiofrequency thermocoagulation in the treatment of trigeminal neuralgia.

    Science.gov (United States)

    Zhang, W C; Zhong, W X; Li, S T; Zheng, X S; Yang, M; Shi, J

    2012-03-01

    Although radiofrequency thermocoagulation is considered as a primary treatment for most patients with trigeminal neuralgia, neuronavigator-guided percutaneous radiofrequency thermocoagulation has been rarely reported. The object of this study was to assess the clinical value of neuronavigator-guided percutaneous radiofrequency thermocoagulation in the treatment of trigeminal neuralgia. The radiofrequency thermocoagulation was performed in 100 cases of trigeminal neuralgia. The patients were positioned supine or sitting, under Hartel's technique (reported by Sweet and Wepsic J Neurosurg 40:143-156, 1974), by anterior lateral facial approaches. The Gasserian ganglions were acupunctured, assisted by intraoperative CT scanning (3-digital reconstruction) and electrophysiology in order to accurately locate target. The needles located in oval foramen at the first puncture, the direction and position could be defined according to the electrophysiology examination. The pain alleviated immediately after operation. There occurred no serious complication and other nerve injury in all patients despite face numbness only. 3D-CT and electrophysiology Gasser's ganglion locations can raise the success rate of puncture, enhance the safety and reduce the incidence of complication, showing high academic value and its promising future.

  6. Hemorrhagic intracranial inflammatory pseudotumor originating from the trigeminal nerve: a case report.

    Science.gov (United States)

    Jung, Tae-Young; Jung, Shin; Lee, Min-Cheol; Moon, Kyung-Sub; Kim, In-Young; Kang, Sam-Suk; Kim, Soo-Han

    2006-01-01

    We report here on a case of intracranial inflammatory pseudotumor arising from the trigeminal nerve. A 52-year-old man presented with sudden onset severe headache. He had had facial numbness several months earlier and no signs indicating infection. On the computerized tomography scan, intracranial hemorrhage was detected at the cerebellopontine angle. Magnetic resonance imaging demonstrated a 2.7-cm-sized, homogenously enhancing mass. A provisional diagnosis of trigeminal schwannoma was made, and suboccipital craniotomy was then performed. The mass was encapsulated and had multiple capsular veins. There was a evidence of intratumoral bleeding. It originated from the trigeminal root and was adhered to the 4th cranial nerve. Pathologic examination showed fibrovascular tissue with dense infiltrates of plasma cells and lymphocytes, some histiocytes, and occasional neutrophils and eosinophils. It showed immunopositivity for leukocyte common antigen (LCA) and immunonegativity for S-100 and lysozyme. It was also immunopositive for EBV antigen. Intracranial inflammatory pseudotumors mostly arise from dural/meningeal structures in the intracranial location. This case is the first to describe an intracranial inflammatory pseudotumor originating from a cranial nerve. The pathologic examination supported the postinfection hypothesis out of several possible pathologic mechanisms.

  7. An Open Study of Botulinum-A Toxin Treatment of Idiopathic Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Karim Nikkhah

    2015-07-01

    Full Text Available Introduction: Trigeminal Neuralgia (TN is a unilateral, recurrent, sharp facial pain disorder that is limited to the distribution of divisions of the trigeminal nerve. The aim of this study was to evaluate the efficacy of Botulinum neurotoxin type A (BTX-A for alleviating the frequency and severity of TN pain. Materials and Methods: This trial was performed as a before and after study. We treated 31 patients (15 male and 16 female with mean age of 52 year old that their diagnosis was made at least 4.5 years before. We injected BTX-A in various parts of face and particularly in the origin of mandibular and maxillary branches of trigeminal nerve. Injection volume was determined by the necessity and pain intensity measured with visual analog scale up to 100U. Patients were evaluated before and after the injection and were followed after week, and each month, for a three months period. Other related variables were recorded such as: toxin complications, pain status variations by brushing, chewing, cold weather and patient’s satisfaction with their therapy. Results: showed that after injection, pain intensity and frequency decreased after tooth brushing, chewing and cold weather (P

  8. [Herpes zoster of the trigeminal nerve: a case report and review of the literature].

    Science.gov (United States)

    Carbone, V; Leonardi, A; Pavese, M; Raviola, E; Giordano, M

    2004-01-01

    Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.

  9. Influence of intranasal and carotid cooling on cerebral temperature balance and oxygenation

    DEFF Research Database (Denmark)

    Nybo, Lars; Wanscher, Michael; Secher, Niels H.

    2014-01-01

    temperatures were measured to assess the cerebral heat balance and corresponding paired blood samples were obtained to evaluate cerebral metabolism and oxygenation at rest, following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min with carotid cooling. Intranasal cooling induced a parallel......The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood...... drop in jugular venous and arterial blood temperatures by 0.30 ± 0.08°C (mean ± SD), whereas nasal ventilation and carotid cooling failed to lower the jugular venous blood temperature. The magnitude of the arterio-venous temperature difference across the brain remained unchanged at -0.33 ± 0.05°C...

  10. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

  11. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  12. IS ATOMIZED INTRANASAL MIDAZOLAM A NOVEL SEDATIVE PREMEDICATION IN PAEDIATRIC PATIENTS?

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    Savitri D. Kabade

    2017-06-01

    Full Text Available BACKGROUND The successful conduct of anaesthesia in children depends on adequate premedication, which not only comforts the anxious child but also comforts the parents or guardians. Atomized Intranasal Midazolam is quickly absorbed through the nasal mucosa, resulting in a rapid and reliable onset of action. Clonidine has several applications in paediatric anaesthesia as a premedication and as an adjuvant in general as well as regional anaesthesia. Thus, in search of a novel premedication technique, we conducted a study to compare the effectiveness of atomized intranasal midazolam with intranasal clonidine for preoperative sedation in paediatric patients undergoing elective surgery. MATERIALS AND METHODS After obtaining Institutional Ethical Committee clearance and parent’s consent, a prospective, randomised, double-blinded clinical study was conducted in 78 children of ASA I and II, belonging to 2 - 10 years age, posted for various elective surgery. Group M (n= 39 received atomized intranasal midazolam (0.3 mg/kg and Group C (n= 39 received clonidine (4 mcg/kg instilled into both the nostrils. Sedation score (Ramsay, separation score, mask acceptance, recovery and vital parameters were recorded. Statistical analysis of data was done using IBM-SPSS version 21.0. RESULTS Mean sedation scores (± SD were higher in Group M than in Group C (at 5th minute 1.58 ± 0.55 in Group M and 1.15 ± 0.36 in Group C with P= 0.002, at 10th minute 2.34 ± 0.97 in Group M and 1.75 ± 0.71 in Group C with P= 0.008. Separation scores and mask acceptance were better with Group M than Group C. Haemodynamic parameters were similar in both the groups and no major adverse effects were noted. CONCLUSION Atomized intranasal midazolam produces superior sedation levels, child-parent separation and mask acceptance compared to intranasal clonidine in children.

  13. Effect of intranasally administered insulin on cerebral blood flow and perfusion

    DEFF Research Database (Denmark)

    Akintola, Abimbola A.; van Opstal, Anna M.; Westendorp, Rudi G.

    2017-01-01

    Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin...... labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68...

  14. Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

    Science.gov (United States)

    Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

    2017-12-01

    Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

  15. Spontaneous behavioral responses in the orofacial region: A model of trigeminal pain in mouse

    Science.gov (United States)

    Romero-Reyes, Marcela; Akerman, Simon; Nguyen, Elaine; Vijjeswarapu, Alice; Hom, Betty; Dong, Hong-Wei; Charles, Andrew C.

    2012-01-01

    OBJECTIVES To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. BACKGROUND Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. METHODS C57BL/6 mice received either an injection of 0.9% Saline solution or complete Freund’s adjuvant (CFA) into the right masseter muscle. Animals were video recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hrs, mice were euthanized, perfused and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate, to determine the nociceptive-specific nature of their behaviors. RESULTS We characterized and quantified 3 distinct patterns of acute grooming behaviors: fore-paw rubbing, lower lip skin/cheek rubbing against enclosure floor and hind paw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. CFA

  16. Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

    Science.gov (United States)

    Dos Reis, Renata C; Kopruszinski, Caroline M; Nones, Carina F M; Chichorro, Juliana G

    2016-09-01

    There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain.

  17. Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

    DEFF Research Database (Denmark)

    Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven

    2014-01-01

    : In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

  18. Cortisol, but not intranasal insulin, affects the central processing of visual food cues

    NARCIS (Netherlands)

    Ferreira de Sá, D.S.; Schulz, A.; Streit, F.E.; Turner, J.D.; Oitzl, M.S.; Blumenthal, T.D.; Schächinger, H.

    2014-01-01

    Stress glucocorticoids and insulin are important endocrine regulators of energy homeostasis, but little is known about their central interaction on the reward-related processing of food cues. According to a balanced group design, healthy food deprived men received either 40IU intranasal insulin

  19. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    Science.gov (United States)

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  20. Efektivitas Terapi Kortikosteroid Intranasal pada Hipertrofi Adenoid Usia Dewasa berdasarkan Pemeriksaan Narrow Band Imaging

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    Sinta Sari Ratunanda

    2016-12-01

    Full Text Available Adenoid hypertrophy is a process in which adenoid size becomes enlarged and causes clinical symptoms, especially nasal obstruction. Adenoid hypertrophy can be due to physiological, inflammatory, or malignancy processes. Adenoid inflammatory process can be assessed using a flexible fiberoptic nasoendoscopy with narrow band imaging (NBI. Intranasal corticosteroid is one of the choices to treat adenoid hypertrophy in children; however, more experiments are needed to use it in adults. This study was performed in the period of November 2012 to January 2013 at the outpatient clinic of the Otorhinolaryngology-Head and Neck Surgery Department of Dr. Hasan Sadikin General Hospital Bandung, using pre- and post-test open-labeled quasiexperimental design. Sample was selected through consecutive sampling, involving 11 subjects. Diagnosis was based on research subject’s anamnesis, ear nose and throat (ENT physical examination, NBI-equipped fiberoptic nasoendocopy examination, and adenoid mucosal biopsy. Subjects were given intranasal corticosteroid therapy for four weeks. NBI-equipped fiberoptic nasoendocopy examination and biopsy examination were performed after therapy. Data were analyzed using Wilcoxon test, showing significant improvement of the adenoid inflammation after intranasal corticosteroids therapy (p<0.05. McNemar test results showed a significant reduction in adenoid size (p<0.05. Spearman rank test showed a significant correlation between histopathologic findings and NBI examination result (p<0.05. In conclusion, intranasal corticosteroids are effective for adult adenoid hypertrophy treatment based on NBI examination. [MKB. 2016;48(4:228–33

  1. Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

    Science.gov (United States)

    Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

    2008-07-04

    In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, pnanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, pintramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

  2. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...

  3. CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

    Directory of Open Access Journals (Sweden)

    Olga Dal Monte

    Full Text Available Oxytocin (OT in the central nervous system (CNS influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline to 15 primates (Macaca mulatta, using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

  4. Efficacy of Intranasal Scopolamine Gel for Motion Sickness Treatment in Aviation Candidates

    Science.gov (United States)

    2009-04-13

    Baseline 15 25 80 115 145 190 M ea n B lo o d P re ss u re (m m H g ) 0 20 40 60 80 100 120 140 Systolic BP P Systolic BPIN Diastolic BPP Diastolic...scopolamine when compared to placebo, p < .05. BPP = Blood Pressure, Placebo, BPIN = Blood Pressure, Intranasal Scopolamine 31 Time (min) Baseline 15 25 80

  5. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs

    NARCIS (Netherlands)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, Liesbeth

    2016-01-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for

  6. Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis

    NARCIS (Netherlands)

    Wellenberg, G.J.; Bruschke, C.J.M.; Wisselink, H.J.; Barkema, H.W.; Oirschot, van J.T.

    2002-01-01

    In this study, we examined whether an experimental bovine herpesvirus 4 (BHV4) infection can induce bovine mastitis, or can enhance bovine mastitis induced by Streptococcus uberis (S. uberis). Four lactating cows were inoculated intramammarily and intranasally with BHV4, and four lactating control

  7. Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine.

    Science.gov (United States)

    Weerts, Aurélie P; Pattyn, Nathalie; Putcha, Lakshmi; Hoag, Stephen W; Van Ombergen, Angelique; Hallgren, Emma; Van de Heyning, Paul H; Wuyts, Floris L

    2015-12-01

    Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. This double-blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. © The Author(s) 2015.

  8. Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

    Science.gov (United States)

    Skoner, D P; Doyle, W J; Boehm, S; Fireman, P

    1991-12-01

    Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

  9. A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs.

    Science.gov (United States)

    Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

    2009-08-01

    To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.

  10. Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery.

    Science.gov (United States)

    Soliman, Mahmoud E; Elmowafy, Enas; Casettari, Luca; Alexander, Cameron

    2018-05-30

    The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    Science.gov (United States)

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Warfvinge, K; Kruse, L S

    2016-01-01

    modify the neurogenic inflammatory response in the trigeminal ganglion. METHODS: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were...... investigated using immunohistochemistry and Western blot. FINDINGS: Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. CONCLUSIONS......: This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates....

  13. A Comparative Study between Oxcarbazepine and Gabapentin Regarding Therapeutic Efficiency and Tolerability in the Treatment of Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Fakir Mohan Debta

    2010-01-01

    Recently two newer anticonvulsant oxcarbazepine (OXC a ketoderivative of carbamazepine and gabapentin (GBP has been trailed in trigeminal neuralgia in different open clinical trial as monotherapy with encouraging results. These drugs have convenient dosage and surprisingly fewer side effects. These facts that trigeminal neuralgia responds to newer anticonvulsant (oxcarbazepine, gabapentin in a better perspective, enabled me to conduct the present clinical trial on 54 patients (both in newly diagnosed TN patient and refractive patient of trigeminal neuralgia who were made two randomized group for separate monotherapy study for a period of six months. The therapeutic effect of OXC and gabapentin (GBP in relation to reduction in number of attacks of pain and severity of pain were evaluated. All the scoring data showed OXC is more therapeutic efficacious cost-effective and well-tolerated profile than gabapentin and an emerging as a drug for treatment of TN in both new and refractive patients.

  14. [Pure trigeminal motor neuropathy presenting with temporo-mandibular joint dysfunction in a patient with HIV and HCV infections].

    Science.gov (United States)

    Anheim, M; Echaniz-Laguna, A; Rey, D; Tranchant, C

    2006-01-01

    Pure trigeminal motor neuropathy (PTMN) is a rarely described condition. We report the case of a 41-year-old woman infected with the human immunodeficiency virus (HIV1) and hepatitis C virus who presented with weakness of left temporalis and masseter muscles and painful left temporomandibular joint dysfunction (TMD) a few months after cerebral toxoplasmosis revealing acquired immunodeficiency syndrome (AIDS). Magnetic resonance imaging revealed severe wasting and fat replacement of the left temporalis, pterygoid and masseter muscles and showed neither abnormalities in the left motor nucleus of the trigeminal nerve nor compression of the left trigeminal nerve. Electromyographic examination gave evidence of denervation in the left temporalis, masseter and pterygoid muscles and blink reflex studies were normal, confirming the diagnosis of PTMN which was probably secondary to HIV and HCV co-infection.

  15. The Role of Nav1.9 Channel in the Development of Neuropathic Orofacial Pain Associated with Trigeminal Neuralgia.

    Science.gov (United States)

    Lulz, Ana Paula; Kopach, Olga; Santana-Varela, Sonia; Wood, John N

    2015-01-01

    Trigeminal neuralgia is accompanied by severe mechanical, thermal and chemical hypersensitivity of the orofacial area innervated by neurons of trigeminal ganglion (TG). We examined the role of the voltage-gated sodium channel subtype Nav1.9 in the development of trigeminal neuralgia. We found that Nav1.9 is required for the development of both thermal and mechanical hypersensitivity induced by constriction of the infraorbital nerve (CION). The CION model does not induce change on Nav1.9 mRNA expression in the ipsilateral TG neurons when evaluated 9 days after surgery. These results demonstrate that Nav1.9 channels play a critical role in the development of orofacial neuropathic pain. New routes for the treatment of orofacial neuropathic pain focussing on regulation of the voltage-gated Nav1.9 sodium channel activity should be investigated. © 2015 Luiz et al.

  16. Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

    Science.gov (United States)

    Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

    2017-11-17

    Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

  17. Effects of Intranasal Oxytocin on the Interpretation and Expression of Emotions in Anorexia Nervosa.

    Science.gov (United States)

    Leppanen, J; Cardi, V; Ng, K W; Paloyelis, Y; Stein, D; Tchanturia, K; Treasure, J

    2017-03-01

    Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli. © 2017 The Authors. Journal of Neuroendocrinology

  18. Conditioned social preference, but not place preference, produced by intranasal oxytocin in female mice.

    Science.gov (United States)

    Kosaki, Yutaka; Watanabe, Shigeru

    2016-04-01

    Oxytocin (OT) has been implicated in a variety of mammalian reproductive and social behaviors, and the use of intranasal OT for clinical purposes is on the rise. However, basic actions of OT, including the rewarding or reinforcing properties of the drug, are currently not fully understood. In this study, the authors investigated whether intranasally administered OT has different reinforcing properties for social and nonsocial stimuli and whether such effects are variable between male and female subjects. Conditioned social preference (CSP) and conditioned place preference (CPP) paradigms were used to examine social and nonsocial reinforcing properties of OT. In CSP, the presence of a same-sex unfamiliar conspecific was repeatedly paired with intranasal OT, while a different conspecific was associated with saline. The reinforcing effect of OT was assessed in a postconditioning choice test under a drug-free condition. In CPP, the 2 conspecifics were replaced with nonsocial black and white compartments. The authors found that intranasal OT (12 μg) in females supported the formation of CSP (Experiment 1) but not CPP (Experiment 3). Neither CSP (Experiment 2) nor CPP (Experiment 4) was formed in males. Extended conditioning with higher dose OT (36 μg), however, abolished the initial CSP in females and produced an aversion to the OT-paired stimulus mouse. Experiment 5 indicated that it was the repeated administrations rather than the higher dose that produced the abolition of the original preference. Overall, the current results demonstrate for the first time a sex- and stimulus-dependent reinforcing property of intranasal OT in mice. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. Long-term exposure to intranasal oxytocin in a mouse autism model.

