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Sample records for trigeminovascular nociceptive transmission

  1. Comparative effects of traditional Chinese and Western migraine medicines in an animal model of nociceptive trigeminovascular activation.

    Science.gov (United States)

    Zhao, Yonglie; Martins-Oliveira, Margarida; Akerman, Simon; Goadsby, Peter J

    2017-01-01

    Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.

  2. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

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    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

    2014-01-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  3. Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety.

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    Rodrigo Noseda

    Full Text Available Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective and cognitive functions. Our overall goal is to define an anatomical framework for conceptualizing how a 'decision' is made on whether a trigeminovascular thalamic neuron fires, for how long, and at what frequency. To begin answering this question, we determine which neuropeptides/neurotransmitters are in a position to modulate thalamic trigeminovascular neurons. Using a combination of in-vivo single-unit recording, juxtacellular labeling with tetramethylrhodamine dextran (TMR and in-vitro immunohistochemistry, we found that thalamic trigeminovascular neurons were surrounded by high density of axons containing biomarkers of glutamate, GABA, dopamine and serotonin; moderate density of axons containing noradrenaline and histamine; low density of axons containing orexin and melanin concentrating hormone (MCH; but not axons containing CGRP, serotonin 1D receptor, oxytocin or vasopressin. In the context of migraine, the findings suggest that the transmission of headache-related nociceptive signals from the thalamus to the cortex may be modulated by opposing forces (i.e., facilitatory, inhibitory that are governed by continuous adjustments needed to keep physiological, behavioral, cognitive and emotional homeostasis.

  4. Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

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    Sessle, B J

    2000-01-01

    This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.

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

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    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

  6. Identifying brain nociceptive information transmission in patients with chronic somatic pain

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    Don A. Davis

    2016-10-01

    Conclusion:. Collectively, the results suggest that, across 2 types of chronic pain, nociceptive-specific information is relayed through the spinothalamic pathway to the lateral thalamus, potentiated by pronociceptive descending modulation, and interrupting cortical cognitive processes.

  7. The big CGRP flood - sources, sinks and signalling sites in the trigeminovascular system.

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    Messlinger, Karl

    2018-03-12

    Calcitonin gene-related peptide (CGRP) has long been a focus of migraine research, since it turned out that inhibition of CGRP or CGRP receptors by antagonists or monoclonal IgG antibodies was therapeutic in frequent and chronic migraine. This contribution deals with the questions, from which sites CGRP is released, where it is drained and where it acts to cause its headache proliferating effects in the trigeminovascular system. The available literature suggests that the bulk of CGRP is released from trigeminal afferents both in meningeal tissues and at the first synapse in the spinal trigeminal nucleus. CGRP may be drained off into three different compartments, the venous blood plasma, the cerebrospinal fluid and possibly the glymphatic system. CGRP receptors in peripheral tissues are located on arterial vessel walls, mononuclear immune cells and possibly Schwann cells; within the trigeminal ganglion they are located on neurons and glial cells; in the spinal trigeminal nucleus they can be found on central terminals of trigeminal afferents. All these structures are potential signalling sites for CGRP, where CGRP mediates arterial vasodilatation but not direct activation of trigeminal afferents. In the spinal trigeminal nucleus a facilitating effect on synaptic transmission seems likely. In the trigeminal ganglion CGRP is thought to initiate long-term changes including cross-signalling between neurons and glial cells based on gene expression. In this way, CGRP may upregulate the production of receptor proteins and pro-nociceptive molecules. CGRP and other big molecules cannot easily pass the blood-brain barrier. These molecules may act in the trigeminal ganglion to influence the production of pronociceptive substances and receptors, which are transported along the central terminals into the spinal trigeminal nucleus. In this way peripherally acting therapeutics can have a central antinociceptive effect.