    Science.gov (United States)

    Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P

    2014-11-11

    Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

  20. The Effects of Oral d-Amphetamine on Impulsivity in Smoked and Intranasal Cocaine Users

    Science.gov (United States)

    Reed, Stephanie Collins; Evans, Suzette M.

    2016-01-01

    BACKGROUND Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. METHODS The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. RESULTS Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). CONCLUSIONS Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. PMID:27114203

  1. Oral Squamous Cell Carcinoma Found Inline with the Fields of Repeat Stereotactic Radiosurgery for Recurrent Trigeminal Neuralgia.

    Science.gov (United States)

    Berti, Aldo; Granville, Michelle; Jacobson, Robert E

    2018-01-12

    A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65.5 Gy to the same retrogasserian area of the trigeminal nerve, making the total cumulative dose 125.5 Gy. In late 2016, four years after the 2 nd SRS, he was found to have invasive keratinizing squamous cell carcinoma in the left posterior mandibular oral mucosa. Keratinizing squamous cell carcinoma is seen primarily in smokers or associated with the human papillomavirus, neither of which was found in this patient. A review of his two SRS plans shows that the left lower posterior mandibular area was clearly within the radiation fields for both SRS treatments. It is postulated that his cancer developed secondary to the long-term radiation effect with a very localized area being exposed twice to a focused, cumulative, high-dose radiation. There are individual reports in the literature of oral mucositis immediately after radiation for trigeminal neuralgia and the delayed development of malignant tumors, including glioblastoma found after SRS for acoustic neuromas, but there are no reports of delayed malignant tumors developing within the general radiation field. Using repeat SRS is an accepted treatment for recurrent trigeminal neuralgia, but physicians and patients should be aware of the potential effects of higher cumulative radiation effects within the treatment field when patients undergo repeat procedures.

  2. Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

    Science.gov (United States)

    Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L

    2017-08-01

    Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes. NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal

  3. Effect of neonatal capsaicin treatment on neural activity in the medullary dorsal horn of neonatal rats evoked by electrical stimulation to the trigeminal afferents: an optical, electrophysiological, and quantitative study.

    Science.gov (United States)

    Takuma, S

    2001-07-06

    To elucidate which glutamate receptors, NMDA or non-NMDA, have the main role in synaptic transmission via unmyelinated afferents in the trigeminal subnucleus caudalis (the medullary dorsal horn), and to examine the early functional effects of neonatal capsaicin treatment to the subnucleus caudalis, optical recording, field potential recording, and quantitative study using electron micrographs were employed. A medulla oblongata isolated from a rat 5--7 days old was sectioned horizontally 400-microm thick or parasagittally and stained with a voltage-sensitive dye, RH482 or RH795. Single-pulse stimulation with high intensity to the trigeminal afferents evoked optical responses mainly in the subnucleus caudalis. The optical signals were composed of two phases, a fast component followed by a long-lasting component. The spatiotemporal properties of the optical signals were well correlated to those of the field potentials recorded simultaneously. The fast component was eliminated by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM), while the long-lasting component was not. The latter increased in amplitude under a condition of low Mg(2+) but was significantly reduced by DL-2-amino-5-phosphonovaleric acid (AP5; 30 microM). Neonatal capsaicin treatment also reduced the long-lasting component markedly. In addition, the decreases in the ratio of unmyelinated axons to myelinated axons and in the ratio of unmyelinated axons to Schwann cell subunits of trigeminal nerve roots both showed significant differences (P<0.05, Student's t-test) between the control group and the neonatal capsaicin treatment group. This line of evidence indirectly suggests that synaptic transmission via unmyelinated afferents in the subnucleus caudalis is mediated substantially by NMDA glutamate receptors and documented that neonatal capsaicin treatment induced a functional alteration of the neural transmission in the subnucleus caudalis as well as a morphological alteration of primary afferents

  4. Activation properties of trigeminal motoneurons in participants with and without bruxism

    Science.gov (United States)

    D'Amico, Jessica M.; Yavuz, Ş. Utku; Saraçoğlu, Ahmet; Atiş, Elif Sibel; Türker, Kemal S.

    2013-01-01

    In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities such as eating, nonnutritive chewing, clenching, and yawning

  5. Microvascular Decompression for Treatment of Trigeminal Neuralgia in Patient with Facial Nerve Schwannoma.

    Science.gov (United States)

    Marinelli, John P; Van Gompel, Jamie J; Link, Michael J; Carlson, Matthew L

    2018-05-01

    Secondary trigeminal neuralgia (TN) is uncommon. When a space-occupying lesion with mass effect is identified, the associated TN is often exclusively attributed to the tumor. This report illustrates the importance of considering coexistent actionable pathology when surgically treating secondary TN. A 51-year-old woman presented with abrupt-onset TN of the V2 and V3 nerve divisions with hypesthesia. She denied changes in hearing, balance, or facial nerve dysfunction. Magnetic resonance imaging revealed a 1.6-cm contrast-enhancing cerebellopontine angle tumor that effaced the trigeminal nerve, consistent with a vestibular schwannoma. In addition, a branch of the superior cerebellar artery abutted the cisternal segment of the trigeminal nerve on T2-weighted thin-slice magnetic resonance imaging. Intraoperative electrical stimulation of the tumor elicited a response from the facial nerve at low threshold over the entire accessible tumor surface, indicating that the tumor was a facial nerve schwannoma. Considering the patient's lack of facial nerve deficit and that the tumor exhibited no safe entry point for intracapsular debulking, tumor resection was not performed. Working between the tumor and tentorium, a branch of the superior cerebellar artery was identified and decompressed with a Teflon pad. At last follow-up, the patient exhibited resolution of her TN. Her hearing and facial nerve function remained intact. Despite obstruction from a medium-sized tumor, it is still possible to achieve microvascular decompression of the fifth cranial nerve. This emphasizes the importance of considering other actionable pathology during surgical management of presumed tumor-induced TN. Further, TN is relatively uncommon with medium-sized vestibular schwannomas and coexistent causes should be considered. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats

    Science.gov (United States)

    Kim, Hye-Jin; Lee, Geun-Woo; Kim, Min-Ji; Yang, Kui-Ye; Kim, Seong-Taek; Bae, Yong-Cheol

    2015-01-01

    We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions. PMID:26170739

  7. Neurons within the trigeminal mesencephalic nucleus encode for the kinematic parameters of the whisker pad macrovibrissae.

    Science.gov (United States)

    Mameli, Ombretta; Caria, Marcello A; Biagi, Francesca; Zedda, Marco; Farina, Vittorio

    2017-05-01

    It has been recently shown in rats that spontaneous movements of whisker pad macrovibrissae elicited evoked responses in the trigeminal mesencephalic nucleus (Me5). In the present study, electrophysiological and neuroanatomical experiments were performed in anesthetized rats to evaluate whether, besides the whisker displacement per se, the Me5 neurons are also involved in encoding the kinematic properties of macrovibrissae movements, and also whether, as reported for the trigeminal ganglion, even within the Me5 nucleus exists a neuroanatomical representation of the whisker pad macrovibrissae. Extracellular electrical activity of single Me5 neurons was recorded before, during, and after mechanical deflection of the ipsilateral whisker pad macrovibrissae in different directions, and with different velocities and amplitudes. In several groups of animals, single or multiple injections of the tracer Dil were performed into the whisker pad of one side, in close proximity to the vibrissae follicles, in order to label the peripheral terminals of the Me5 neurons innervating the macrovibrissae (whisking-neurons), and therefore, the respective perikaria within the nucleus. Results showed that: (1) the whisker pad macrovibrissae were represented in the medial-caudal part of the Me5 nucleus by a single cluster of cells whose number seemed to match that of the macrovibrissae; (2) macrovibrissae mechanical deflection elicited significant responses in the Me5 whisking-neurons, which were related to the direction, amplitude, and frequency of the applied deflection. The specific functional role of Me5 neurons involved in encoding proprioceptive information arising from the macrovibrissae movements is discussed within the framework of the whole trigeminal nuclei activities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. Intractable trigeminal neuralgia: A single institution experience in 26 patients treated with stereotactic gamma knife radiosurgery

    International Nuclear Information System (INIS)

    Mark, Rufus J.; Duma, Christopher M.; Jacques, Dean B.; Kopyov, Oleg V.; Copcutt, Brian

    1996-01-01

    Purpose: In patients with trigeminal neuralgia, severe pain can persist, or recur despite aggressive medical management and open surgery. Recently, Gamma Knife radiosurgery has been used with promising results. We report on our series of 26 patients with intractable trigeminal neuralgia treated with stereotactic Gamma Knife radiosurgery. Materials and Methods: Between 1991 and 1995, 26 patients with intractable trigeminal neuralgia were treated at our institution using stereotactic Gamma Knife radiosurgery. Medical management had failed in all cases. In addition, 13 patients underwent a total of 20 open surgeries, with transient, or no pain relief. There were 19 females, and 7 males. Patient ages ranged from 37 to 87 years, with a median of 74 years. All patients were treated with a 201 source Cobalt-60 Gamma Knife unit. All patients underwent placement of the Leksell frame, followed by MRI scanning and computer treatment planning. The target in all patients was the fifth cranial nerve root entry zone into the brainstem. Twenty-five patients received between 64.3 to 70 Gy prescribed to Dmax in one shot. One patient received 120 Gy to Dmax in one shot. The 4 mm collimator was used in 22 cases, and the 8 mm in 4 cases. Follow-up ranged from 5 to 55 months, with a median of 19 months. Complete resolution (CR) of pain was scored when the patient reported being pain free off all medication. Partial resolution (PR) was scored when the patient reported > 50% pain reduction after Gamma Knife treatment. Results: At last follow-up, 84.6% ((22(26))) reported CR or PR of pain after Gamma Knife treatment. Forty-two percent ((11(26))) of patients reported CR, and 42%((11(26))) reported PR of pain. There was a dose response. In patients receiving < 70 Gy, 25% ((3(12))) reported CR, while 57% ((8(14))) of those receiving ≥ 70 Gy reported CR. Complications occurred in two (8%) patients. One patient developed transient numbness of the face after 70 Gy, and a second patient

  9. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Arvind Chaturvedi

    2011-01-01

    Full Text Available Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

  10. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia.

    Science.gov (United States)

    Chaturvedi, Arvind; Dash, Hh

    2011-07-01

    Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

  11. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    Directory of Open Access Journals (Sweden)

    Almeida A

    2011-08-01

    Full Text Available Laurinda Lemos1,2, Carlos Alegria3, Joana Oliveira3, Ana Machado2, Pedro Oliveira4, Armando Almeida11Life and Health Sciences Research Institute (ICVS, School of Health Sciences, Campus de Gualtar, University of Minho, Braga, Portugal; 2Hospital Center of Alto Ave, Unit of Fafe, Fafe, Portugal; 3Department of Neurosurgery, Hospital São Marcos; 4Products and Systems Engineering, Campus de Azurém, University of Minho, Guimarães, PortugalAbstract: In idiopathic trigeminal neuralgia (TN the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1 a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol], (2 the association of gabapentin (GBP and analgesic block of trigger-points with ropivacaine (ROP (GBP+ROP protocol, and (3 a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol. Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols from cases of idiopathic TN, or selected for MVD surgery (n = 22 due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug

  12. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    International Nuclear Information System (INIS)

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H.; Murray, R.S.

    1988-01-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia

  13. Presurgical visualization of the neurovascular relationship in trigeminal neuralgia with 3D modeling using free Slicer software.

    Science.gov (United States)

    Han, Kai-Wei; Zhang, Dan-Feng; Chen, Ji-Gang; Hou, Li-Jun

    2016-11-01

    To explore whether segmentation and 3D modeling are more accurate in the preoperative detection of the neurovascular relationship (NVR) in patients with trigeminal neuralgia (TN) compared to MRI fast imaging employing steady-state acquisition (FIESTA). Segmentation and 3D modeling using 3D Slicer were conducted for 40 patients undergoing MRI FIESTA and microsurgical vascular decompression (MVD). The NVR, as well as the offending vessel determined by MRI FIESTA and 3D Slicer, was reviewed and compared with intraoperative manifestations using SPSS. The k agreement between the MRI FIESTA and operation in determining the NVR was 0.232 and that between the 3D modeling and operation was 0.6333. There was no significant difference between these two procedures (χ 2  = 8.09, P = 0.088). The k agreement between the MRI FIESTA and operation in determining the offending vessel was 0.373, and that between the 3D modeling and operation was 0.922. There were significant differences between two of them (χ 2  = 82.01, P = 0.000). The sensitivity and specificity for MRI FIESTA in determining the NVR were 87.2 % and 100 %, respectively, and for 3D modeling were both 100 %. The segmentation and 3D modeling were more accurate than MRI FIESTA in preoperative verification of the NVR and offending vessel. This was consistent with surgical manifestations and was more helpful for the preoperative decision and surgical plan.

  14. Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.

    Directory of Open Access Journals (Sweden)

    Nicole Schöbel

    Full Text Available Intracellular Cl(- concentrations ([Cl(-](i of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG and olfactory sensory neurons (OSNs, Cl(- is accumulated by the Na(+-K(+-2Cl(- cotransporter 1 (NKCC1, resulting in a [Cl(-](i above electrochemical equilibrium and a depolarizing Cl(- efflux upon Cl(- channel opening. Here, we investigate the [Cl(-](i and function of Cl(- in primary sensory neurons of trigeminal ganglia (TG of wild type (WT and NKCC1(-/- mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-](i of WT TG neurons indicated active NKCC1-dependent Cl(- accumulation. Gamma-aminobutyric acid (GABA(A receptor activation induced a reduction of [Cl(-](i as well as Ca(2+ transients in a corresponding fraction of TG neurons. Ca(2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+ channels (VGCCs. Ca(2+ responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1 were diminished in NKCC1(-/- TG neurons, but elevated under conditions of a lowered [Cl(-](o suggesting a Cl(--dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS, we found expression of different Ca(2+-activated Cl(- channels (CaCCs in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+ imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/- mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+-activated Cl(--dependent signal amplification mechanism in TG neurons that requires intracellular Cl(- accumulation by NKCC1 and the activation of CaCCs.

  15. Safety and Immunogenicity Testing of an Intranasal Group B Meningococcal Native Outer Membrane Vesicle Vaccine in Healthy Volunteers

    National Research Council Canada - National Science Library

    Drabick, Joseph

    1998-01-01

    An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain and tested in 32 healthy adult volunteers...

  16. Causality Assessment of Olfactory and Gustatory Dysfunction Associated with Intranasal Fluticasone Propionate: Application of the Bradford Hill Criteria

    OpenAIRE

    Muganurmath, Chandrashekhar S.; Curry, Amy L.; Schindzielorz, Andrew H.

    2018-01-01

    Causality assessment is crucial to post-marketing pharmacovigilance and helps optimize safe and appropriate use of medicines by patients in the real world. Self-reported olfactory and gustatory dysfunction are common in the general population as well as in patients with allergic rhinitis and nasal polyposis. Intranasal corticosteroids, including intranasal fluticasone propionate (INFP), are amongst the most effective drugs indicated in the treatment of allergic rhinitis and nasal polyposis. W...

  17. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial

    OpenAIRE

    Schmidt, Heinrich; Giese, Renate; Enders, Angelika; Kern, W.; Hallschmid, M.

    2009-01-01

    Background: The 22q13 deletion syndrome (Phelan– McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. Aims: To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 delet...

  18. Association between neurovascular contact on MRI and response to gamma knife radiosurgery in trigeminal neuralgia

    International Nuclear Information System (INIS)

    Erbay, Sami H.; Bhadelia, Rafeeque A.; Gupta, Punita; O'Callaghan, Mark; Yun, Eric; Oljeski, Steven; Riesenburger, Ron

    2006-01-01

    Treatment with gamma knife radiosurgery (GKRS) provides adequate short-term pain control in about 70% of the patients with intractable trigeminal neuralgia (TN). The purpose of our study was to evaluate whether the presence of neurovascular contact (NVC) at the root entry zone of the trigeminal nerve on pre-gamma knife MR imaging predicts an increased likelihood of an adequate response to GKRS.We studied 40 consecutive patients who underwent GKRS for treatment of intractable TN. Two neuroradiologists blinded to the side of symptoms analyzed pre-treatment constructive interference in steady state (CISS) images to determine the presence of NVC by consensus. An adequate response was defined as freedom from pain with or without reduced need for medical therapy. Adequate short-term response to GKRS was seen in 29 (72.5%) of 40 patients. NVC was seen in 30 of the 40 patients. Twenty-five (83.3%) of 30 patients with NVC had adequate short-term response to GKRS. Only four (40%) of the 10 patients without NVC had adequate response to GKRS (X 2 =7.06; P<0.01). Patients with NVC were seven times more likely to have an adequate response to GKRS than those without NVC (odds ratio =7.5).The presence of NVC on pre-treatment MR imaging predicts an increased likelihood of an adequate response to GKRS. (orig.)

  19. SU-E-T-420: Failure Effects Mode Analysis for Trigeminal Neuralgia Frameless Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Howe, J [Associates In Medical Physics, Louisville, KY (United States)

    2015-06-15

    Purpose: Functional radiosurgery has been used successfully in the treatment of trigeminal neuralgia but presents significant challenges to ensuring the high prescription dose is delivered accurately. A review of existing practice should help direct the focus of quality improvement for this treatment regime. Method: Failure modes and effects analysis was used to identify the processes in preparing radiosurgery treatment for TN. The map was developed by a multidisciplinary team including: neurosurgeon, radiation oncology, physicist and therapist. Potential failure modes were identified for each step in the process map as well as potential causes and end effect. A risk priority number was assigned to each cause. Results: The process map identified 66 individual steps (see attached supporting document). Corrective actions were developed for areas of high risk priority number. Wrong site treatment is at higher risk for trigeminal neuralgia treatment due to the lack of site specific pathologic imaging on MR and CT – additional site specific checks were implemented to minimize the risk of wrong site treatment. Failed collision checks resulted from an insufficient collision model in the treatment planning system and a plan template was developed to address this problem. Conclusion: Failure modes and effects analysis is an effective tool for developing quality improvement in high risk radiotherapy procedures such as functional radiosurgery.