  8. Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

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    Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

    2004-02-01

    There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

  9. Nociceptive transmission and modulation via P2X receptors in central pain syndrome.

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    Kuan, Yung-Hui; Shyu, Bai-Chuang

    2016-05-26

    Painful sensations are some of the most frequent complaints of patients who are admitted to local medical clinics. Persistent pain varies according to its causes, often resulting from local tissue damage or inflammation. Central somatosensory pathway lesions that are not adequately relieved can consequently cause central pain syndrome or central neuropathic pain. Research on the molecular mechanisms that underlie this pathogenesis is important for treating such pain. To date, evidence suggests the involvement of ion channels, including adenosine triphosphate (ATP)-gated cation channel P2X receptors, in central nervous system pain transmission and persistent modulation upon and following the occurrence of neuropathic pain. Several P2X receptor subtypes, including P2X2, P2X3, P2X4, and P2X7, have been shown to play diverse roles in the pathogenesis of central pain including the mediation of fast transmission in the peripheral nervous system and modulation of neuronal activity in the central nervous system. This review article highlights the role of the P2X family of ATP receptors in the pathogenesis of central neuropathic pain and pain transmission. We discuss basic research that may be translated to clinical application, suggesting that P2X receptors may be treatment targets for central pain syndrome.

  10. Direct Effect of Remifentanil and Glycine Contained in Ultiva® on Nociceptive Transmission in the Spinal Cord: In Vivo and Slice Patch Clamp Analyses.

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    Makoto Sumie

    Full Text Available Ultiva® is commonly administered intravenously for analgesia during general anaesthesia and its main constituent remifentanil is an ultra-short-acting μ-opioid receptor agonist. Ultiva® is not approved for epidural or intrathecal use in clinical practice. Previous studies have reported that Ultiva® provokes opioid-induced hyperalgesia by interacting with spinal dorsal horn neurons. Ultiva® contains glycine, an inhibitory neurotransmitter but also an N-methyl-D-aspartate receptor co-activator. The presence of glycine in the formulation of Ultiva® potentially complicates its effects. We examined how Ultiva® directly affects nociceptive transmission in the spinal cord.We made patch-clamp recordings from substantia gelatinosa (SG neurons in the adult rat spinal dorsal horn in vivo and in spinal cord slices. We perfused Ultiva® onto the SG neurons and analysed its effects on the membrane potentials and synaptic responses activated by noxious mechanical stimuli.Bath application of Ultiva® hyperpolarized membrane potentials under current-clamp conditions and produced an outward current under voltage-clamp conditions. A barrage of excitatory postsynaptic currents (EPSCs evoked by the stimuli was suppressed by Ultiva®. Miniature EPSCs (mEPSCs were depressed in frequency but not amplitude. Ultiva®-induced outward currents and suppression of mEPSCs were not inhibited by the μ-opioid receptor antagonist naloxone, but were inhibited by the glycine receptor antagonist strychnine. The Ultiva®-induced currents demonstrated a specific equilibrium potential similar to glycine.We found that intrathecal administration of Ultiva® to SG neurons hyperpolarized membrane potentials and depressed presynaptic glutamate release predominantly through the activation of glycine receptors. No Ultiva®-induced excitatory effects were observed in SG neurons. Our results suggest different analgesic mechanisms of Ultiva® between intrathecal and intravenous

  11. Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants.

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    Phillip Edward Kunkler

    Full Text Available Headache is the most common symptom associated with air pollution, but little is understood about the underlying mechanism. Nasal administration of environmental irritants activates the trigeminovascular system by a TRPA1-dependent process. This report addresses questions about the anatomical pathway involved and the function of TRP channels in this pathway. TRPV1 and TRPA1 are frequently co-localized and interact to modulate function in sensory neurons. We demonstrate here that resiniferatoxin ablation of TRPV1 expressing neurons significantly reduces meningeal blood flow responses to nasal administration of both TRPV1 and TRPA1 agonists. Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia. Sensory neurons of the trigeminal ganglia innervate the nasal epithelium and the meninges, but the mechanism and anatomical route by which nasal administration evokes meningeal vasodilatation is unclear. Double retrograde labeling from the nose and meninges reveals no co-localization of fluorescent label, however nasal and meningeal labeled cells are located in close proximity to each other within the trigeminal ganglion. Our data demonstrate that TRPV1 expressing neurons are important for TRPA1 responses in the nasal-meningeal pathway. Our data also suggest that the nasal-meningeal pathway is not primarily by axon reflex, but may instead result from intraganglionic transmission.

  12. Synaptic Plasticity and Nociception

    Institute of Scientific and Technical Information of China (English)

    ChenJianguo

    2004-01-01

    Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.

  13. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

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    Mamoru Takeda

    2016-10-01

    Full Text Available Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  14. PDE9A, PDE10A, and PDE11A expression in rat trigeminovascular pain signalling system

    DEFF Research Database (Denmark)

    Kruse, Lars S; Møller, Morten; Tibaek, Maiken

    2009-01-01

    as neocortex and cerebellar cortex. Real-time PCR and Western blotting showed that PDE9A, PDE10A and PDE11A are expressed in components of the rat trigeminovascular pain signalling system including middle cerebral artery, basilar artery, meninges, trigeminal ganglion and spinal trigeminal nucleus. Aorta...... and mesenteric artery as well as cerebral neocortex and cerebellar cortex also showed expression of PDE9A, PDE10A and PDE11A. Immunohistochemistry revealed that PDE9A, PDE10A and PDE11A are localised in the cytosol of nerve cell bodies of the trigeminal ganglion. We here present, for the first time...

  15. Predictive validity of endpoints used in electrophysiological modelling of migraine in the trigeminovascular system.

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    Farkas, Bence; Kardos, Péter; Orosz, Szabolcs; Tarnawa, István; Csekő, Csongor; Lévay, György; Farkas, Sándor; Lendvai, Balázs; Kovács, Péter

    2015-11-02

    The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons.

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    Weissman-Fogel, Irit; Sprecher, Elliot; Granovsky, Yelena; Yarnitsky, David

    2003-08-01

    Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight

  17. Shielding cognition from nociception with working memory.

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    Legrain, Valéry; Crombez, Geert; Plaghki, Léon; Mouraux, André

    2013-01-01

    Because pain often signals the occurrence of potential tissue damage, nociceptive stimuli have the capacity to capture attention and interfere with ongoing cognitive activities. Working memory is known to guide the orientation of attention by maintaining goal priorities active during the achievement of a task. This study investigated whether the cortical processing of nociceptive stimuli and their ability to capture attention are under the control of working memory. Event-related brain potentials (ERPs) were recorded while participants performed primary tasks on visual targets that required or did not require rehearsal in working memory (1-back vs 0-back conditions). The visual targets were shortly preceded by task-irrelevant tactile stimuli. Occasionally, in order to distract the participants, the tactile stimuli were replaced by novel nociceptive stimuli. In the 0-back conditions, task performance was disrupted by the occurrence of the nociceptive distracters, as reflected by the increased reaction times in trials with novel nociceptive distracters as compared to trials with standard tactile distracters. In the 1-back conditions, such a difference disappeared suggesting that attentional capture and task disruption induced by nociceptive distracters were suppressed by working memory, regardless of task demands. Most importantly, in the conditions involving working memory, the magnitude of nociceptive ERPs, including ERP components at early latency, were significantly reduced. This indicates that working memory is able to modulate the cortical processing of nociceptive input already at its earliest stages, and could explain why working memory reduces consequently ability of nociceptive stimuli to capture attention and disrupt performance of the primary task. It is concluded that protecting cognitive processing against pain interference is best guaranteed by keeping out of working memory pain-related information. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Calcitonin gene-related peptide modulates heat nociception in the human brain - An fMRI study in healthy volunteers

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    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B.W.

    2016-01-01

    Background: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...... cortex. Sumatriptan injection reversed these changes. Conclusion: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli....

  19. Expression of nociceptive ligands in canine osteosarcoma.

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    Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  20. Role of NHE1 in Nociception

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    Jorge Elías Torres-López

    2013-01-01

    Full Text Available Intracellular pH is a fundamental parameter to cell function that requires tight homeostasis. In the absence of any regulation, excessive acidification of the cytosol would have the tendency to produce cellular damage. Mammalian Na+/H+ exchangers (NHEs are electroneutral Na+-dependent proteins that exchange extracellular Na+ for intracellular H+. To date, there are 9 identified NHE isoforms where NHE1 is the most ubiquitous member, known as the housekeeping exchanger. NHE1 seems to have a protective role in the ischemia-reperfusion injury and other inflammatory diseases. In nociception, NHE1 is found in neurons along nociceptive pathways, and its pharmacological inhibition increases nociceptive behavior in acute pain models at peripheral and central levels. Electrophysiological studies also show that NHE modulates electrical activity of primary nociceptive terminals. However, its role in neuropathic pain still remains controversial. In humans, NHE1 may be responsible for inflammatory bowel diseases since its expression is reduced in Crohn’s disease and ulcerative colitis. The purpose of this work is to provide a review of the evidence about participation of NHE1 in the nociceptive processing.