  20. Diagnostic and therapeutic errors in trigeminal autonomic cephalalgias and hemicrania continua: a systematic review

    Science.gov (United States)

    2013-01-01

    Trigeminal autonomic cephalalgias (TACs) and hemicrania continua (HC) are relatively rare but clinically rather well-defined primary headaches. Despite the existence of clear-cut diagnostic criteria (The International Classification of Headache Disorders, 2nd edition - ICHD-II) and several therapeutic guidelines, errors in workup and treatment of these conditions are frequent in clinical practice. We set out to review all available published data on mismanagement of TACs and HC patients in order to understand and avoid its causes. The search strategy identified 22 published studies. The most frequent errors described in the management of patients with TACs and HC are: referral to wrong type of specialist, diagnostic delay, misdiagnosis, and the use of treatments without overt indication. Migraine with and without aura, trigeminal neuralgia, sinus infection, dental pain and temporomandibular dysfunction are the disorders most frequently overdiagnosed. Even when the clinical picture is clear-cut, TACs and HC are frequently not recognized and/or mistaken for other disorders, not only by general physicians, dentists and ENT surgeons, but also by neurologists and headache specialists. This seems to be due to limited knowledge of the specific characteristics and variants of these disorders, and it results in the unnecessary prescription of ineffective and sometimes invasive treatments which may have negative consequences for patients. Greater knowledge of and education about these disorders, among both primary care physicians and headache specialists, might contribute to improving the quality of life of TACs and HC patients. PMID:23565739

  1. Oxcarbazepine: a new drug in the management of intractable trigeminal neuralgia.

    Science.gov (United States)

    Zakrzewska, J M; Patsalos, P N

    1989-01-01

    The efficacy and tolerability of oxcarbazepine, a keto derivative of carbamazepine, has been assessed in six patients (two males, four females; mean age 61 years, range 42-77), with trigeminal neuralgia refractory to carbamazepine therapy, over a period of 6 months. An excellent therapeutic response to oxcarbazepine was seen in all patients with pain control correlating well with serum drug concentrations of oxcarbazepine and its primary active metabolite 10-OH-carbazepine. Onset of the effect was observed within 24 hours in all cases. An overall serum therapeutic concentration range, in the six patients, of 50-110 mumol/l of 10-OH-carbazepine corresponding to a daily effective dose range of 1200-2400 mg (14.6-35.6 mg/kg body weight) oxcarbazepine, was observed. There was a significant correlation between oxcarbazepine dose and serum oxcarbazepine (r = 0.695, p less than 0.05) and 10-OH-carbazepine (r = 0.957, p less than 0.001) concentrations. Oxcarbazepine was well tolerated and no significant side effects were identified, though a mild hyponatraemia was observed during high doses (greater than 28 and greater than 35 mg/kg/day) in two patients. It is concluded that oxcarbazepine has potent antineuralgic properties in the absence of significant side effects and therefore may be useful in the management of intractable trigeminal neuralgia. Images PMID:2738589

  2. Facial hyperalgesia due to direct action of endothelin-1 in the trigeminal ganglion of mice.

    Science.gov (United States)

    Gomes, Lenyta Oliveira; Chichorro, Juliana Geremias; Araya, Erika Ivanna; de Oliveira, Jade; Rae, Giles Alexander

    2018-03-23

    This study assessed the ability of endothelin-1 (ET-1) to evoke heat hyperalgesia when injected directly into the trigeminal ganglia (TG) of mice and determined the receptors implicated in this effect. The effects of TG ET A and ET B receptor blockade on alleviation of heat hyperalgesia in a model of trigeminal neuropathic pain induced by infraorbital nerve constriction (CION) were also examined. Naive mice received an intraganglionar (i.g.) injection of ET-1 (0.3-3 pmol) or the selective ET B R agonist sarafotoxin S6c (3-30 pmol), and response latencies to ipsilateral heat stimulation were assessed before the treatment and at 1-h intervals up to 5 h after the treatment. Heat hyperalgesia induced by i.g. ET-1 or CION was assessed after i.g. injections of ET A R and ET B R antagonists (BQ-123 and BQ-788, respectively, each at 0.5 nmol). Intraganglionar ET-1 or sarafotoxin S6c injection induced heat hyperalgesia lasting 4 and 2 h, respectively. Heat hyperalgesia induced by ET-1 was attenuated by i.g. BQ-123 or BQ-788. On day 5 after CION, i.g. BQ-788 injection produced a more robust antihyperalgesic effect compared with BQ-123. ET-1 injection into the TG promotes ET A R/ET B R-mediated facial heat hyperalgesia, and both receptors are clearly implicated in CION-induced hyperalgesia in the murine TG system. © 2018 Royal Pharmaceutical Society.

  3. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.

    Directory of Open Access Journals (Sweden)

    Caroline Flegel

    Full Text Available The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq to conduct the first expression analysis of human trigeminal ganglia (TG and dorsal root ganglia (DRG. We analyzed the data with a focus on G-protein coupled receptors (GPCRs and ion channels, which are (potentially involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues.

  4. SU-E-T-420: Failure Effects Mode Analysis for Trigeminal Neuralgia Frameless Radiosurgery

    International Nuclear Information System (INIS)

    Howe, J

    2015-01-01

    Purpose: Functional radiosurgery has been used successfully in the treatment of trigeminal neuralgia but presents significant challenges to ensuring the high prescription dose is delivered accurately. A review of existing practice should help direct the focus of quality improvement for this treatment regime. Method: Failure modes and effects analysis was used to identify the processes in preparing radiosurgery treatment for TN. The map was developed by a multidisciplinary team including: neurosurgeon, radiation oncology, physicist and therapist. Potential failure modes were identified for each step in the process map as well as potential causes and end effect. A risk priority number was assigned to each cause. Results: The process map identified 66 individual steps (see attached supporting document). Corrective actions were developed for areas of high risk priority number. Wrong site treatment is at higher risk for trigeminal neuralgia treatment due to the lack of site specific pathologic imaging on MR and CT – additional site specific checks were implemented to minimize the risk of wrong site treatment. Failed collision checks resulted from an insufficient collision model in the treatment planning system and a plan template was developed to address this problem. Conclusion: Failure modes and effects analysis is an effective tool for developing quality improvement in high risk radiotherapy procedures such as functional radiosurgery

  5. The role of trigeminal function in the sensation of nasal obstruction in chronic rhinosinusitis.

    Science.gov (United States)

    Saliba, Joe; Fnais, Naif; Tomaszewski, Marcel; Carriere, Junie S; Frenkiel, Saul; Frasnelli, Johannes; Tewfik, Marc A

    2016-05-01

    Trigeminal sensation (TS) within the nasal cavity is important for the perception of nasal airflow. The objective of this study is to examine whether impaired TS contributes to the sensation of nasal obstruction in patients with chronic rhinosinusitis (CRS). Prospective case-control study conducted in a tertiary referral rhinology clinic. Cases consisted of CRS patients with subjective nasal obstruction, not previously treated with oral corticoids. Controls consisted of patients without CRS. Neither group demonstrated obvious anatomical obstructions. Both groups underwent peak nasal inspiratory flows (PNIF), olfactory testing (quick eight-item odor identification test), and trigeminal testing (lateralization task using eucalyptol and odorless solvent). A total of 28 subjects (14 CRS patients and 14 controls) were recruited. Analyses revealed no statistical differences in age (P = .93), gender (P = .47), or PNIF (P = .82) between the two groups, but they differed in Lund-Mackay scores (P sensation of nasal obstruction in CRS. 3b. Laryngoscope, 126:E174-E178, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  6. Chronic tooth pulp inflammation induces persistent expression of phosphorylated ERK (pERK) and phosphorylated p38 (pp38) in trigeminal subnucleus caudalis

    Science.gov (United States)

    Worsley, M.A.; Allen, C.E.; Billinton, A.; King, A.E.; Boissonade, F.M.

    2014-01-01

    Background Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc. Results Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types. Conclusions This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in

  7. Enhanced short-term sensitization of facial compared with limb heat pain.

    Science.gov (United States)

    Schmidt, Katharina; Schunke, Odette; Forkmann, Katarina; Bingel, Ulrike

    2015-08-01

    Habituation and sensitization are important features of individual sensitivity to repetitive noxious stimulation and have been investigated in numerous studies. However, it is unclear whether these phenomena vary depending on the site of stimulation. Here we compared short-term and long-term effects of painful heat stimulation on the forehead and limb using an established longitudinal heat pain paradigm performed over 8 consecutive days in 36 healthy volunteers. Participants were randomized into 2 groups; participants received repetitive heat pain stimulation either on the left volar forearm or on the left side of the forehead. Our data show a comparable degree of habituation over the course of 8 days in both groups. However, participants in the trigeminal stimulation group exhibited stronger within-session sensitization (indexed by a higher within-session increase in pain intensity ratings) than those who received the forearm stimulation. Furthermore, over the course of the experiment we found a correlation between habituation and anxiety, showing less habituation in participants with higher trait anxiety scores. Our findings are in line with somatotopic differences in response to painful stimulation and a higher proneness of trigeminal pain to sensitization processes, which might be explained by the biological relevance of the head and facial area for vital functions. The contribution of this sensitivity to the development and maintenance of clinical facial pain and headache disorders warrants further investigation. This study uses psychophysical methods to evaluate the differences in long-term habituation and short-term sensitization to heat pain between the trigeminal and spinal systems. We found stronger sensitization for trigeminal compared with nociceptive stimuli on the forearm. The contribution of this sensitivity to clinical pain states warrants further investigation. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  8. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

    Science.gov (United States)

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Eldar-Finkelman, Hagit; Martinez, Ana; Faghihi, Mohammad A; Jope, Richard S; Beurel, Eleonore

    2017-03-23

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1 -/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

  9. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

    Science.gov (United States)

    Daughters, Katie; Manstead, Antony S R; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H M

    2015-01-01

    The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

  10. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

    Directory of Open Access Journals (Sweden)

    Katie Daughters

    Full Text Available The use of intranasal oxytocin (OT in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

  11. Effect of administration method, animal weight and age on the intranasal delivery of drugs to the brain.

    Science.gov (United States)

    Krishnan, Jishnu K S; Arun, Peethambaran; Chembukave, Bhadra; Appu, Abhilash P; Vijayakumar, Nivetha; Moffett, John R; Puthillathu, Narayanan; Namboodiri, Aryan M A

    2017-07-15

    The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ( 3 H-2-PAM) to the brain of rats. We found that using upright vs. supine posture did not significantly affect 3 H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

    Science.gov (United States)

    Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

    2016-01-01

    Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

  13. Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

    Science.gov (United States)

    Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

    2016-02-01

    To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

    DEFF Research Database (Denmark)

    Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf

    2015-01-01

    , following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface...

  15. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Haanes, K A; Majláth, Zs

    2015-01-01

    induces inflammatory activation in the trigeminal ganglion. METHODS: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7...

  16. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia

    DEFF Research Database (Denmark)

    Zakrzewska, Joanna M; Palmer, Joanne; Morisset, Valerie

    2017-01-01

    BACKGROUND: Current standard of care for trigeminal neuralgia is treatment with the sodium channel blockers carbamazepine and oxcarbazepine, which although effective are associated with poor tolerability and the need for titration. BIIB074, a Nav1.7-selective, state-dependent sodium-channel blocker...

  17. Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.

    Science.gov (United States)

    Ott, V; Benedict, C; Schultes, B; Born, J; Hallschmid, M

    2012-03-01

    In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction. © 2011 Blackwell Publishing Ltd.

  18. Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

    Science.gov (United States)

    Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

    2002-11-01

    Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

  19. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Science.gov (United States)

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-08

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  20. Study of embryotoxic effects of intranasally administred desloratadine on laboratory animals

    Directory of Open Access Journals (Sweden)

    Alekhina Т.А.

    2017-04-01

    Full Text Available The study was conducted to detect possible changes in embryogenesis and negative effects of third generation antihistamine – desloratadine – after intranasal administration of 1.3 mg/m3 and 13.0 mg/m3 of the substance to laboratory animals during their prenatal period. In these circumstances, desloratadine does not cause any significant changes of embryogenesis parameters. Macroscopic examination of the fetus and placenta in animals of experimental groups did not reveal any pathology or physiological deviations from the norm. 13.0 mg/m3 concentration of the drug caused a decrease in the weight of embryos in comparison with control group of animals and physiological data, despite a well developed, without visible pathology, placenta. This neces­sitates an in-depth study of possible teratogenic effects of intranasally administred desloratadine to laboratory animals.

  1. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus

    2017-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future...... vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally...... primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via...

  2. Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes.

    Science.gov (United States)

    Leal, Paulo Roberto Lacerda; Barbier, Charlotte; Hermier, Marc; Souza, Miguel Angelo; Cristino-Filho, Gerardo; Sindou, Marc

    2014-06-01

    The aim of this study was to prospectively evaluate atrophic changes in trigeminal nerves (TGNs) using measurements of volume (V) and cross-sectional area (CSA) from high-resolution 3-T MR images obtained in patients with unilateral trigeminal neuralgia (TN), and to correlate these data with patient and neurovascular compression (NVC) characteristics and with clinical outcomes. Anatomical TGN parameters (V and CSA) were obtained in 50 patients (30 women and 20 men; mean age 56.42 years, range 22-79 years) with classic TN before treatment with microvascular decompression (MVD). Parameters were compared between the symptomatic (ipsilateralTN) and asymptomatic (contralateralTN) sides of the face. Twenty normal control subjects were also included. Two independent observers blinded to the side of pain separately analyzed the images. Measurements of V (from the pons to the entrance of the nerve into Meckel's cave) and CSA (at 5 mm from the entry of the TGN into the pons) for each TGN were performed using imaging software and axial and coronal projections, respectively. These data were correlated with patient characteristics (age, duration of symptoms before MVD, side of pain, sex, and area of pain distribution), NVC characteristics (type of vessel involved in NVC, location of compression along the nerve, site of compression around the circumference of the root, and degree of compression), and clinical outcomes at the 2-year follow-up after surgery. Comparisons were made using Bonferroni's test. Interobserver variability was assessed using the Pearson correlation coefficient. The mean V of the TGN on the ipsilateralTN (60.35 ± 21.74 mm(3)) was significantly smaller (p controls (78.62 ± 24.62 mm(3) and 89.09 ± 14.72 mm(3), respectively). The mean CSA of the TGN on the ipsilateralTN (4.17 ± 1.74 mm(2)) was significantly smaller than those for the contralateralTN and controls (5.41 ± 1.89 mm(2) and 5.64 ± 0.85 mm(2), respectively). The ipsilateralTN with NVC Grade III

  3. Do carbamazepine, gabapentin, or other anticonvulsants exert sufficient radioprotective effects to alter responses from trigeminal neuralgia radiosurgery?

    Science.gov (United States)

    Flickinger, John C; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S; Arai, Yoshio; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas; Flickinger, John C

    2012-07-15

    Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age ≤70 years, and Type 1 typical

  4. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  5. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  6. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    International Nuclear Information System (INIS)

    Flickinger, John C.; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S.; Arai, Yoshio; Niranjan, Ajay; Lunsford, L. Dade; Kondziolka, Douglas; Flickinger, John C.

    2012-01-01

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6–153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with

  7. Long-term outcome in dogs with sinonasal aspergillosis treated with intranasal infusions of enilconazole

    OpenAIRE

    Schuller, S.; Clercx, Cécile

    2007-01-01

    Long-term outcomes (mean 38+/-17 months) were evaluated in 27 dogs with sinonasal aspergillosis after successful medical treatment using intranasal infusions of 1% or 2% enilconazole (1%, n=15; 2%, n=12). Long-term outcomes with both treatment protocols were good, with half of the dogs being asymptomatic throughout the follow-up period. The remaining dogs showed mild clinical signs compatible with chronic rhinitis/sinusitis. These clinical signs were interpreted as chronic lymphoplasmacytic r...

  8. Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review.

    Science.gov (United States)

    Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M

    2017-12-27

    Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M.

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  10. Low dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized 4-way crossover trial with nasal cavity dimension assessment

    OpenAIRE

    Quintana, Daniel; Westlye, Lars Tjelta; Rustan, Øyvind; Tesli, Natalia; Poppy, Claire; Smevik, Hanne; Tesli, Martin Steen; Røine, Marianne; Mahmoud, Ramy; Smerud, Knut Terje; Djupesland, Per G.; Andreassen, Ole Andreas

    2015-01-01

    Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ?Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we ...

  11. Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

    Science.gov (United States)

    Skulberg, Arne Kristian; Tylleskar, Ida; Nilsen, Turid; Skarra, Sissel; Salvesen, Øyvind; Sand, Trond; Loftsson, Thorsteinn; Dale, Ola

    2018-03-22

    This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. clinicaltrials.gov : NCT02307721.

  12. [Targeting the brain through the nose. Effects of intranasally administered insulin].

    Science.gov (United States)

    Brünner, Y F; Benedict, C; Freiherr, J

    2013-08-01

    The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies.

  13. Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

    Science.gov (United States)

    Barik, Sailen

    2009-01-01

    Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

  14. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

    Directory of Open Access Journals (Sweden)

    Surjyanarayan Mandal

    2015-09-01

    Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

  15. Cocoa Enriched Diets Enhance Expression of Phosphatases and Decrease Expression of Inflammatory Molecules in Trigeminal Ganglion Neurons

    Science.gov (United States)

    Cady, Ryan J.; Durham, Paul L.

    2010-01-01

    Activation of trigeminal nerves and release of neuropeptides that promote inflammation are implicated in the underlying pathology of migraine and temporomandibular joint (TMJ) disorders. The overall response of trigeminal nerves to peripheral inflammatory stimuli involves a balance between enzymes that promote inflammation, kinases, and those that restore homeostasis, phosphatases. The goal of this study was to determine the effects of a cocoa-enriched diet on the expression of key inflammatory proteins in trigeminal ganglion neurons under basal and inflammatory conditions. Rats were fed a control diet or an isocaloric diet enriched in cocoa for 14 days prior to an injection of noxious stimuli to cause acute or chronic excitation of trigeminal neurons. In animals fed a cocoa-enriched diet, basal levels of the mitogen-activated kinase (MAP) phosphatases MKP-1 and MKP-3 were elevated in neurons. Importantly, the stimulatory effects of acute or chronic peripheral inflammation on neuronal expression of the MAPK p38 and extracellular signal-regulated kinases (ERK) were significantly repressed in response to cocoa. Similarly, dietary cocoa significantly suppressed basal neuronal expression of calcitonin gene-related peptide (CGRP) as well as stimulated levels of the inducible form of nitric oxide synthase (iNOS), proteins implicated in the underlying pathology of migraine and TMJ disorders. To our knowledge, this is first evidence that a dietary supplement can cause upregulation of MKP, and that cocoa can prevent inflammatory responses in trigeminal ganglion neurons. Furthermore, our data provide evidence that cocoa contains biologically active compounds that would be beneficial in the treatment of migraine and TMJ disorders. PMID:20138852

  16. Trigeminal neuralgia--a prospective systematic study of clinical characteristics in 158 patients

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Gozalov, Aydin; Olesen, Jes

    2014-01-01

     = .043. It affected solely the second and/or third trigeminal branch in 109 (69%) while the first branch alone was affected in only 7 (4%). Notably, 78 (49%) had concomitant persistent pain in addition to paroxysmal stabbing pain. Autonomic symptoms were present in 48 (31%). Patients who had...... not undergone surgery for TN had sensory abnormalities in 35 (29%). CONCLUSIONS: This, the first study in a series of papers focusing on the clinical, radiological, and etiological aspects of TN, revealed that the symptomatology of TN includes a high percentage of concomitant persistent pain, autonomic symptoms......, and sensory abnormalities. These findings offer new insights to the prevailing clinical impression of the clinical characteristics in TN....

  17. [Activity of glial cells in trigeminal nervous system in rats with experimental pulpitis].

    Science.gov (United States)

    Gu, Bin; Liu, Na; Liu, Hongchen

    2014-04-29

    To observe the activity change of astrocyte in related nucleus caused by acute pulpitis in rats. Rat acute pulpitis model was induced by lipopolysaccharides (LPS). And, according to processing time, a total of 30 rats were divided into 5 groups of control, 6, 12, 24 and 48 h. Immunohistochemistry and Western blot were employed to detect the dynamic expression of glial fibrillary acidic protein (GFAP) in spinal nucleus of trigeminal nerve (Vc). The relative gray value of ipsilateral Vc GFAP expression in experimental groups was 153 ± 11 at 12 h. And it significantly increased versus the control group (100 ± 4)(P pulpitis model, activated glial cells are probably involved in the processes of pulpitis and hyperalgesia.

  18. Whole transcriptome expression of trigeminal ganglia compared to dorsal root ganglia in Rattus Norvegicus

    DEFF Research Database (Denmark)

    Kogelman, Lisette Johanna Antonia; Christensen, Rikke Elgaard; Pedersen, Sara Hougaard

    2017-01-01

    The trigeminal ganglia (TG) subserving the head and the dorsal root ganglia (DRG) subserving the rest of the body are homologous handling sensory neurons. Differences exist, as a number of signaling substances cause headache but no pain in the rest of the body. To date, very few genes involved...... in this difference have been identified. We aim to reveal basal gene expression levels in TG and DRG and detect genes that are differentially expressed (DE) between TG and DRG. RNA-Sequencing from six naïve rats describes the whole transcriptome expression profiles of TG and DRG. Differential expression analysis...... was followed by pathway analysis to identify DE processes between TG and DRG. In total, 64 genes had higher and 55 genes had lower expressed levels in TG than DRG. Higher expressed genes, including S1pr5 and Gjc2, have been related to phospholipase activity. The lower expressed genes, including several Hox...

  19. Diagnosis and treatment of trigeminal schwannomas extending into both the middle and posterior cranial fossa

    Institute of Scientific and Technical Information of China (English)

    徐启武; 车晓明; 胡杰; 杨伯捷

    2004-01-01

    @@ Trigeminal schwannomas (TSs) account for 0.1%-0.4% of all intracranial tumors and 1%-8% of intracranial schwannomas.1,2 Yoshida and Kawase3 classified TSs into 6 types according to their locations: M (TS involving the middle cranial fossa), P (TS involving the posterior cranial fossa), E (TS located at extracranial space), MP (TS involving both the middle and the posterior cranial fossa), ME (TS involving the middle cranial fossa and the extracranial space), and MPE (TS involving the the middle and the posterior cranial fossa and the extracranial space). Of these types, MP is the commonest, but is difficult to be totally removed. Between January 1984 and June 2003, we surgically treated 28 patients with TSs of type MP and obtained satisfactory results. To make a correct diagnosis of TS, to select appropriate surgical approach, and to improve surgical outcome of TS of type MP, we analysed the related clinical data and experiences.

  20. Gamma knife radiosurgery for trigeminal neuralgia. Analysis of a multi institutional study

    International Nuclear Information System (INIS)

    Takanashi, Masami; Ozaki, Yoshimaru; Satou, Kenichi; Oikawa, Mitsuteru; Nakamura, Hirohiko; Fukuoka, Seiji

    2013-01-01

    A multi-institutional study was conducted to evaluate the results of gamma knife radiosurgery (GKRS) for the treatment of trigeminal neuralgia. Eleven hundred and thirty-five patients at 39 centers were analyzed. Three hundred and sixty-nine patients had undergone percutaneous nerve block and 173 patients had undergone microvascular decompression (MVD) prior to GKRS. GKRS was performed for 69.4% of patients targeted at the nerve root entry zone (REZ) and for 20.4% of patients targeted at the retrogasserian region (RGR). The target dose of the GKRS used in the current study varied from 70 to 90 Gy (mean: 77.8 Gy). The median follow-up period after GKRS was 21.1 months (range 1 to 125 months). Six hundred and eighty-nine patients (66%) responded with excellent or good control (pain free), 157 (15%) obtained fair control (more than 50% relief), and 192 (19%) experienced treatment failure. After 3 years, 64% of cases were pain free and 80% had more than 50% pain relief. After 4 years, 37 patients underwent additional GKRS, 36 MVD and 36 percutaneous nerve block. Tolerable hypoesthesia or paresthesia occurred in 129 patients (11%), whereas bothersome symptoms developed in 8 patients (1%). But no patient developed deafferentation pain. Nine patients (1%) complained of dry eye, but no other abnormalities of the cornea and conjunctiva were found on ophthalmological examination. Higher maximum radiosurgical dose was associated with a significantly greater factor of complete pain relief (p=0.0101). GKRS is a safe and effective alternative treatment for trigeminal neuralgia, and is a minimally invasive treatment. In addition it provided benefit to a patient population unwilling or unable to undergo more invasive surgical approaches. (author)

  1. Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder.

    Science.gov (United States)

    Cook, Ian A; Abrams, Michelle; Leuchter, Andrew F

    2016-04-01

    External stimulation of the trigeminal nerve (eTNS) is an emerging neuromodulation therapy for epilepsy and depression. Preliminary studies suggest it has an excellent safety profile and is associated with significant improvements in seizures and mood. Neuroanatomical projections of the trigeminal system suggest eTNS may alter activity in structures regulating mood, anxiety, and sleep. In this proof-of-concept trial, the effects of eTNS were evaluated in adults with posttraumatic stress disorder (PTSD) and comorbid unipolar major depressive disorder (MDD) as an adjunct to pharmacotherapy for these commonly co-occurring conditions. Twelve adults with PTSD and MDD were studied in an eight-week open outpatient trial (age 52.8 [13.7 sd], 8F:4M). Stimulation was applied to the supraorbital and supratrochlear nerves for eight hours each night as an adjunct to pharmacotherapy. Changes in symptoms were monitored using the PTSD Patient Checklist (PCL), Hamilton Depression Rating Scale (HDRS-17), Quick Inventory of Depressive Symptomatology (QIDS-C), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Over the eight weeks, eTNS treatment was associated with significant decreases in PCL (p = 0.003; median decrease of 15 points; effect size d 1.5), HDRS-17 (p depression severity were achieved in the eight weeks of acute eTNS treatment. This novel approach to wearable brain stimulation may have use as an adjunct to pharmacotherapy in these disorders if efficacy and tolerability are confirmed with additional studies. © 2016 International Neuromodulation Society.

  2. Central syntropic effects elicited by trigeminal proprioceptive equilibrium in Alzheimer’s disease: a case report

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    De Cicco Vincenzo

    2012-06-01

    Full Text Available Abstract Introduction The presented patient, affected by Alzheimer’s disease, underwent neuropsychological evaluation and functional magnetic resonance imaging investigation under occlusal proprioceptive un-balance and re-balance conditions. Saccadic and pupillometric video-oculographic examinations were performed in order to detect connected trigeminal proprioceptive motor patterns able to interfere with reticular formation cerebellum functions linked to visual and procedural processes prematurely altered in Alzheimer’s disease. Case presentation A 66-year-old Caucasian man, affected by Alzheimer’s disease and with a neuropsychological evaluation issued by the Alzheimer’s Evaluation Unit, underwent an electromyographic investigation of the masseter muscles in order to assess their functional balance. The patient showed a bilateral lack of all inferior molars. The extreme myoelectric asymmetry in dental occlusion suggested the rebalancing of masseter muscular functions through concurrent transcutaneous stimulation of the trigeminal nerve supramandibular and submandibular motor branches. The above-mentioned method allows detection of symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch, called orthotic-syntropic bite. A few days later, the patient underwent a new neuropsychological investigation, together with a functional magnetic resonance imaging study, and saccadic, pupillometric video-oculographic examinations in occlusal un-balance and re-balance conditions. Conclusions Comparative data analysis has shown that a re-balanced occlusal condition can improve a patient’s cognitive-attentive functions. Moreover, the saccadic and pupillometric video-oculographic investigations have proven useful both in analyzing reticulo-cerebellar subcortical systems, prematurely altered in Alzheimer’s disease, and in implementing neurological evaluations.

  3. Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

    Science.gov (United States)

    de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

    2017-11-15

    The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1 H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Usefulness of a Virtual Reality Percutaneous Trigeminal Rhizotomy Simulator in Neurosurgical Training.

    Science.gov (United States)

    Shakur, Sophia F; Luciano, Cristian J; Kania, Patrick; Roitberg, Ben Z; Banerjee, P Pat; Slavin, Konstantin V; Sorenson, Jeffrey; Charbel, Fady T; Alaraj, Ali

    2015-09-01

    Simulation-based training may be incorporated into neurosurgery in the future. To assess the usefulness of a novel haptics-based virtual reality percutaneous trigeminal rhizotomy simulator. A real-time augmented reality simulator for percutaneous trigeminal rhizotomy was developed using the ImmersiveTouch platform. Ninety-two neurosurgery residents tested the simulator at American Association of Neurological Surgeons Top Gun 2014. Postgraduate year (PGY), number of fluoroscopy shots, the distance from the ideal entry point, and the distance from the ideal target were recorded by the system during each simulation session. Final performance score was calculated considering the number of fluoroscopy shots and distances from entry and target points (a lower score is better). The impact of PGY level on residents' performance was analyzed. Seventy-one residents provided their PGY-level and simulator performance data; 38% were senior residents and 62% were junior residents. The mean distance from the entry point (9.4 mm vs 12.6 mm, P = .01), the distance from the target (12.0 mm vs 15.2 mm, P = .16), and final score (31.1 vs 37.7, P = .02) were lower in senior than in junior residents. The mean number of fluoroscopy shots (9.8 vs 10.0, P = .88) was similar in these 2 groups. Linear regression analysis showed that increasing PGY level is significantly associated with a decreased distance from the ideal entry point (P = .001), a shorter distance from target (P = .05), a better final score (P = .007), but not number of fluoroscopy shots (P = .52). Because technical performance of percutaneous rhizotomy increases with training, we proposed that the skills in performing the procedure in our virtual reality model would also increase with PGY level, if our simulator models the actual procedure. Our results confirm this hypothesis and demonstrate construct validity.

  5. Neuronavigator-guided percutaneous radiofrequency thermocoagulation in the treatment of intractable trigeminal neuralgia.

    Science.gov (United States)

    Xu, Shu-jun; Zhang, Wen-hua; Chen, Teng; Wu, Cheng-yuan; Zhou, Mao-de

    2006-09-20

    Percutaneous radiofrequency thermocoagulation of the trigeminal ganglion (PRTTG) is regarded as the first choice for most patients with trigeminal neuralgia (TN) because of its safety and feasibility. However, neuronavigator-guided PRTTG has been seldom reported. The purpose of this study was to assess the safety and efficacy of neuronavigator-guided PRTTG for the treatment of intractable TN. Between January 2000 and December 2004, 54 patients with intractable TN were enrolled into this study and were randomly divided into two groups. The patients in navigation group (n = 26) underwent PRTTG with frameless neuronavigation, and those in control group (n = 28) received PRTTG without neuronavigation. Three months after the operation, the efficacy, side effects, and complications of the surgery were recorded. The patients in the control group were followed up for 10 to 54 months (mean, 34 +/- 5), and those in the navigation group were followed up for 13 to 58 months (mean, 36 +/- 7). Kaplan-Meier analyses of the pain-free survival curves were used for the censored survival data, and the log-rank test was used to compare survival curves of the two groups. The immediate complete pain-relief rate of the navigation group was 100%, whereas it was 95% in the control. The proportion of sustained pain-relief rates at 12, 24 and 36 months after the procedure were 85%, 77%, and 62% in the navigation group, and 54%, 40%, and 35% in the control. Recurrences in the control group were more common than that in the navigation group. Annual recurrence rate in the first and second years were 15% and 23% in the navigation group, and 46%, 60% in the control group. No side-effect and complication was noted in the navigation group except minimal facial hypesthesia. Neuronavigator-guided PRTTG is a safe and promising method for treatment of intractable TN with better short- and long-term outcomes and lower complication rate than PRTTG without neuronavigation.

  6. Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

    Science.gov (United States)

    Phan, Jack; Pollard, Courtney; Brown, Paul D; Guha-Thakurta, Nandita; Garden, Adam S; Rosenthal, David I; Fuller, Clifton D; Frank, Steven J; Gunn, G Brandon; Morrison, William H; Ho, Jennifer C; Li, Jing; Ghia, Amol J; Yang, James N; Luo, Dershan; Wang, He C; Su, Shirley Y; Raza, Shaan M; Gidley, Paul W; Hanna, Ehab Y; DeMonte, Franco

    2018-04-27

    OBJECTIVE The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. METHODS From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. RESULTS Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p control.

  7. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Wang Y

    2015-10-01

    Full Text Available Yanping Wang,1,2 Xiaoling Zhang,2 Qiaobing Guan,2 Lihong Wan,2 Yahui Yi,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 2Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, Zhejiang Province, People’s Republic of China Abstract: The pathophysiology of idiopathic trigeminal neuralgia (ITN has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected. Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002. Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. Keywords: trigeminal neuralgia, resting fMRI, brain, chronic pain, local connectivity

  8. Outcome of radiosurgery treatment with a linear accelerator in patients with trigeminal neuralgia.

    Science.gov (United States)

    Cordero Tous, N; Cruz Sabido, J de la; Román Cutillas, A M; Saura Rojas, E J; Jorques Infante, A M; Olivares Granados, G

    2017-04-01

    An overview of the effectiveness of radiosurgery in patients diagnosed with trigeminal neuralgia with an analysis of potential predictors of good outcome. All patients treated with linear accelerator radiosurgery between 2004 and 2011 were analysed. A dose of 60Gy dose was administered 1 to 2mm from the root entry zone with a maximum isodose of 20% delivered to the brainstem. Clinical results for pain control and any side effects were analysed at 12 and 36 months (BNI score). The study included 71 patients (mean follow-up 50.5 months). Pain improvement at 12 months was observed in 68.11% of the total (28.98% with BNI score i-ii; 39.12% with BNI score iii) and at 36 months in 58.21% (23.88% BNI score i-ii; 34.32% BNI score iii). Average recovery time was 3.69 months and the relapse rate was 44.68%. Patients with typical pain displayed statistically significant differences in improvement rates at 12 and at 36 months (P<047 and P<.002). Onset of improvement was analysed using Kaplan-Meyer plots. Statistically significant differences were observed between patients with typical and atypical pain at 36 months (P<.012) in Kaplan-Meyer plots. Side effects were recorded in 15 patients (20.89%), including 9 cases of facial numbness (13.43%); only 2 cases were clinically relevant (2.98%). According to our results, radiosurgery is an effective treatment for trigeminal neuralgia, with few side effects. Typical pain seems to be a good predictor of pain relief. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Magnetic resonance imaging of vascular compression in trigeminal neuralgia and hemifacial spasms

    International Nuclear Information System (INIS)

    Nagaseki, Yoshishige; Horikoshi, Tohru; Omata, Tomohiro; Sugita, Masao; Nukui, Hideaki; Sakamoto, Hajime; Kumagai, Hiroshi; Sasaki, Hideo; Tsuji, Reizou.

    1991-01-01

    We show how neurosurgical planning can benefit from the better visualization of the precise vascular compression of the nerve provided by the oblique-sagittal and gradient-echo method (OS-GR image) using magnetic resonance images (MRI). The scans of 3 patients with trigeminal neuralgia (TN) and of 15 with hemifacial spasm (HFS) were analyzed for the presence and appearance of the vascular compression of the nerves. Imaging sequences consisted of an OS-GR image (TR/TE: 200/20, 3-mm-thick slice) cut along each nerve shown by the axial view, which was scanned at the angle of 105 degrees taken between the dorsal line of the brain stem and the line corresponding to the pontomedullary junction. In the OS-GR images of the TN's, the vascular compressions of the root entry zone (REZ) of the trigeminal nerve were well visualized as high-intensity lines in the 2 cases whose vessels were confirmed intraoperatively. In the other case, with atypical facial pain, vascular compression was confirmed at the rostral distal site on the fifth nerve, apart from the REZ. In the 15 cases of HFS, twelve OS-GR images (80%) demonstrated vascular compressions at the REZ of the facial nerves from the direction of the caudoventral side. During the surgery for these 12 cases, in 11 cases (excepting the 1 case whose facial nerve was not compressed by any vessels), vascular compressions were confirmed corresponding to the findings of the OS-GR images. Among the 10 OS-GR images on the non-affected side, two false-positive findings were visualized. It is concluded that OS-GR images obtained by means of MRI may serve as a useful planning aid prior to microvascular decompression for cases of TN and HFS. (author)

  10. Microvascularization in trigeminal ganglion of the common tree shrew (Tupaia glis).

    Science.gov (United States)

    Kongstaponkit, S; Pradidarcheep, W; Toutip, S; Chunhabundit, P; Somana, R

    1997-01-01

    Since there is only a limited number of studies of the blood supply to the trigeminal ganglion (TG) in mammalian species, the TG from 16 common tree shrews (Tupaia glis) were investigated by light microscope, transmission electron microscope (TEM) and the corrosion cast technique in conjunction with scanning electron microscope (SEM). It was found that the TG contained clusters of neurons in the peripheral region whereas the bundles of nerve fibers were located more centrally. Each ganglionic neuron had a concentric nucleus and was ensheathed by satellite cells. It was noted that blood vessels of a continuous type were predominantly found in the area where the neurons were densely located and were much less frequently observed in the area occupied by nerve fibers. With TEM, the TG was shown to be mainly associated with large neurons containing big nuclei and prominent nucleoli. The blood supply of the TG is derived from the most rostral branch of the pontine artery, from the stapedial artery or sometimes from the supraorbital artery, and from the accessory meningeal artery which is a branch of the maxillary artery passing through the foramen ovale. These arteries give off branches and become capillary networks in the ganglion before draining blood to the peripheral region. The veins at the medial border drained into the cavernous sinus directly or through the inferior hypophyseal vein, while those at the lateral side of the ganglion carried the blood into the pterygoid plexus via an accessory meningeal vein. The veins along the trigeminal nerve root joined the posterior part of the cavernous sinus. These studies establish a unique anatomical distribution of the TG blood supply in the tree shrew and the utility of the cast/SEM technique in discerning detailed features of the blood supply in the nervous system.