  1. Slack KNa Channels Influence Dorsal Horn Synapses and Nociceptive Behavior.

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    Evely, Katherine M; Pryce, Kerri D; Bausch, Anne E; Lukowski, Robert; Ruth, Peter; Haj-Dahmane, Samir; Bhattacharjee, Arin

    2017-01-01

    The sodium-activated potassium channel Slack (Kcnt1, Slo2.2) is highly expressed in dorsal root ganglion neurons where it regulates neuronal firing. Several studies have implicated the Slack channel in pain processing, but the precise mechanism or the levels within the sensory pathway where channels are involved remain unclear. Here, we furthered the behavioral characterization of Slack channel knockout mice and for the first time examined the role of Slack channels in the superficial, pain-processing lamina of the dorsal horn. We performed whole-cell recordings from spinal cord slices to examine the intrinsic and synaptic properties of putative inhibitory and excitatory lamina II interneurons. Slack channel deletion altered intrinsic properties and synaptic drive to favor an overall enhanced excitatory tone. We measured the amplitudes and paired pulse ratio of paired excitatory post-synaptic currents at primary afferent synapses evoked by electrical stimulation of the dorsal root entry zone. We found a substantial decrease in the paired pulse ratio at synapses in Slack deleted neurons compared to wildtype, indicating increased presynaptic release from primary afferents. Corroborating these data, plantar test showed Slack knockout mice have an enhanced nociceptive responsiveness to localized thermal stimuli compared to wildtype mice. Our findings suggest that Slack channels regulate synaptic transmission within the spinal cord dorsal horn and by doing so establishes the threshold for thermal nociception.

  2. Nociceptor-Enriched Genes Required for Normal Thermal Nociception

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    Ken Honjo

    2016-07-01

    Full Text Available Here, we describe a targeted reverse genetic screen for thermal nociception genes in Drosophila larvae. Using laser capture microdissection and microarray analyses of nociceptive and non-nociceptive neurons, we identified 275 nociceptor-enriched genes. We then tested the function of the enriched genes with nociceptor-specific RNAi and thermal nociception assays. Tissue-specific RNAi targeted against 14 genes caused insensitive thermal nociception while targeting of 22 genes caused hypersensitive thermal nociception. Previously uncategorized genes were named for heat resistance (i.e., boilerman, fire dancer, oven mitt, trivet, thawb, and bunker gear or heat sensitivity (firelighter, black match, eucalyptus, primacord, jet fuel, detonator, gasoline, smoke alarm, and jetboil. Insensitive nociception phenotypes were often associated with severely reduced branching of nociceptor neurites and hyperbranched dendrites were seen in two of the hypersensitive cases. Many genes that we identified are conserved in mammals.

  3. Nociceptive Effects of Locally Treated Metoprolol

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    Nursima Cukadar

    2015-06-01

    Results: Metoprolol, an antagonist, significantly decreased the thermal latency and mechanical thresholds with dose and time dependent manner. However, dobutamine, an agonist, enhanced the latency and thresholds dose and time dependent. Conclusions: This results suggest that in contrast to dobutamine, locally treated metoprolol may cause hyperalgesic and allodynic actions. In addition, our results can demonstrate that peripheral beta-adrenergic receptors can play important roles in nociceptive process. [Cukurova Med J 2015; 40(2.000: 258-266

  4. Cellular mechanisms of nociception in the frog

    Czech Academy of Sciences Publication Activity Database

    Kuffler, D. P.; Lyfenko, Alla; Vyklický st., Ladislav; Vlachová, Viktorie

    2002-01-01

    Roč. 88, č. 4 (2002), s. 1843-1850 ISSN 0022-3077 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Grant - others:NATO(XX) Grant 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : cellular mechanisms of nociception * frog Subject RIV: FH - Neurology Impact factor: 3.743, year: 2002