  11. Computed tomography-guided percutaneous ozone injection of the Gasserian ganglion for the treatment of trigeminal neuralgia

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    An JX

    2018-01-01

    Full Text Available Jian-Xiong An,1,2 Hui Liu,1 Ruo-Wen Chen,1,2 Yong Wang,1 Wen-Xing Zhao,1 Derek Eastwood,3 John P Williams4 1Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University & Beijing Institute of Translational Medicine, Chinese Academy of Sciences, 2Department of Anesthesiology, Weifang Medical University, Beijing, People’s Republic of China; 3Department of Pain Services, Wirral University Teaching Hospital, Wirral, Merseyside, UK; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The aim of this study was to evaluate the therapeutic effect of computed tomography (CT-guided percutaneous ozone injection for refractory trigeminal neuralgia. Design: A retrospective evaluation was performed in the study. Setting: The study was conducted at a university hospital pain center. Patients and methods: A total of 29 patients with a clinical diagnosis of refractory trigeminal neuralgia were enrolled. All patients were treated with a percutaneous ozone injection and one patient was excluded. There were 21 patients with classical trigeminal neuralgia (group A and seven patients with painful trigeminal neuropathy caused by post-herpetic neuralgia (group B. The percutaneous injection was an oxygen–ozone mixture at an ozone concentration of 30 mg/­mL into the Gasserian ganglion performed under CT guidance. The number of ­procedures performed varied from one to as many as 16. Outcomes were evaluated using visual analog scale (VAS pain scores. Results: The combined VAS scores were 7.11 ± 1.23 pretreatment, 2.86 ± 1.69 posttreatment (P < 0.05 and 3.25 ± 2.01 after 6-month follow-up (P < 0.05. In group A, the VAS scores were 7.10 ± 1.04 pretreatment and 2.90 ± 1.84 posttreatment (P < 0.05. In group B, the VAS scores were 7.14 ± 1.77 pretreatment and 2.71 ± 1.25 posttreatment (P < 0.05. After 6-months follow-up, the VAS score was 3.38

  12. Assessment of neurovascular compression in patients with trigeminal neuralgia with a boundary fusion three-dimensional magnetic resonance cisternogram/angiogram

    International Nuclear Information System (INIS)

    Satoh, Toru; Omi, Megumi; Ohsako, Chika; Onoda, Keisuke; Date, Isao

    2007-01-01

    Precise assessment of the complex nerve-vessel relationship at the root entry zone (REZ) of the trigeminal nerve is useful for the planning of the microvascular decompression (MVD) in patients with trigeminal neuralgia. We have applied a boundary imaging of fusion three-dimensional (3D) magnetic resonance (MR) cisternogram/angiogram. The boundary imaging allows virtual assessment of the spatial relationship of the neurovascular compression at the REZ of the trigeminal nerve. The boundary images depicted complex anatomical relationship of the offending vessels to the trigeminal nerve REZ. The presence of offending vessels, compressive site, and degree of neurovascular compression were assessed from various viewpoints in the cistern and virtually through the brainstem and trigeminal nerve per se. The 3D visualization of the nerve-vessel relationship with fusion images was consistent with the intraoperative findings. The boundary fusion 3D MR cisternogram/angiogram may prove a useful adjunct for the diagnosis and decision-marking process to execute the MVD in patients with trigeminal neuralgia. (author)

  13. Epidermoid cyst in the cerebellopontine angle cistern presenting as trigeminal neuralgia. Diagnostic values of the orbicularis oculi reflex and metrizamide CT cisternography - case report -

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Takashi; Goya, Tomokazu; Kinoshita, Kazuo (Miyazaki Medical College, Miyazaki (Japan)); Fukui, Masashi

    1983-05-01

    This 29-year-old male had been suffering from left trigeminal neuralgia one year prior to admission. Admission was prompted by the development of pain in the third division of the left trigeminal nerve. Physical and neurological examinations were not remarkable except for the facial pain. The orbicularis oculi reflex showed delayed latency of R/sub 1/ on the affected side. CT scans performed pre- and post-contrast enhancement revealed a low density area in the left cerebellopontine angle cistern. Metrizamide CT cisternography clearly revealed the margin of the lesion as the contrast media did not enter into the low density area. A left suboccipital craniectomy was performed. The trigeminal nerve was surrounded by a thin-capsulated mass and cholesteatoma materials. Histological diagnosis was epidermoid cyst. Since this surgical procedure, the trigeminal neuralgia has not recurred for one year. Without objective neurological deficits, it is difficult to distinguish symptomatic trigeminal from idiopathic neuralgia. Therefore, minor change of the orbicularis oculi reflex should help in objectively detecting dysfunction of the trigeminal nerve. Metrizamide CT cisternography is also useful in diagnosis of cystic lesions.

  14. Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.

    Science.gov (United States)

    Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

    2018-01-02

    Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing. To overcome these problems of RHT, microemulsion (ME) and mucoadhesive microemulsion (MME) of RHT were formulated for brain targeting via intranasal delivery route and compared on the basis of in vivo pharmacokinetics. ME and MME formulations containing RHT were developed by water titration method. Characterization of ME and MME was done for various physicochemical parameters, nasal spray pattern, and in vivo pharmacokinetics quantitatively and qualitatively (gamma scintigraphy studies). The developed ME and MME were transparent having globule size approximately in the range of 53-55 nm. Pharmacokinetic studies showed higher values for C max and DTP for intranasal RHT: CH-ME over RHT-ME, thus indicating the effect of chitosan in modulating tight junctions, thereby enhanced paracellular transport of RHT. Gamma scintigraphy and in vivo pharmacokinetic study suggested enhanced RHT concentration, upon intranasal administration of RHT:CH-ME, compare with other groups administered formulations intranasally. These findings suggested the potential of non-invasive intranasal route for brain delivery, especially for therapeutics, facing challenges in oral administration.

  15. Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

    Directory of Open Access Journals (Sweden)

    Tracy A Nichols

    Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

  16. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

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    Honglei Chen

    Full Text Available Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI. However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran intranasally.For the mouse model of direct ALI, lipopolysaccharide (LPS was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model.In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  17. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    Science.gov (United States)

    Chen, Honglei; Wu, Shaoping; Lu, Rong; Zhang, Yong-guo; Zheng, Yuanyuan; Sun, Jun

    2014-01-01

    Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally. For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model. In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  18. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Mans, Christoph; Guzman, David Sanchez-Migallon; Lahner, Lesanna L; Paul-Murphy, Joanne; Sladky, Kurt K

    2012-09-01

    Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and effects on cloacal temperature, respiratory rate, and heart rate in manually restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9) were administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint in a complete crossover study. Respiratory rate and sedation scores were recorded before and during capture and during and after 15 minutes of manual restraint. Heart rate and cloacal temperature were recorded during manual restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and the recovery time was recorded. In those birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight, and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects to intranasal midazolam and flumazenil administration were observed. Further studies on the safety of intranasal midazolam and flumazenil in this species are warranted.

  19. Proposal for evaluating the quality of reports of surgical interventions in the treatment of trigeminal neuralgia: the Surgical Trigeminal Neuralgia Score.

    Science.gov (United States)

    Akram, Harith; Mirza, Bilal; Kitchen, Neil; Zakrzewska, Joanna M

    2013-09-01

    The aim of this study was to design a checklist with a scoring system for reporting on studies of surgical interventions for trigeminal neuralgia (TN) and to validate it by a review of the recent literature. A checklist with a scoring system, the Surgical Trigeminal Neuralgia Score (STNS), was devised partially based on the validated STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria and customized for TN after a literature review and then applied to a series of articles. These articles were identified using a prespecified MEDLINE and Embase search covering the period from 2008 to 2010. Of the 584 articles found, 59 were studies of interventional procedures for TN that fulfilled the inclusion criteria and 56 could be obtained in full. The STNS was then applied independently by 3 of the authors. The maximum STNS came to 30, and was reliable and reproducible when used by the 3 authors who performed the scoring. The range of scores was 6-23.5, with a mean of 14 for all the journals. The impact factor scores of the journals in which the papers were published ranged from 0 to 4.8. Twenty-four of the studies were published in the Journal of Neurosurgery or in Neurosurgery. Studies published in neurosurgical journals ranked higher on the STNS scale than those published in nonneurosurgical journals. There was no statistically significant correlation between STNS and impact factors. Stereotactic radiosurgery (n = 25) and microvascular decompression (n = 15) were the most commonly reported procedures. The diagnostic criteria were stated in 35% of the studies, and 4 studies reported subtypes of TN. An increasing number of studies (46%) used the recommended Kaplan-Meier methodology for pain survival outcomes. The follow-up period was unclear in 8 studies, and 26 reported follow-ups of more than 5 years. Complications were reported fairly consistently but the temporal course was not always indicated. Direct interview, telephone conversation

  20. A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: moderation by method and mental health.

    Science.gov (United States)

    Cardoso, Christopher; Kingdon, Danielle; Ellenbogen, Mark A

    2014-11-01

    A large body of research has examined the acute effects of intranasal oxytocin administration on social cognition and stress-regulation. While progress has been made with respect to understanding the effect of oxytocin administration on social cognition in clinical populations (e.g. autism, schizophrenia), less is known about its impact on the functioning of the hypothalamic-pituitary-adrenal (HPA) axis among individuals with a mental disorder. We conducted a meta-analysis on the acute effect of intranasal oxytocin administration on the cortisol response to laboratory tasks. The search yielded eighteen studies employing a randomized, placebo-controlled design (k=18, N=675). Random-effects models and moderator analyses were performed using the metafor package for the statistical program R. The overall effect size estimate was modest and not statistically significant (Hedges g=-0.151, p=0.11) with moderate heterogeneity in this effect across studies (I(2)=31%). Controlling for baseline differences in cortisol concentrations, moderation analyses revealed that this effect was larger in response to challenging laboratory tasks that produced a robust stimulation of the HPA-axis (Hedges g=-0.433, 95% CI[-0.841, -0.025]), and in clinical populations relative to healthy controls (Hedges g=-0.742, 95% CI[-1.405, -0.078]). Overall, oxytocin administration showed greater attenuation of the cortisol response to laboratory tasks that strongly activated the HPA-axis, relative to tasks that did not. The effect was more robust among clinical populations, suggesting possible increased sensitivity to oxytocin among those with a clinical diagnosis and concomitant social difficulties. These data support the view that oxytocin may play an important role in HPA dysfunction associated with psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion

    Directory of Open Access Journals (Sweden)

    Patwardhan Amol M

    2005-01-01

    results illustrate that NGF, GDNF and BDNF differentially alter TG sensory neuron survival, neurochemical properties and TRPV1-mediated neuropeptide release in culture. In particular, our findings suggest that GDNF and NGF differentially modulate TRPV1-mediated neuropeptide secretion sensitivity, with NGF having a much greater effect on a per neuron basis than GDNF. These findings are discussed in relation to possible therapeutic roles for growth factors or their modulators in pathological pain states, especially as these relate to the trigeminal system.

  2. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    Science.gov (United States)

    2012-01-01

    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  3. Persistent trigeminal artery/persistent trigeminal artery variant and coexisting variants of the head and neck vessels diagnosed using 3 T MRA

    International Nuclear Information System (INIS)

    Bai, M.; Guo, Q.; Li, S.

    2013-01-01

    Aim: To report the prevalence and characteristic features of persistent trigeminal artery (PTA), PTA variant (PTAV), and other variants of the head and neck vessels, identified using magnetic resonance angiography (MRA). Materials and methods: The three-dimensional (3D) time of flight (TOF) MRA and 3D contrast-enhanced (CE) MRA images of 6095 consecutive patients who underwent 3 T MRA at Liaocheng People's Hospital from 1 September 2008 through 31 May 2012 were retrospectively reviewed and analysed. Thirty-two patients were excluded because of suboptimal image quality or internal carotid artery (ICA) occlusion. Results: The prevalence of both PTA and PTAV was 0.63% (PTA, 26 cases; PTAV, 12 cases). The prevalence of coexisting variants of the head and neck vessels in cases of PTA/PTAV was 52.6% (20 of 38 cases). The vascular variants that coexisted with cases of PTA/PTAV were as follows: the intracranial arteries varied in 10 cases, the origin of the supra-aortic arteries varied in nine cases, the vertebral artery (VA) varied in 14 cases, and six cases displayed fenestrations. Fifteen of the 20 cases contained more than two types of variants. Conclusion: The prevalence of both PTA and PTAV was 0.63%. Although PTA and PTAV are rare vascular variants, they frequently coexist with other variants of the head and neck vessels. Multiple vascular variations can coexist in a single patient. Recognizing PTA, PTAV, and other variants of the head and neck vessels is crucial when planning a neuroradiological intervention or surgery. Recognizing the medial PTA is very important in clinical practice when performing trans-sphenoidal surgery on the pituitary as failure to do so could result in massive haemorrhage

  4. Quantitative sensory testing in classical trigeminal neuralgia-a blinded study in patients with and without concomitant persistent pain

    DEFF Research Database (Denmark)

    Younis, Samaira; Maarbjerg, Stine; Reimer, Maren

    2016-01-01

    The diagnostic criteria of the third International Classification of Headache Disorders state that there should be no neurological deficits in patients with classical trigeminal neuralgia (TN) at clinical examination. However, studies demonstrating sensory abnormalities at bedside examination in TN...... scores were calculated to process frequency analyses and Z-profiles. We found increased mechanical detection threshold on the symptomatic side (47.2% vs 0%, P = 0.008), asymptomatic side (33.3% vs 0%, P = 0.011), and hand (36% vs 0%, P ... increased mechanical detection threshold on the symptomatic side compared with the asymptomatic side (-2.980 vs -2.166, P = 0.040). Thermal and mechanical hyperalgesia was detected bilaterally in the face and the hand. Trigeminal neuralgia patients with concomitant persistent pain tended to have higher mean...

  5. Neuronal vacuolation of the trigeminal nuclei in goats caused by ingestion of Prosopis juliflora pods (mesquite beans).

    Science.gov (United States)

    Tabosa, I M; Souza, J C; Graça, D L; Barbosa-Filho, J M; Almeida, R N; Riet-Correa, F

    2000-06-01

    Three groups of 6 goats each were fed a ration containing 30, 60, or 90%, on a dry matter base, of Prosopis juliflora pods. A control group of 4 goats ingested only the basic ration. Two hundred and ten days after the start of the experiment 3 goats that ingested 60% pods in and 4 that ingested 90% had mandibular tremors, mainly during chewing. All animals were killed after 270 d of ingestion. No gross lesions were observed. Histologic lesions were characterized by fine vacuolation of the pericaryon of neurons from the trigeminal nuclei. Occasionally neurons of the oculomotor nuclei were also affected. Wallerian degeneration was occasionally observed in the mandibular and trigeminal nerves. Denervation atrophy of the masseter, temporal, hypoglossus, genioglossus, styloglossus, medial pterygoid and lateral pterygoid muscles was seen. The clinical signs from feeding the P juliflora pods were caused by a selective toxicity to neurons of some cranial nerve nuclei.

  6. Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review.

    Science.gov (United States)

    Siemerink, Martin J; Freling, Nicole J M; Saeed, Peerooz

    2017-10-01

    Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemia.

  7. Oral steroids alone or followed by intranasal steroids versus watchful waiting in the management of otitis media with effusion.

    Science.gov (United States)

    Hussein, A; Fathy, H; Amin, S M; Elsisy, N

    2017-10-01

    To evaluate the effects of oral steroids alone or followed by intranasal steroids versus watchful waiting on the resolution of otitis media with effusion in children aged 2-11 years. A total of 290 children with bilateral otitis media with effusion were assigned to 3 groups: group A was treated with oral steroids followed by intranasal steroids, group B was treated with oral steroids alone and group C was managed with watchful waiting. Patients were evaluated with audiometry and tympanometry. The complete resolution rates of otitis media with effusion were higher in groups A and B than in group C at six weeks. There were no significant differences in otitis media with effusion resolution rates between the groups at three, six and nine months. Oral steroids lead only to a quick resolution of otitis media with effusion, with no long-term benefits. There was no benefit of using intranasal steroids in the management of otitis media with effusion.

  8. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  9. The acute effects of intranasal oxytocin administration on endocrine and sexual function in males.

    Science.gov (United States)

    Burri, Andrea; Heinrichs, Markus; Schedlowski, Manfred; Kruger, Tillmann H C

    2008-06-01

    The role of the neuropeptide oxytocin (OT) ranges from the modulation of neuroendocrine physiological effects to the establishment of complex social and bonding behaviours. Experimental studies in animals, as well as case reports in humans, suggest that OT affects different aspects of sexual behaviour and has predominantly facilitating properties for sexual appetence and performance. Using a previously established experimental paradigm of sexual arousal and masturbation-induced orgasm, this study investigated the acute effects of intranasal OT application (24I.U.) on endocrine parameters and measures of sexual appetence and function in healthy men (n=10). In a double-blind, placebo-controlled, balanced cross-over design, sexual arousal, and orgasm were induced by an erotic film and masturbation. In addition to the continuous recording of endocrine (OT, cortisol, prolactin, epinephrine, norepinephrine) and cardiovascular data (heart rate), parameters of appetitive, consummatory, and refractory sexual behaviour were assessed using the acute sexual experience scale (ASES). OT plasma levels were significantly elevated after intranasal OT throughout the whole experiment (>60 min). In addition, OT treatment induced significantly higher increases in epinephrine plasma levels during sexual activity without affecting cortisol levels, prolactin levels or heart rate. OT treatment did not alter appetitive, consummatory, and refractory sexual behaviour according to the ASES. However, when subjects were asked about their subjective perception of whether OT or placebo had been applied, eight out of 10 subjects in the OT group answered correctly, thus pointing to an altered perception of arousal. In conclusion, intranasally administered OT leads to a marked increase in OT plasma levels together with increased secretion of catecholamines when subjects are engaged in sexual activity in a laboratory setting. As the effects of OT on sexual behaviour were equivocal, future studies

  10. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    Energy Technology Data Exchange (ETDEWEB)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa, E-mail: etyszkiewicz@wum.edu.pl

    2012-11-15

    The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  11. Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

    Science.gov (United States)

    Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

    2017-02-15

    Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

    Directory of Open Access Journals (Sweden)

    H Najminezhad

    2013-01-01

    Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

  13. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

    International Nuclear Information System (INIS)

    O'Brien, R.T.; Evans, S.M.; Wortman, J.A.; Hendrick, M.J.

    1996-01-01

    Objective: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Design: Retrospective study. Animals: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Procedure: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Results: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Clinical Implications: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia

  14. Intranasal delivery of E-selectin reduces atherosclerosis in ApoE-/- mice.

    Directory of Open Access Journals (Sweden)

    Xinhui Li

    Full Text Available Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to (pre-tolerization or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.

  15. Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

    Directory of Open Access Journals (Sweden)

    Asher Maroof

    2014-01-01

    Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

  16. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    International Nuclear Information System (INIS)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa

    2012-01-01

    The effect of intranasal manganese chloride (MnCl 2 ·4H 2 O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl 2 ·4H 2 O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  17. Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis.

    Science.gov (United States)

    Broggi, G; Ferroli, P; Franzini, A; Servello, D; Dones, I

    2000-01-01

    To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24 months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.

  18. Patterns of neurovascular compression in patients with classic trigeminal neuralgia: A high-resolution MRI-based study

    International Nuclear Information System (INIS)

    Lorenzoni, José; David, Philippe; Levivier, Marc

    2012-01-01

    Purpose: To describe the anatomical characteristics and patterns of neurovascular compression in patients suffering classic trigeminal neuralgia (CTN), using high-resolution magnetic resonance imaging (MRI). Materials and methods: The analysis of the anatomy of the trigeminal nerve, brain stem and the vascular structures related to this nerve was made in 100 consecutive patients treated with a Gamma Knife radiosurgery for CTN between December 1999 and September 2004. MRI studies (T1, T1 enhanced and T2-SPIR) with axial, coronal and sagital simultaneous visualization were dynamically assessed using the software GammaPlan™. Three-dimensional reconstructions were also developed in some representative cases. Results: In 93 patients (93%), there were one or several vascular structures in contact, either, with the trigeminal nerve, or close to its origin in the pons. The superior cerebellar artery was involved in 71 cases (76%). Other vessels identified were the antero-inferior cerebellar artery, the basilar artery, the vertebral artery, and some venous structures. Vascular compression was found anywhere along the trigeminal nerve. The mean distance between the nerve compression and the origin of the nerve in the brainstem was 3.76 ± 2.9 mm (range 0–9.8 mm). In 39 patients (42%), the vascular compression was located proximally and in 42 (45%) the compression was located distally. Nerve dislocation or distortion by the vessel was observed in 30 cases (32%). Conclusions: The findings of this study are similar to those reported in surgical and autopsy series. This non-invasive MRI-based approach could be useful for diagnostic and therapeutic decisions in CTN, and it could help to understand its pathogenesis.

  19. Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.

    Science.gov (United States)

    Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf; Edvinsson, Lars

    2015-01-01

    Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.

  20. Dynamic Regulation of Delta-Opioid Receptor in Rat Trigeminal Ganglion Neurons by Lipopolysaccharide-induced Acute Pulpitis.

    Science.gov (United States)

    Huang, Jin; Lv, Yiheng; Fu, Yunjie; Ren, Lili; Wang, Pan; Liu, Baozhu; Huang, Keqiang; Bi, Jing

    2015-12-01

    Delta-opioid receptor (DOR) and its endogenous ligands distribute in trigeminal system and play a very important role in modulating peripheral inflammatory pain. DOR activation can trigger p44/42 mitogen-activated protein kinase (ERK1/2) and Akt signaling pathways, which participate in anti-inflammatory and neuroprotective effects. In this study, our purpose was to determine the dynamic changes of DOR in trigeminal ganglion (TG) neurons during the process of acute dental pulp inflammation and elucidate its possible mechanism. Forty rats were used to generate lipopolysaccharide-induced acute pulpitis animal models at 6, 12, and 24 hours and sham-operated groups. Acute pulpitis was confirmed by hematoxylin-eosin staining, and TG neuron activation was determined by anti-c-Fos immunohistochemistry. DOR protein and gene expression in TG was investigated by immunohistochemistry, Western blotting, and real-time polymerase chain reaction, and DOR expression in trigeminal nerves and dental pulp was also determined by immunohistochemistry. To further investigate the mechanism of DOR modulating acute inflammation, the change of pErk1/2 and pAkt in TG was examined by immunohistochemistry. Lipopolysaccharide could successfully induce acute pulpitis and activated TG neurons. Acute pulpitis could dynamically increase DOR protein and gene expression at 6, 12, and 24 hours in TG, and DOR dimerization was significantly increased at 12 and 24 hours. Acute pulpitis also induced the dynamic change of DOR protein in trigeminal nerve and dental pulp. Furthermore, ERK1/2 and Akt signaling pathways were inhibited in TG after acute pulpitis. Increased DOR expression and dimerization may play important roles in peripheral acute inflammatory pain. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  1. A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma

    OpenAIRE

    Frisardi, Gianni; Iani, Cesare; Sau, Gianfranco; Frisardi, Flavio; Leornadis, Carlo; Lumbau, Aurea; Enrico, Paolo; Sirca, Donatella; Staderini, Enrico Maria; Chessa, Giacomo

    2013-01-01

    Background: In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Methods: Electrophysiological studies included bilateral electrical transcrania...

  2. A Proposed Neurologic Pathway for Scalp Acupuncture: Trigeminal Nerve-Meninges-Cerebrospinal Fluid-Contacting Neurons-Brain.

    Science.gov (United States)

    Wang, Shuya; Liu, Kun; Wang, Yuan; Wang, Shuyou; He, Xun; Cui, Xiang; Gao, Xinyan; Zhu, Bing

    2017-10-01

    Objective: Scalp acupuncture is a somatic stimulation therapy that produces prominent clinical effects when used to treat cerebral diseases. However, this acupuncture's therapeutic mechanisms have not yet been well-addressed. Scalp acupoints are innervated by the trigeminal nerve, which is coincident with the intracranial sensory afferents as well as with the meningeal vessels. In recent years, cerebrospinal fluid-contacting neurons have been found and proved to transmit allergic substances between brain the parenchyma and meninges, representing a possible network between scalp acupuncture and the brain. The aim of the current study was to observe the connections between scalp acupoints and the meninges and to establish a possible mechanism for scalp acupuncture. Materials and Methods: Twenty-five adult Sprague-Dawley rats were used for the present study. Evans Blue dye (Sigma Chemical Co, St. Louis, MO) was injected though each rat's caudal vein after trigeminal stimulation for plasma extravasation observation. Cerebral blood flow (CBF) values of the rat's brain surface were measured at different timepoints before and after electroacupuncture (EA) on GB 15 ( Toulinqi ) or ST 36 ( Zusanli ). Results: These preliminary studies indicated that neurogenic plasma extravasation on a rat's skin and dura mater after mechanical or electrical stimulation of the trigeminal nerves is a reliable way to show the pathologic connection between scalp acupoints and the meninges. Moreover, CBF of the rat's brain surface is increased significantly after EA stimulation at GB 15 ( Toulinqi ), which is located in the receptive field of the supraorbital nerve. Conclusions: These findings suggest that the mechanism of scalp acupuncture might lie in the specific neurologic pathway that could be termed as trigeminal nerve-meninges-cerebrospinal fluid-contacting neurons-brain , which is a possible shortcut to brain functional regulation and cerebral disease treatment.

  3. [Linear accelerator-based stereotactic radiosurgery for the treatment of trigeminal neuralgia. Nine years' experience in a single institution].

    Science.gov (United States)

    Serrano-Rubio, A A; Martinez-Manrique, J J; Revuelta-Gutierrez, R; Gomez-Amador, J L; Martinez-Anda, J J; Ponce-Gomez, J A; Moreno-Jimenez, S

    2014-09-16

    INTRODUCTION. Pharmacological treatment is the first therapeutic step towards controlling pain in trigeminal neuralgia, but 25-50% of patients become medication resistant. There are currently several surgical alternatives for treating these patients. AIM. To evaluate the effectiveness and safety of stereotactic radiosurgery for the treatment of patients with trigeminal neuralgia. PATIENTS AND METHODS. A follow-up study was conducted on 30 patients who underwent radiosurgery using a Novalis linear accelerator. Eighty per cent of the dosage was calculated at the isocentre, the entry zone of the root of the trigeminal nerve. The mean follow-up time was 27.5 months (range: 1-65 months). RESULTS. The mean age was 66 years (range: 36-87 years), with a time to progression of 7.1 years (range: 4-27 years). The distribution of the pain was from the right side (63.3%). Of the 30 patients, 27 experienced an improvement (90%) 1.6 months (range: 1 week-4 months) after the treatment; 10 patients (33.3%) scored grade I, and 17 patients (56.6%) obtained a score of grade II. During the follow-up, four patients (14.2%) suffered a relapse; two underwent re-irradiation. Time without recurrence was 62.7 months (range: 54.6-70.8 months). The rate of side effects was 76.7% and only three patients developed facial anaesthesia with loss of the corneal reflex. CONCLUSIONS. The use of the linear accelerator is an effective therapeutic option in the treatment of trigeminal neuralgia, since it provides adequate long-term control of the pain, reduces the use of medication and improves the quality of life.

  4. The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

    Science.gov (United States)

    Greene, R K; Spanos, M; Alderman, C; Walsh, E; Bizzell, J; Mosner, M G; Kinard, J L; Stuber, G D; Chandrasekhar, T; Politte, L C; Sikich, L; Dichter, G S

    2018-03-27

    Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed

  5. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

    Science.gov (United States)

    Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

    2014-02-01

    Evidence suggests that intranasal oxytocin enhances the perception of emotion in facial expressions during standard emotion identification tasks. However, it is not clear whether this effect is desirable in people who do not show deficits in emotion perception. That is, a heightened perception of emotion in faces could lead to "oversensitivity" to the emotions of others in nonclinical participants. The goal of this study was to assess the effects of intranasal oxytocin on emotion perception using ecologically valid social and nonsocial visual tasks. Eighty-two participants (42 women) self-administered a 24 IU dose of intranasal oxytocin or a placebo in a double-blind, randomized experiment and then completed the perceiving and understanding emotion components of the Mayer-Salovey-Caruso Emotional Intelligence Test. In this test, emotion identification accuracy is based on agreement with a normative sample. As expected, participants administered intranasal oxytocin rated emotion in facial stimuli as expressing greater emotional intensity than those given a placebo. Consequently, accurate identification of emotion in faces, based on agreement with a normative sample, was impaired in the oxytocin group relative to placebo. No such effect was observed for tests using nonsocial stimuli. The results are consistent with the hypothesis that intranasal oxytocin enhances the salience of social stimuli in the environment, but not nonsocial stimuli. The present findings support a growing literature showing that the effects of intranasal oxytocin on social cognition can be negative under certain circumstances, in this case promoting "oversensitivity" to emotion in faces in healthy people. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  6. Men perform comparably to women in a perspective taking task after administration of intranasal oxytocin but not after placebo.

    Directory of Open Access Journals (Sweden)

    Angeliki eTheodoridou

    2013-05-01

    Full Text Available Oxytocin (OT is thought to play an important role in human interpersonal information processing and behavior. By inference, OT should facilitate empathic responding, i.e. the ability to feel for others and to take their perspective. In two independent double-blind, placebo-controlled between-subjects studies, we assessed the effect of intranasally administered OT on affective empathy and perspective taking, whilst also examining potential sex differences (e.g., women being more empathic than men. In study 1, we provided 96 participants (48 men with an empathy scenario and recorded self reports of empathic reactions to the scenario, while in study 2, a sample of 120 individuals (60 men performed a computerized implicit perspective taking task. Whilst results from Study 1 showed no influence of OT on affective empathy, we found in Study 2 that OT exerted an effect on perspective taking ability in men. More specifically, men responded faster than women in the placebo group but they responded as slowly as women in the OT group. We conjecture that men in the OT group adopted a social perspective taking strategy, such as did women in both groups, but not men in the placebo group. On the basis of results across both studies, we suggest that self-report measures (such as used in Study 1 might be less sensitive to OT effects than more implicit measures of empathy such as that used in Study 2. If these assumptions are confirmed, one could infer that OT effects on empathic responses are more pronounced in men than women, and that any such effect is best studied using more implicit measures of empathy rather than explicit self-report measures.

  7. Bi-modal radiofrequency treatment for coexisting neuralgia and neuropathy in adjacent divisions of the trigeminal nerve.

    Science.gov (United States)

    Bhatjiwale, M; Bhatjiwale, M; Naik, L D; Chopade, P

    2018-05-29

    Trigeminal neuralgia and deafferentation neuropathic pain, or trigeminal neuropathy, are different symptomatologies, rarely reported to present together. The case of a 65-year-old gentleman suffering from trigeminal neuralgia of the maxillary and mandibular division is reported. He first underwent an infraorbital neurectomy that was complicated by deafferentation neuropathic pain, whilst his mandibular neuralgia continued. He was treated successfully for both the neuropathic and neuralgic symptoms in the same session using ultra-extended euthermic pulsed radiofrequency treatment for the maxillary division (V2) and radiofrequency thermocoagulation for the mandibular division (V3). This report is novel in describing the use of dual modalities in the same session for two distinct coexisting clinical entities in two different divisions of the same cranial nerve. The use of ultra-extended pulsed radiofrequency treatment for neuropathic pain in this case is also unique. Nearly 2years after the procedure, the patient continues to have complete pain relief. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Nitric oxide synthase (NOS) in the trigeminal vascular system and other brain structures related to pain in rats

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Ploug, Kenneth Beri; Hay-Schmidt, Anders

    2010-01-01

    to measure the respective levels of mRNA and protein for nNOS and eNOS in peripheral and central tissues involved in migraine pain: dura mater, pial arteries, trigeminal ganglion (TG) trigeminal nucleus caudalis (TNC), periaqueductal grey (PAG), thalamus, hypothalamus, cortex, pituitary gland, hippocampus...... and cerebellum. iNOS was excluded from the present study because it was not induced. In the trigeminal vascular system we found the highest expression of nNOS mRNA in pial arteries. However, protein expression of nNOS was maximum in TNC. Among other brain structures, nNOS mRNA and protein expression...... was remarkably higher in the cerebellum than in any other tissues. Regarding eNOS in the trigeminovascular system, the highest mRNA expression was found in pial arteries. In the other brain structures, eNOS mRNA expression was similar but with lowest mRNA concentration in the pituitary gland and the highest...

  9. Effects of NSAIDs on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Trigeminal Ganglia

    Directory of Open Access Journals (Sweden)

    Vittorio Vellani

    2017-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to treat migraine, but the mechanisms of their effects in this pathology are not fully elucidated. The trigeminal ganglia and calcitonin gene-related peptide (CGRP have been implicated in the pathophysiology of migraine. The release of CGRP and prostaglandin E2 (PGE2 from freshly isolated rat trigeminal ganglia was evaluated after oral administration of nimesulide, etoricoxib, and ketoprofen, NSAIDs with different pharmacological features. Thirty minutes after oral administration, nimesulide, 10 mg/Kg, decreased the GCRP release induced by an inflammatory soup, while the other NSAIDs were ineffective at this point in time. Two hours after oral nimesulide (5 and 10 mg/Kg and ketoprofen (10 mg/Kg, but not of etoricoxib, a significant decrease in the CGRP release was observed. All drugs reduced PGE2, although with some differences in timing and doses, and the action on CGRP does not seem to be related to PGE2 inhibition. The reduction of CGRP release from rat trigeminal ganglia after nimesulide and ketoprofen may help to explain the mechanism of action of NSAIDs in migraine. Since at 30 minutes only nimesulide was effective in reducing CGRP release, these results suggest that this NSAID may exert a particularly rapid effect in patients with migraine.

  10. Occlusal splint versus modified nociceptive trigeminal inhibition splint in bruxism therapy: a randomized, controlled trial using surface electromyography.

    Science.gov (United States)

    Dalewski, B; Chruściel-Nogalska, M; Frączak, B

    2015-12-01

    An occlusal splint and a modified nociceptive trigeminal inhibition splint (AMPS, anterior deprogrammer, Kois deprogrammer, Lucia jig, etc.) are commonly and quite frequently used in the treatment of masticatory muscle disorders, although their sustainable and long-lasting effect on these muscles' function is still not very well known. Results of scant surface electromyography studies in patients with temporomandibular disorders have been contradictory. The aim of this study was to evaluate both devices in bruxism therapy; EMG activity levels during postural activity and maximum voluntary contraction of the superficial temporal and masseter muscles were compared before and after 30 days of treatment. Surface electromyography of the examined muscles was performed in two groups of bruxers (15 patients each). Patients in the first group used occlusal splints, while those in the second used modified nociceptive trigeminal inhibition splints. The trial was randomized, controlled and semi-blind. Neither device affected the asymmetry index or postural activity/maximum voluntary contraction ratio after 1 month of treatment. Neither the occlusal nor the nociceptive trigeminal inhibition splint showed any significant influence on the examined muscles. Different scientific methods should be considered in clinical applications that require either direct influence on the muscles' bioelectrical activity or a quantitative measurement of the treatment quality. © 2015 Australian Dental Association.