  5. CGRPα within the Trpv1-Cre population contributes to visceral nociception.

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    Spencer, Nick J; Magnúsdóttir, Elín I; Jakobsson, Jon E T; Kestell, Garreth; Chen, Bao Nan; Morris, David; Brookes, Simon J; Lagerström, Malin C

    2018-02-01

    The role of calcitonin gene-related peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPα is highly expressed in sensory neurons of dorsal root ganglia and particularly in neurons that also express the transient receptor potential cation channel subfamily V member 1 (Trpv1). Therefore, we investigated changes in visceral and somatic nociception following deletion of CGRPα from the Trpv1-Cre population using the Cre/lox system. In control mice, acetic acid injection (0.6%, ip) caused significant immobility (time stationary), an established indicator of visceral pain. In CGRPα-mCherry lx/lx ;Trpv1-Cre mice, the duration of immobility was significantly less than controls, and the distance CGRPα-mCherry lx/lx ;Trpv1-Cre mice traveled over 20 min following acetic acid was significantly greater than controls. However, following acetic acid injection, there was no difference between genotypes in the writhing reflex, number of abdominal licks, or forepaw wipes of the cheek. CGRPα-mCherry lx/lx ;Trpv1-Cre mice developed more pronounced inflammation-induced heat hypersensitivity above baseline values compared with controls. However, analyses of noxious acute heat or cold transmission revealed no difference between genotypes. Also, odor avoidance test, odor preference test, and buried food test for olfaction revealed no differences between genotypes. Our findings suggest that CGRPα-mediated transmission within the Trpv1-Cre population plays a significant role in visceral nociceptive pathways underlying voluntary movement. Monitoring changes in movement over time is a sensitive parameter to identify differences in visceral nociception, compared with writhing reflexes, abdominal licks, or forepaw wipes of the cheek that were unaffected by deletion of CGRPα- from Trpv1-Cre population and likely utilize different mechanisms. NEW & NOTEWORTHY The neuropeptide calcitonin gene-related peptide (CGRP) is highly colocalized with transient receptor

  6. Factors affecting mechanical (nociceptive) thresholds in piglets.

    Science.gov (United States)

    Janczak, Andrew M; Ranheim, Birgit; Fosse, Torunn K; Hild, Sophie; Nordgreen, Janicke; Moe, Randi O; Zanella, Adroaldo J

    2012-11-01

    To evaluate the stability and repeatability of measures of mechanical (nociceptive) thresholds in piglets and to examine potentially confounding factors when using a hand held algometer. Descriptive, prospective cohort. Forty-four piglets from four litters, weighing 4.6 ± 1.0 kg (mean ± SD) at 2 weeks of age. Mechanical thresholds were measured twice on each of 2 days during the first and second week of life. Data were analyzed using a repeated measures design to test the effects of behavior prior to testing, sex, week, day within week, and repetition within day. The effect of body weight and the interaction between piglet weight and behaviour were also tested. Piglet was entered into the model as a random effect as an additional test of repeatability. The effect of repeated testing was used to test the stability of measures. Pearson correlations between repeated measures were used to test the repeatability of measures. Variance component analysis was used to describe the variability in the data. Variance component analysis indicated that piglet explained only 17% of the variance in the data. All variables in the model (behaviour prior to testing, sex, week, day within week, repetition within day, body weight, the interaction between body weight and behaviour, piglet identity) except sex had a significant effect (p testing and measures changed with repeated testing and increased with increasing piglet weight, indicating that time (age) and animal body weight should be taken into account when measuring mechanical (nociceptive) thresholds in piglets. Mechanical (nociceptive) thresholds can be used both for testing the efficacy of anaesthetics and analgesics, and for assessing hyperalgesia in chronic pain states in research and clinical settings. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  7. Controlling attention to nociceptive stimuli with working memory.

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    Valéry Legrain

    Full Text Available BACKGROUND: Because pain often signals the occurrence of potential tissue damage, a nociceptive stimulus has the capacity to involuntarily capture attention and take priority over other sensory inputs. Whether distraction by nociception actually occurs may depend upon the cognitive characteristics of the ongoing activities. The present study tested the role of working memory in controlling the attentional capture by nociception. METHODOLOGY AND PRINCIPAL FINDINGS: Participants performed visual discrimination and matching tasks in which visual targets were shortly preceded by a tactile distracter. The two tasks were chosen because of the different effects the involvement of working memory produces on performance, in order to dissociate the specific role of working memory in the control of attention from the effect of general resource demands. Occasionally (i.e. 17% of the trials, tactile distracters were replaced by a novel nociceptive stimulus in order to distract participants from the visual tasks. Indeed, in the control conditions (no working memory, reaction times to visual targets were increased when the target was preceded by a novel nociceptive distracter as compared to the target preceded by a frequent tactile distracter, suggesting attentional capture by the novel nociceptive stimulus. However, when the task required an active rehearsal of the visual target in working memory, the novel nociceptive stimulus no longer induced a lengthening of reaction times to visual targets, indicating a reduction of the distraction produced by the novel nociceptive stimulus. This effect was independent of the overall task demands. CONCLUSION AND SIGNIFICANCE: Loading working memory with pain-unrelated information may reduce the ability of nociceptive input to involuntarily capture attention, and shields cognitive processing from nociceptive distraction. An efficient control of attention over pain is best guaranteed by the ability to maintain active goal

  8. CORTICAL RESPONSES TO SALIENT NOCICEPTIVE AND NOT NOCICEPTIVE STIMULI IN VEGETATIVE AND MINIMAL CONSCIOUS STATE

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    MARINA eDE TOMMASO

    2015-01-01

    Full Text Available Aims Questions regarding perception of pain in non-communicating patients and the management of pain continue to raise controversy both at a clinical and ethical level. The aim of this study was to examine the cortical response to salient multimodal visual, acoustic, somatosensory electric non nociceptive and nociceptive laser stimuli and their correlation with the clinical evaluation.Methods: Five Vegetative State (VS, 4 Minimally Conscious State (MCS patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, while delivering auditory, visual, non-noxious electrical and noxious laser stimulation, which were randomly presented every 10 sec. Laser, somatosensory, auditory and visual evoked responses were identified as a negative-positive (N2-P2 vertex complex in the 500 msec post-stimulus time. We used Nociception Coma Scale-Revised (NCS-R and Coma Recovery Scale (CRS-R for clinical evaluation of pain perception and consciousness impairment.Results: The laser evoked potentials (LEPs were recognizable in all cases. Only one MCS patient showed a reliable cortical response to all the employed stimulus modalities. One VS patient did not present cortical responses to any other stimulus modality. In the remaining participants, auditory, visual and electrical related potentials were inconstantly present. Significant N2 and P2 latency prolongation occurred in both VS and MCS patients. The presence of a reliable cortical response to auditory, visual and electric stimuli was able to correctly classify VS and MCS patients with 90% accuracy. Laser P2 and N2 amplitudes were not correlated with the CRS-R and NCS-R scores, while auditory and electric related potentials amplitude were associated with the motor response to pain and consciousness recovery. Discussion: pain arousal may be a primary function also in vegetative state patients while the relevance of other stimulus modalities may indicate the

  9. Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

    Science.gov (United States)

    Kadow, Brian T; Lyon, Timothy D; Zhang, Zhaocun; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-07-01

    This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition. Copyright © 2016 the American Physiological Society.

  10. DNA Methylation Modulates Nociceptive Sensitization after Incision.

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    Yuan Sun

    Full Text Available DNA methylation is a key epigenetic mechanism controlling DNA accessibility and gene expression. Blockade of DNA methylation can significantly affect pain behaviors implicated in neuropathic and inflammatory pain. However, the role of DNA methylation with regard to postoperative pain has not yet been explored. In this study we sought to investigate the role of DNA methylation in modulating incisional pain and identify possible targets under DNA methylation and contributing to incisional pain. DNA methyltranferase (DNMT inhibitor 5-Aza-2'-deoxycytidine significantly reduced incision-induced mechanical allodynia and thermal sensitivity. Aza-2'-deoxycytidine also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. Global DNA methylation and DNMT3b expression were increased in skin after incision, but none of DNMT1, DNMT3a or DNMT3b was altered in spinal cord or DRG. The expression of proopiomelanocortin Pomc encoding β-endorphin and Oprm1 encoding the mu-opioid receptor were upregulated peripherally after incision; moreover, Oprm1 expression was further increased under DNMT inhibitor treatment. Finally, local peripheral injection of the opioid receptor antagonist naloxone significantly exacerbated incision-induced mechanical hypersensitivity. These results suggest that DNA methylation is functionally relevant to incisional nociceptive sensitization, and that mu-opioid receptor signaling might be one methylation regulated pathway controlling sensitization after incision.