  11. Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal Biting Force in Npr2-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Gohar Ter-Avetisyan

    2018-06-01

    Full Text Available Bifurcation of axons from dorsal root ganglion (DRG and cranial sensory ganglion (CSG neurons is mediated by a cGMP-dependent signaling pathway composed of the ligand C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2 and the cGMP-dependent protein kinase I (cGKI. Here, we demonstrate that mesencephalic trigeminal neurons (MTN which are the only somatosensory neurons whose cell bodies are located within the CNS co-express Npr2 and cGKI. Afferents of MTNs form Y-shaped branches in rhombomere 2 where the ligand CNP is expressed. Analyzing mouse mutants deficient for CNP or Npr2 we found that in the absence of CNP-induced cGMP signaling MTN afferents no longer bifurcate and instead extend either into the trigeminal root or caudally in the hindbrain. Since MTNs provide sensory information from jaw closing muscles and periodontal ligaments we measured the bite force of conditional mouse mutants of Npr2 (Npr2flox/flox;Engr1Cre that lack bifurcation of MTN whereas the bifurcation of trigeminal afferents is normal. Our study revealed that the maximal biting force of both sexes is reduced in Npr2flox/flox;Engr1Cre mice as compared to their Npr2flox/flox littermate controls. In conclusion sensory feedback mechanisms from jaw closing muscles or periodontal ligaments might be impaired in the absence of MTN axon bifurcation.

  12. Trigeminofacial reflex: a means of detecting proximity to ophthalmic and maxillary divisions of the trigeminal nerve during surgery.

    Science.gov (United States)

    AlMasri, Omar A; Brown, Emma E; Forster, Alan; Kamel, Mahmoud H

    2014-11-01

    The aim in this paper was to localize and detect incipient damage to the ophthalmic and maxillary branches of the trigeminal nerve during tumor surgery. This was an observational study of patients with skull base, retroorbital, or cavernous sinus tumors warranting dissection toward the cavernous sinus at a university hospital. Stimuli were applied as normal during approach to the cavernous sinus to localize cranial nerves (CNs) III, IV, and VI. Recordings were also obtained from the facial muscles to localize CN VII. The trigeminofacial reflex was sought simply by observing a longer time base routinely. Clear facial electromyography responses were reproduced when stimuli were applied to the region of V1, V2, and V3. Response latency was increased compared with direct CN VII stimuli seen in some cases. Responses gave early warning of approach to these sensory trigeminal branches. The authors submit this as a new technique, which may improve the chances of preserving trigeminal sensory branches during surgery in this region.

  13. Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? a prospective double-blind, randomized study

    International Nuclear Information System (INIS)

    Flickinger, John C.; Pollock, Bruce E.; Kondziolka, Douglas; Phuong, Loi K.; Foote, Robert L.; Stafford, Scott L.; Lunsford, L. Dade

    2001-01-01

    Purpose: To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief. Methods and Materials: Eighty-seven patients with typical trigeminal neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n=44) or two (n=43) isocenters. The median follow-up was 26 months (range 1-36). Results: Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7%±5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p=0.23). Improved pain relief correlated with younger age (p=0.025) and fewer prior procedures (p=0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p=0.018). Conclusions: Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications

  14. Spatial–temporal signature of resting-state BOLD signals in classic trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-12-01

    Full Text Available Yanping Wang,1 Congying Xu,1 Liping Zhai,1 Xudong Lu,1 Xiaoqiang Wu,1 Yahui Yi,2 Ziyun Liu,1 Qiaobing Guan,1 Xiaoling Zhang1 1Department of Neurology, the Second Hospital of Jiaxing City, Jiaxing, Zhejiang, 2Department of Radiology, the Second Hospital of Jiaxing City, Jiaxing, Zhejiang, China Abstract: Resting-state functional magnetic resonance imaging (R-fMRI signals are spatiotemporally organized. R-fMRI studies in patients with classic trigeminal neuralgia (CTN have suggested alterations in functional connectivity. However, far less attention has been given to investigations of the local oscillations and their frequency-specific changes in these patients. The objective of this study was to address this issue in patients with CTN. R-fMRI data from 17 patients with CTN and 19 age- and gender-matched healthy controls (HCs were analyzed using amplitude of low-frequency fluctuation (ALFF. The ALFF was computed across different frequencies (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz in patients with CTN compared to HCs. In the typical band, patients with CTN showed increases of ALFF in bilateral temporal, occipital, and left middle frontal regions and in the left middle cingulate gyrus, as well as decreases of ALFF in the right inferior temporal region and in regions (medial prefrontal regions of default mode network. These significant group differences were identified in different sub-bands, with greater brainstem findings in higher frequencies (slow-4 and extensive default mode network and right postparietal results in lower frequencies (slow-5. Furthermore, significant relationships were found between subjective pain ratings and both amplitudes of higher frequency (slow-4 blood oxygen level-dependent (BOLD signals in pain localization brain regions and lower frequencies (slow-5 in pain signaling/modulating brain regions in the patients, and decreased ALFF within the prefrontal regions was significantly

  15. Therapeutic cranial nerve irradiation: results from a multi-center dose response study of radiosurgery for trigeminal neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Kondziolka, D; Flickinger, J; Lunsford, L D; Young, R; Vermeulen, S; Duma, C; Jacques, D B; Rand, R; Regis, J; Peragut, J C; Epstein, M H; Lindquist, C

    1995-07-01

    Purpose/Objective: We performed a multi-institution study to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. We hypothesized that MRI-stereotactic targeting of the trigeminal nerve and irradiation with a single 4 mm isocenter, 2-4 mm anterior to the brainstem, could be a safe and effective treatment for this disorder. Materials and Methods: Fifty patients at five centers had radiosurgery using a single 4 mm isocenter targeted at the root entry zone. All patients had typical trigeminal neuralgia. The mean patient age was 70 years, (range, 40-87). Thirty-two patients had undergone prior surgery, and the mean number of procedures performed was 2.8 (range, 1-7). Eighteen patients (36%) had not had prior surgery before radiosurgery. Maximum radiosurgery doses included 60 Gy (n=8), 65 Gy (n=3), 70 Gy (n=27), 75 Gy (n=2), 80 Gy (n=6) and 90 Gy (n=4). All patients were discharged within 24 hours and were studied in regard to the degree of pain relief, latency interval to pain relief, sensory loss, and the need for further therapy. Mean follow-up after radiosurgery was 9.2 months (range, 2-26 months). Results: At last follow-up, 25 patients (50%) had excellent control (pain-free), 17 (34%) had good control (50-90% relief), and 8 (16%) had failed (see Figure). The median time to pain relief was one month. We identified an actuarial response rate of 53% for complete pain relief at seven months, and 93% for pain reduction (50-100% relief). At 18 months, these results declined to 48% and 77% respectively. A significantly greater proportion of patients receiving a radiosurgery maximum dose of {>=} 70 Gy achieved complete pain relief (63% vs. 18%) and >50% pain reduction (96% vs. 80%) than those with doses <70 Gy. Patients without prior surgery had significantly better outcomes in univariate testing. Three patients (6%) developed increased facial paresthesiae after radiosurgery

  16. Therapeutic cranial nerve irradiation: results from a multi-center dose response study of radiosurgery for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Kondziolka, D.; Flickinger, J.; Lunsford, L.D.; Young, R.; Vermeulen, S.; Duma, C.; Jacques, D.B.; Rand, R.; Regis, J.; Peragut, J.C.; Epstein, M.H.; Lindquist, C.

    1995-01-01

    Purpose/Objective: We performed a multi-institution study to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. We hypothesized that MRI-stereotactic targeting of the trigeminal nerve and irradiation with a single 4 mm isocenter, 2-4 mm anterior to the brainstem, could be a safe and effective treatment for this disorder. Materials and Methods: Fifty patients at five centers had radiosurgery using a single 4 mm isocenter targeted at the root entry zone. All patients had typical trigeminal neuralgia. The mean patient age was 70 years, (range, 40-87). Thirty-two patients had undergone prior surgery, and the mean number of procedures performed was 2.8 (range, 1-7). Eighteen patients (36%) had not had prior surgery before radiosurgery. Maximum radiosurgery doses included 60 Gy (n=8), 65 Gy (n=3), 70 Gy (n=27), 75 Gy (n=2), 80 Gy (n=6) and 90 Gy (n=4). All patients were discharged within 24 hours and were studied in regard to the degree of pain relief, latency interval to pain relief, sensory loss, and the need for further therapy. Mean follow-up after radiosurgery was 9.2 months (range, 2-26 months). Results: At last follow-up, 25 patients (50%) had excellent control (pain-free), 17 (34%) had good control (50-90% relief), and 8 (16%) had failed (see Figure). The median time to pain relief was one month. We identified an actuarial response rate of 53% for complete pain relief at seven months, and 93% for pain reduction (50-100% relief). At 18 months, these results declined to 48% and 77% respectively. A significantly greater proportion of patients receiving a radiosurgery maximum dose of ≥ 70 Gy achieved complete pain relief (63% vs. 18%) and >50% pain reduction (96% vs. 80%) than those with doses <70 Gy. Patients without prior surgery had significantly better outcomes in univariate testing. Three patients (6%) developed increased facial paresthesiae after radiosurgery

  17. Distinctive features of Phox2b-expressing neurons in the rat reticular formation dorsal to the trigeminal motor nucleus.

    Science.gov (United States)

    Nagoya, Kouta; Nakamura, Shiro; Ikeda, Keiko; Onimaru, Hiroshi; Yoshida, Atsushi; Nakayama, Kiyomi; Mochizuki, Ayako; Kiyomoto, Masaaki; Sato, Fumihiko; Kawakami, Kiyoshi; Takahashi, Koji; Inoue, Tomio

    2017-09-01

    Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b + ) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b + RdV neurons is still unclear. We investigated the physiological and morphological properties of Phox2b + RdV neurons using postnatal day 2-7 transgenic rats expressing yellow fluorescent protein under the control of Phox2b. Almost all of Phox2b + RdV neurons were glutamatergic, whereas Phox2b-negative (Phox2b - ) RdV neurons consisted of a few glutamatergic, many GABAergic, and many glycinergic neurons. The majority (48/56) of Phox2b + neurons showed low-frequency firing (LF), while most of Phox2b - neurons (35/42) exhibited high-frequency firing (HF) in response to intracellularly injected currents. All, but one, Phox2b + neurons (55/56) did not fire spontaneously, whereas three-fourths of the Phox2b - neurons (31/42) were spontaneously active. K + channel and persistent Na + current blockers affected the firing of LF and HF neurons. The majority of Phox2b + (35/46) and half of the Phox2b - neurons (19/40) did not respond to stimulations of the mesencephalic trigeminal nucleus, the trigeminal tract, and the principal sensory trigeminal nucleus. Biocytin labeling revealed that about half of the Phox2b + (5/12) and Phox2b - RdV neurons (5/10) send their axons to the trigeminal motor nucleus. These results suggest that Phox2b + RdV neurons have distinct neurotransmitter phenotypes and firing properties from Phox2b - RdV neurons and might play important roles in feeding-related functions including suckling and possibly mastication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

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    Hetal P Thakkar

    2014-01-01

    Full Text Available Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400 was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710% after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674% and finally by mirtazapine solution (17.63 ± 0.612%.

  19. Combined immunomodulating effects of BCG and Lentinan after intranasal application in guinea pigs.

    Science.gov (United States)

    Drandarska, Ivanka; Kussovski, Vesselin; Nikolaeva, Sascha; Markova, Nadya

    2005-04-01

    The ability of a Shiitake (Lentinus edodes) medical mushroom-derived bioactive polymer Lentinan (Ajinomoto, Japan) to modulate the immune response makes it a potential candidate for combination therapy with BCG, or as adjunct for BCG vaccination, especially in high-risk individuals. We studied the combined immune-potential effectiveness of intranasal application of Lentinan (at a dose of 1 mg/kg, three times at 2-day intervals), followed by administration of BCG (strain Sofia SL-222 at a dose of 1 x 10(8) CFU, once) in guinea pigs. Samples of broncho-alveolar lavage fluid, as well as tissue fragments of lungs, spleens and lymph nodes were obtained from four groups (combined treatment with Lentinan and BCG; only with Lentinan; only with BCG; control with saline) of animals at different intervals--1, 14 and 45 days after last treatment and were evaluated by several parameters (establishing the number, H2O2 and nitrite production, and killing ability against Mycobacterium tuberculosis and Staphylococcus aureus of alveolar macrophages; spleen index, BCG CFU in spleens and histomorphological observations). Our attention was focused both on local effects in lungs, and systematical effects in reticuloendothelial system. The results indicate that intranasal application of BCG alone, or in combination with Lentinan induced high level of alveolar macrophage activation. Pre-treatment with Lentinan enhanced the local immunohistological response to BCG in lung and reduced the generalized side effects.

  20. Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

    Science.gov (United States)

    Dhuria, Shyeilla V; Fine, Jared M; Bingham, Deborah; Svitak, Aleta L; Burns, Rachel B; Baillargeon, Amanda M; Panter, Scott S; Kazi, Abdul N; Frey, William H; Hanson, Leah R

    2016-08-03

    Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Effects of intranasal oxytocin on the attentional bias to emotional stimuli in patients with bulimia nervosa.

    Science.gov (United States)

    Kim, Youl-Ri; Eom, Jin-Sup; Leppanen, Jenni; Leslie, Monica; Treasure, Janet

    2018-05-01

    Bulimia nervosa (BN) is characterized by binge eating and emotional dysregulation including increased negative affectivity (anger, anxiety). The aim of this study was to examine the effect of oxytocin on attentional processes towards anger in patients with BN. The study design consisted of a double-blind, placebo-controlled within-subject crossover, single dose experiment. Sixty-four women (31 patients with BN and 33 healthy comparisons) completed self-reported measures to evaluate emotional difficulties and were administered a single dose of intranasal oxytocin (40IU) or placebo followed by a visual probe detection task to examine attentional orienting to angry or happy faces. Patients with BN reported higher emotional dysregulation and more difficulties in controlling anger compared to the healthy comparison group. Patients with BN and the healthy women exhibited similar attentional bias to angry faces in the placebo condition. Intranasal oxytocin reduced the attentional bias towards angry faces in both the BN patients and the healthy women. We found that a single dose of oxytocin reduced vigilance towards angry faces in patients with BN as well as healthy women. The results showed that patients with BN are not different from healthy women in terms of vigilance towards threat. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice.

    Science.gov (United States)

    Wei, Zheng Zachory; Zhang, James Ya; Taylor, Tammi M; Gu, Xiaohuan; Zhao, Yingying; Wei, Ling

    2018-03-01

    Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.

  3. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

    Science.gov (United States)

    Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

    2016-09-20

    Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

    Science.gov (United States)

    Dahlem, Chin Hwa Y; Horstman, Molly J; Williams, Brent C

    2016-01-01

    To describe the development, implementation, and preliminary evaluation of Opioid Overdose Response Protocol using intranasal (IN) naloxone in a homeless shelter. Opioid Overdose Response Protocol and training curriculum were developed using the Massachusetts Department of Public Health Opioid Overdose Education and Naloxone Distribution (OEND) flow chart, the American Heart Association (AHA) simplified adult basic life support algorithm, and resources through Harms Reduction Coalition. Intranasal naloxone offers a safe and effective method for opioid reversal. To combat the rising incidence of opioid overdose, IN naloxone should be made available at homeless shelters and other facilities with high frequency of opioid overdose, including the training of appropriate staff. This project has demonstrated the effective training and implementation of an Opioid Overdose Response Protocol, based on feedback received from cardiopulmonary resuscitation (CPR) trained nonhealthcare staff. Nurse practitioners (NPs), with our focus on patient care, prevention, and education, are well suited to the deployment of this life-saving protocol. NPs are in critical positions to integrate opioid overdose prevention education and provide naloxone rescue kits in clinical practices. ©2015 American Association of Nurse Practitioners.

  5. Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

    Science.gov (United States)

    Rando, Jessica; Broering, Derek; Olson, James E; Marco, Catherine; Evans, Stephen B

    2015-09-01

    This study sought to answer the question, "Can police officers administer intranasal naloxone to drug overdose victims to decrease the opioid overdose death rate?" This prospective interventional study was conducted in Lorain County, OH, from January 2011 to October 2014. Starting October 2013, trained police officers administered naloxone to suspected opioid overdose victims through a police officer naloxone prescription program (NPP). Those found by the county coroner to be positive for opioids at the time of death and those who received naloxone from police officers were included in this study. The rate of change in the total number of opioid-related deaths in Lorain County per quarter year, before and after initiation of the NPP, and the trend in the survival rate of overdose victims who were given naloxone were analyzed by linear regression. Significance was established a priori at P police officer NPP with average deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the first 9 months of 2013. After initiation of the police officer NPP, the number of opioid overdose deaths decreased each quarter with an overall average of 13.4. Of the 67 participants who received naloxone by police officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up. Intranasal naloxone administration by police first responders is associated with decreased deaths in opioid overdose victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Improved Intranasal Retentivity and Transnasal Absorption Enhancement by PEGylated Poly-l-ornithine

    Directory of Open Access Journals (Sweden)

    Yusuke Kamiya

    2018-01-01

    Full Text Available We reported that the introduction of polyethylene glycol (PEG to poly-l-ornithine (PLO, which is an homopolymeric basic amino acid having absorption-enhancement ability, prolonged retention time in an in vitro inclined plate test, probably due to an increase in viscosity caused by PEGylation. The aim of the present study is to investigate whether the introduction of PEG chains to PLO improves intranasal retention and transnasal absorption in vivo. We performed intranasal administration experiments using PLO and PEG-PLO with a model drug, fluorescein isothiocyanate dextran (FD-4, in rats under closed and open systems. In the open system, transition of plasma FD-4 concentration after co-administration with unmodified PLO was low, and the area under the plasma concentration-time curve (AUC decreased to about 60% of that in the closed system. In contrast, the AUC after co-administration with PEG-PLO in the open system was about 90% of that in the closed system, and the transition of plasma FD-4 concentration and FD-4 absorption profile were similar to those of the closed system. These findings indicate that introducing PEG chains to homopolymeric basic amino acids (HPBAAs is a very useful method for developing a functional absorption enhancer that can exhibit an efficient in vivo absorption-enhancing effect.