  11. Cortical responses to salient nociceptive and not nociceptive stimuli in vegetative and minimal conscious state

    Science.gov (United States)

    de Tommaso, Marina; Navarro, Jorge; Lanzillotti, Crocifissa; Ricci, Katia; Buonocunto, Francesca; Livrea, Paolo; Lancioni, Giulio E.

    2015-01-01

    Aims: Questions regarding perception of pain in non-communicating patients and the management of pain continue to raise controversy both at a clinical and ethical level. The aim of this study was to examine the cortical response to salient visual, acoustic, somatosensory electric non-nociceptive and nociceptive laser stimuli and their correlation with the clinical evaluation. Methods: Five Vegetative State (VS), 4 Minimally Conscious State (MCS) patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, while delivering auditory, visual, non-noxious electrical and noxious laser stimulation, which were randomly presented every 10 s. Laser, somatosensory, auditory and visual evoked responses were identified as a negative-positive (N2-P2) vertex complex in the 500 ms post-stimulus time. We used Nociception Coma Scale-Revised (NCS-R) and Coma Recovery Scale (CRS-R) for clinical evaluation of pain perception and consciousness impairment. Results: The laser evoked potentials (LEPs) were recognizable in all cases. Only one MCS patient showed a reliable cortical response to all the employed stimulus modalities. One VS patient did not present cortical responses to any other stimulus modality. In the remaining participants, auditory, visual and electrical related potentials were inconstantly present. Significant N2 and P2 latency prolongation occurred in both VS and MCS patients. The presence of a reliable cortical response to auditory, visual and electric stimuli was able to correctly classify VS and MCS patients with 90% accuracy. Laser P2 and N2 amplitudes were not correlated with the CRS-R and NCS-R scores, while auditory and electric related potentials amplitude were associated with the motor response to pain and consciousness recovery. Discussion: pain arousal may be a primary function also in vegetative state patients while the relevance of other stimulus modalities may indicate the degree of cognitive and motor

  12. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Buscher, H.C.J.L.; Goor, H. van; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND AND OBJECTIVES: : Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain

  13. Intraplantar injection of tetrahydrobiopterin induces nociception in mice

    DEFF Research Database (Denmark)

    Nasser, Arafat; Ali, Sawsan; Wilsbech, Signe

    2015-01-01

    was tested. Morphine served as a positive control. Intraplantar pre-injection of morphine dose-dependently inhibited BH4-induced nociception, while none of the other compounds showed any statistical significant antinociception. These results suggest that BH4 exhibits nociceptive properties at peripheral......Tetrahydrobiopterin (BH4) is implicated in the development and maintenance of chronic pain. After injury/inflammation, the biosynthesis of BH4 is markedly increased in sensory neurons, and the pharmacological and genetic inhibition of BH4 shows analgesic effects in pre-clinical animal pain models...

  14. Effect of a nitric oxide donor (glyceryl trinitrate) on nociceptive thresholds in man

    DEFF Research Database (Denmark)

    Thomsen, L L; Brennum, J; Iversen, Helle Klingenberg

    1996-01-01

    Several animal studies suggest that nitric oxide (NO) plays a role in central and peripheral modulation of nociception. Glyceryl trinitrate (GTN) exerts its physiological actions via donation of NO. The purpose of the present study was to examine the effect of this NO donor on nociceptive...... central facilitation of nociception by NO. However, we regard convergence of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO as a more likely explanation of our findings....

  15. A study of the reliability of the Nociception Coma Scale.

    Science.gov (United States)

    Riganello, F; Cortese, M D; Arcuri, F; Candelieri, A; Guglielmino, F; Dolce, G; Sannita, W G; Schnakers, C

    2015-04-01

    In this study, we investigated the reliability of the Nociception Coma Scale which has recently been developed to assess nociception in non-communicative, severely brain-injured patients. Prospective cross-sequential study. Semi-intensive care unit and long-term brain injury care. Forty-four patients diagnosed as being in a vegetative state (n=26) or in a minimally conscious state (n=18). Patients were assessed by two experts (rater A and rater B) on two consecutive weeks to measure inter-rater agreement and test-retest reliability. Total scores and subscores of the Nociception Coma Scale. We performed a total of 176 assessments. The inter-rater agreement was moderate for the total scores (k = 0.57) and fair to substantial for the subscores (0.33 ≤ k ≤ 0.62) on week 2. The test-retest reliability was substantial for the total scores (k = 0.66) and moderate to almost perfect for the subscores (0.53 ≤ k ≤ 0.96) for rater A. The inter-rater agreement was weaker on week 1, whereas the test-retest reliability was lower for the least experienced rater (rater B). This study provides further evidence of the psychometric qualities of the Nociception Coma Scale. Future studies should assess the impact of practical experience and background on administration and scoring of the scale. © The Author(s) 2014.

  16. Nociceptive flexion reflexes during analgesic neurostimulation in man.

    Science.gov (United States)

    García-Larrea, L; Sindou, M; Mauguière, F

    1989-11-01

    Nociceptive flexion reflexes of the lower limbs (RIII responses) have been studied in 21 patients undergoing either epidural (DCS, n = 16) or transcutaneous (TENS, n = 5) analgesic neurostimulation (AN) for chronic intractable pain. Flexion reflex RIII was depressed or suppressed by AN in 11 patients (52.4%), while no modification was observed in 9 cases and a paradoxical increase during AN was evidenced in 1 case. In all but 2 patients, RIII changes were rapidly reversible after AN interruption. RIII depression was significantly associated with subjective pain relief, as assessed by conventional self-rating; moreover, in 2 patients it was possible to ameliorate the pain-suppressing effects of AN by selecting those stimulation parameters (intensity and frequency) that maximally depressed nociceptive reflex RIII. We recorded 2 cases of RIII attenuation after contralateral neurostimulation. AN appeared to affect nociceptive reflexes rather selectively, with no or very little effect on other cutaneous, non-nociceptive responses. Recording of RIII reflexes is relatively simple to implement as a routine paraclinical procedure. It facilitates the objective assessment of AN efficacy and may help to choose the most appropriate parameters of neurostimulation. In addition, RIII behavior in patients could be relevant to the understanding of some of the mechanisms involved in AN-induced pain relief.

  17. Citral reduces nociceptive and inflammatory response in rodents

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    Lucindo J. Quintans-Júnior

    2011-04-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  18. Nociception at the diabetic foot, an uncharted territory

    Science.gov (United States)

    Chantelau, Ernst A

    2015-01-01

    The diabetic foot is characterised by painless foot ulceration and/or arthropathy; it is a typical complication of painless diabetic neuropathy. Neuropathy depletes the foot skin of intraepidermal nerve fibre endings of the afferent A-delta and C-fibres, which are mostly nociceptors and excitable by noxious stimuli only. However, some of them are cold or warm receptors whose functions in diabetic neuropathy have frequently been reported. Hence, it is well established by quantitative sensory testing that thermal detection thresholds at the foot skin increase during the course of painless diabetic neuropathy. Pain perception (nociception), by contrast, has rarely been studied. Recent pilot studies of pinprick pain at plantar digital skinfolds showed that the perception threshold was always above the upper limit of measurement of 512 mN (equivalent to 51.2 g) at the diabetic foot. However, deep pressure pain perception threshold at musculus abductor hallucis was beyond 1400 kPa (equivalent to 14 kg; limit of measurement) only in every fifth case. These discrepancies of pain perception between forefoot and hindfoot, and between skin and muscle, demand further study. Measuring nociception at the feet in diabetes opens promising clinical perspectives. A critical nociception threshold may be quantified (probably corresponding to a critical number of intraepidermal nerve fibre