  7. A novel device for delivery of intranasal particulate medication: a pilot study.

    Science.gov (United States)

    Khalili, Sammy; Tkachenko, Natalia; Rotenberg, Brian

    2013-11-01

    Intranasal medication delivery for allergic rhinitis (AR) is considered a mainstay of therapy but is hampered by poor compliance. Among reasons given are unpleasant sensations associated with spray penetration into the pharynx. Our objective was to study a novel method of particle delivery to the nose that would abrogate these issues. This was a double-blind, randomized study. Subjects who met study criteria underwent intranasal particle delivery using a novel device (Trivair Nasal Deposition System; Trimel Pharmaceuticals, Toronto, Canada) that delivered anhydrous lactose particles into the nose via a transoral air puff (thus elevating soft palate and blocking the nasopharynx). Subjects had nostrils randomized into 4 groups (particle sizes 5 μm and 50 μm × doses 12.5 mg and 25 mg). Particle deposition was assessed at 1 minute, 10 minutes, and 30 minutes on the inferior turbinate, middle turbinate, and nasopharynx, respectively, using high-definition endoscopic photography. Each image was compared using an expert blinded 2-person panel for percentage particles remaining. Nonparametric data was assessed using the Wilcoxon signed-rank test via Strata software. Twelve nostrils in total met study criteria. The results showed no difference in effectiveness of nasal particle retention between the groups based on particle size or dose. No particles entered the nasopharynx or oropharynx. This study provides proof-of-principle data that the Trivair Nasal Deposition System is effective at retaining medication in the nose without pharyngeal penetration. Larger studies on this device are warranted. © 2013 ARS-AAOA, LLC.

  8. Effects of Intranasal Oxytocin on Long-Term Memory in Healthy Humans: A Systematic Review.

    Science.gov (United States)

    Brambilla, Michela; Manenti, Rosa; de Girolamo, Giovanni; Adenzato, Mauro; Bocchio-Chiavetto, Luisella; Cotelli, Maria

    2016-12-01

    Preclinical Research The neuropeptide oxytocin (Oxt) is implicated in complex emotional and social behaviors and appears to play an important role in learning and memory. Animal studies have shown that the effects of exogenous Oxt on memory vary according to the timing of administration, context, gender, and dose and may improve the memory of social, but not nonsocial stimuli. Oxt is intimately involved in a broad array of neuropsychiatric functions and may therefore be a pharmacological target for several psychiatric disorders. This review summarizes the potential effects of Oxt on long-term memory processes in healthy humans based on a PubMed search over the period 1980-2016. The effects of intranasal Oxt on human memory are controversial and the studies included in this review have applied a variety of learning paradigms, in turn producing variable outcomes. Specifically, data on the long-term memory of nonemotional stimuli found no effect or even worsening in memory, while studies using emotional stimuli showed an improvement of long-term memory performance. In conclusion, this review identified a link between long-term memory performance and exogenous intranasal Oxt in humans, although these results still warrant further confirmation in large, multicenter randomized controlled trials. Drug Dev Res 77 : 479-488, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

    Directory of Open Access Journals (Sweden)

    Yingying Xu

    2014-07-01

    Full Text Available Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT. Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.

  10. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    Energy Technology Data Exchange (ETDEWEB)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

    2007-06-15

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

  11. Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

    Science.gov (United States)

    Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2013-01-01

    There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

  12. Intranasal bevacizumab in the treatment of HHT -related epistaxis: a systematic review.

    Science.gov (United States)

    Stokes, P; Rimmer, J

    2018-03-01

    Hereditary haemorrhagic telangiectasia (HHT) remains a difficult disease for the ENT specialist to manage. Affected patients often report recurrent epistaxis as the most debilitating symptom. The pathogenesis of the disease is due to genetic mutations affecting angiogenesis. For this reason, the anti-angiogenic therapy bevacizumab has gained popularity in the local treatment of epistaxis in patients with HHT. A systematic review of the efficacy of bevacizumab in local treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, severity and impact on quality of life. A systematic search was performed using the PubMed, MEDLINE and EMBASE databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of intranasal bevacizumab treatment of epistaxis in patients with HHT were included for qualitative analysis. Thirteen studies (four randomised controlled trials, three prospective studies, three retrospective studies, one case series and two case reports) with a total of 357 patients were included. Local administration (either by submucosal injection or topically) did not have a significant impact on epistaxis duration, frequency, severity or quality of life compared to placebo or other local treatments. The available evidence suggests that intranasal bevacizumab treatment does not have a significant effect on epistaxis in patients with HHT. There are several limitations that require further investigation to confidently rule out local bevacizumab as an effective therapy in HHT related epistaxis.

  13. A neurofibromatosis type 2 case with vestibular, trigeminal and facial schwannomas together: magnetic resonance imaging findings

    International Nuclear Information System (INIS)

    Akay, S.; Hamcan, S.; Kara, K.; Battal, B.; Tasar, M.

    2012-01-01

    Full text: Introduction: Neurofibromatosis type 2 (NF2) is characterized by the development of multiple nervous system tumors. This disorder is also called multiple inherited schwannomas (MIS), meningiomas (M), and ependymomas (E) (MISME) syndrome. Objectives and tasks: To discuss the magnetic resonance (MR) imaging findings of a NF2 case who has bilateral vestibular and trigeminal schwannomas, unilateral facial schwannoma, multiple meningiomas and cervical intramedullary spinal cord tumors. Materials and methods: A 23-year-old male patient complaining of tinnitus and imbalance for 3 years, came to Neck-Nose-Throat department of our hospital. After the physical examination, the patient was referred to our department for the further work up with MR imaging. Results: Brain MR imaging showed bilateral acoustic schwannoma which reach through the internal acoustic canals. Bilateral symmetric homogeneously enhanced masses were also detected in Meckel's caves. Similarly, one milimetric enhancing lesion was seen at the right facial nerve. Eight meningiomas in various locations were observed, as well. Additionally, two enhancing intramedullary well-defined small foci were detected in the proximal cervical spinal cord. Ependymomas or intraparanchimal schwannomas were primarily suspected. Conclusion: This case includes all the probable intracranial and spinal mass lesions which may be associated with NF2. Enhanced MR is very reliable imaging modality for the detailed evaluation of NF2 patients

  14. Clinical Outcomes of Gamma Knife Radiosurgery in the Treatment of Patients with Trigeminal Neuralgia

    Science.gov (United States)

    Elaimy, Ameer L.; Hanson, Peter W.; Lamoreaux, Wayne T.; Mackay, Alexander R.; Demakas, John J.; Fairbanks, Robert K.; Cooke, Barton S.; Thumma, Sudheer R.; Lee, Christopher M.

    2012-01-01

    Since its introduction by Leksell, Gamma Knife radiosurgery (GKRS) has become increasingly popular as a management approach for patients diagnosed with trigeminal neuralgia (TN). For this reason, we performed a modern review of the literature analyzing the efficacy of GKRS in the treatment of patients who suffer from TN. For patients with medically refractory forms of the condition, GKRS has proven to be an effective initial and repeat treatment option. Cumulative research suggests that patients treated a single time with GKRS exhibit similar levels of facial pain control when compared to patients treated multiple times with GKRS. However, patients treated on multiple occasions with GKRS are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with GKRS. Although numerous articles have reported MVD to be superior to GKRS in achieving facial pain relief, the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and cannot be considered conclusive. Questions remain regarding optimal GKRS dosing and targeting strategies, which warrants further investigation into this controversial matter. PMID:22229034

  15. Activation of Satellite Glial Cells in Rat Trigeminal Ganglion after Upper Molar Extraction

    International Nuclear Information System (INIS)

    Gunjigake, Kaori K.; Goto, Tetsuya; Nakao, Kayoko; Kobayashi, Shigeru; Yamaguchi, Kazunori

    2009-01-01

    The neurons in the trigeminal ganglion (TG) are surrounded by satellite glial cells (SGCs), which passively support the function of the neurons, but little is known about the interactions between SGCs and TG neurons after peripheral nerve injury. To examine the effect of nerve injury on SGCs, we investigated the activation of SGCs after neuronal damage due to the extraction of the upper molars in rats. Three, 7, and 10 days after extraction, animals were fixed and the TG was removed. Cryosections of the ganglia were immunostained with antibodies against glial fibrillary acidic protein (GFAP), a marker of activated SGCs, and ATF3, a marker of damaged neurons. After tooth extraction, the number of ATF3-immunoreactive (IR) neurons enclosed by GFAP-IR SGCs had increased in a time-dependent manner in the maxillary nerve region of the TG. Although ATF3-IR neurons were not detected in the mandibular nerve region, the number of GFAP-IR SGCs increased in both the maxillary and mandibular nerve regions. Our results suggest that peripheral nerve injury affects the activation of TG neurons and the SGCs around the injured neurons. Moreover, our data suggest the existence of a neuronal interaction between maxillary and mandibular neurons via SGC activation

  16. Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: A pilot study

    Directory of Open Access Journals (Sweden)

    DosSantos Marcos

    2012-09-01

    Full Text Available Abstract Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional μ-opioid receptor (μOR availability in vivo (non-displaceable binding potential BPND of TNP patients with positron emission tomography (PET using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc, an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

  17. Peripheral Neuropathic Facial/Trigeminal Pain and RANTES/CCL5 in Jawbone Cavitation

    Directory of Open Access Journals (Sweden)

    Johann Lechner

    2015-01-01

    Full Text Available Introduction. In this study, we elucidate the possible causative role of chronic subclinical inflammation in jawbone of patients with atypical facial pain (AFP and trigeminal neuralgia (TRN in the local overexpression of the chemokine regulated on activation and normal T-cell expressed and secreted (RANTES/C-C motif ligand 5 CCL5. Neurons contain opioid receptors that transmit antipain reactions in the peripheral and central nervous system. Proinflammatory chemokines like RANTES/CCL5 desensitize μ-opioid receptors in the periphery sensory neurons and it has been suggested that RANTES modifies the nociceptive reaction. Materials and Methods. In 15 patients with AFP/TRN, we examined fatty degenerated jawbone (FDOJ samples for the expression of seven cytokines by multiplex analysis and compared these results with healthy jawbones. Results. Each of these medullary jawbone samples exhibited RANTES as the only highly overexpressed cytokine. The FDOJ cohort with AFP/TRN showed a mean 30-fold overexpression of RANTES compared to healthy jawbones. Conclusions. To the best of our knowledge, no other research has identified RANTES overexpression in silent inflamed jawbones as a possible cause for AFP/TRN. Thus, we hypothesize that the surgical clearing of FDOJ might diminish RANTES signaling pathways in neurons and contribute to resolving chronic neurological pain in AFP/TRN patients.

  18. Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

    Science.gov (United States)

    Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

    2018-03-24

    Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

  19. A neurofibromatosis type 2 case with vestibular, trigeminal and facial schwannomas together: magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Akay, S; Hamcan, S; Kara, K; Battal, B; Tasar, M

    2012-07-01

    Full text: Introduction: Neurofibromatosis type 2 (NF2) is characterized by the development of multiple nervous system tumors. This disorder is also called multiple inherited schwannomas (MIS), meningiomas (M), and ependymomas (E) (MISME) syndrome. Objectives and tasks: To discuss the magnetic resonance (MR) imaging findings of a NF2 case who has bilateral vestibular and trigeminal schwannomas, unilateral facial schwannoma, multiple meningiomas and cervical intramedullary spinal cord tumors. Materials and methods: A 23-year-old male patient complaining of tinnitus and imbalance for 3 years, came to Neck-Nose-Throat department of our hospital. After the physical examination, the patient was referred to our department for the further work up with MR imaging. Results: Brain MR imaging showed bilateral acoustic schwannoma which reach through the internal acoustic canals. Bilateral symmetric homogeneously enhanced masses were also detected in Meckel's caves. Similarly, one milimetric enhancing lesion was seen at the right facial nerve. Eight meningiomas in various locations were observed, as well. Additionally, two enhancing intramedullary well-defined small foci were detected in the proximal cervical spinal cord. Ependymomas or intraparanchimal schwannomas were primarily suspected. Conclusion: This case includes all the probable intracranial and spinal mass lesions which may be associated with NF2. Enhanced MR is very reliable imaging modality for the detailed evaluation of NF2 patients.

  20. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

    Science.gov (United States)

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.

  1. Frame and frameless linear accelerator-based radiosurgery for idiopathic trigeminal neuralgia.

    Science.gov (United States)

    Chen, Allan Y; Hsieh, Yen; McNair, Steffanie; Li, Qijuan; Xu, Kevin Y; Pappas, Conrad

    2015-01-01

    We report outcome of linear accelerator (Linac)-based stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) utilizing rigid head frame (RF) and facemask (FM) immobilization.Method: From November 2008 to October 2012, 48 patients with idiopathic TGN underwent primary SRS by a dedicated Linac. RF immobilization was utilized for 34 patients, and frameless image-guided radiosurgery (IGRS) with FM immobilization was performed in 14 patients. Treatment outcome was assessed by patient interviews with a 7-item questionnaire. Sub-millimeter targeting accuracy (0.71±0.31 mm) was recorded for frameless IGRS by a novel hidden-target phantom method. With a follow-up of 26 months, significant pain relief was recorded in 43 (89%) patients, including 26 (54%) complete and 17 (35%) partial responses; with a significant reduction of 2.4±1.3 points ( p < 0.01) on the 5-point Barrow Neurological Institute pain scale. No significant pain relief difference ( p = 0.23) was detected between patients immobilized by RF and FM. Notable pin site problems were reported in 9 (26%) of 34 patients immobilized by RF. Frameless IGRS with FM immobilization is more patient friendly and can achieve as excellent treatment outcome as with RF immobilization for idiopathic TGN.

  2. After microvascular decompression to treat trigeminal neuralgia, both immediate pain relief and recurrence rates are higher in patients with arterial compression than with venous compression.

    Science.gov (United States)

    Shi, Lei; Gu, Xiaoyan; Sun, Guan; Guo, Jun; Lin, Xin; Zhang, Shuguang; Qian, Chunfa

    2017-07-04

    We explored differences in postoperative pain relief achieved through decompression of the trigeminal nerve compressed by arteries and veins. Clinical characteristics, intraoperative findings, and postoperative curative effects were analyzed in 72 patients with trigeminal neuralgia who were treated by microvascular decompression. The patients were divided into arterial and venous compression groups based on intraoperative findings. Surgical curative effects included immediate relief, delayed relief, obvious reduction, and invalid result. Among the 40 patients in the arterial compression group, 32 had immediate pain relief of pain (80.0%), 5 cases had delayed relief (12.5%), and 3 cases had an obvious reduction (7.5%). In the venous compression group, 12 patients had immediate relief of pain (37.5%), 13 cases had delayed relief (40.6%), and 7 cases had an obvious reduction (21.9%). During 2-year follow-up period, 6 patients in the arterial compression group experienced recurrence of trigeminal neuralgia, but there were no recurrences in the venous compression group. Simple artery compression was followed by early relief of trigeminal neuralgia more often than simple venous compression. However, the trigeminal neuralgia recurrence rate was higher in the artery compression group than in the venous compression group.

  3. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.

    Science.gov (United States)

    Lukács, M; Warfvinge, K; Kruse, L S; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2016-12-01

    Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.

  4. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    Science.gov (United States)

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  5. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and

  6. Immunogenicity of an Intranasally Administered Modified Live Canine Parvovirus Type 2b Vaccine in Pups with Maternally Derived Antibodies

    Science.gov (United States)

    Martella, Vito; Cavalli, Alessandra; Decaro, Nicola; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Bozzo, Giancarlo; Tarsitano, Elvira; Buonavoglia, Canio

    2005-01-01

    The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of ≤80 and in 51.6% of pups with titers between 160 and 320. PMID:16210491

  7. Effect of intranasal mometasone furoate administered in children with coexisting allergic rhinitis and asthma towards asthma attacks and lung function

    Directory of Open Access Journals (Sweden)

    Ellen P. Gandaputra

    2009-12-01

    during the study. There was >50% improvement in allergic rhinitis symptoms after 4 weeks of treatment (P50% after 8 weeks of treatment (P50% of asthma symptoms, however it is not followed with significant improvement in lung function. No side effects are reported during 8 weeks use of intranasal mometasone furoate.

  8. Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

    Science.gov (United States)

    Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

    2006-08-01

    Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

  9. Enhanced Brain Delivery of 2-(Phosphonomethyl)pentanedioic Acid Following Intranasal Administration of Its gamma-Substituted Ester Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Nedelcovych, M.; Dash, R. P.; Tenora, Lukáš; Zimmermann, S. C.; Gadiano, A. J.; Garrett, C.; Alt, J.; Hollinger, K. R.; Pommier, E.; Jančařík, Andrej; Rojas, C.; Thomas, A. G.; Wu, Y.; Wozniak, K.; Majer, Pavel; Slusher, B. S.; Rais, R.

    2017-01-01

    Roč. 14, č. 10 (2017), s. 3248-3257 ISSN 1543-8384 Institutional support: RVO:61388963 Keywords : 2-PMPA * glutamate carboxypeptidase II * neurological disease * intranasal * pharmacokinetics * prodrugs Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 4.440, year: 2016

  10. AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

    Science.gov (United States)

    Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.

    2014-01-01

    This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  11. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

    Science.gov (United States)

    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  12. Immunogenicity of an Intranasally Administered Modified Live Canine Parvovirus Type 2b Vaccine in Pups with Maternally Derived Antibodies

    OpenAIRE

    Martella, Vito; Cavalli, Alessandra; Decaro, Nicola; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Bozzo, Giancarlo; Tarsitano, Elvira; Buonavoglia, Canio

    2005-01-01

    The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of ≤80 and in 51.6% of pups with titers between 160 and 320.

  13. Immunogenicity of an intranasally administered modified live canine parvovirus type 2b vaccine in pups with maternally derived antibodies.

    Science.gov (United States)

    Martella, Vito; Cavalli, Alessandra; Decaro, Nicola; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Bozzo, Giancarlo; Tarsitano, Elvira; Buonavoglia, Canio

    2005-10-01

    The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of < or = 80 and in 51.6% of pups with titers between 160 and 320.

  14. Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

    Science.gov (United States)

    Zhang, Shu; Huang, Shengshi; Lu, Lu; Song, Xinlei; Li, Pingli; Wang, Fengshan

    2018-01-01

    The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration. By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)- O -(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride ( O -HTCC) nanoparticles were prepared by interacting CS with O -HTCC, and the adjuvancy of the nanoparticles was investigated. The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/ O -HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/ O -HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/ O -HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/ O -HTCC evoked a significantly higher level of Ova-specific antibodies. Therefore, these results suggest that CS/ O -HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

  15. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

    Directory of Open Access Journals (Sweden)

    Sharareh Eskandari

    2011-02-01

    Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic c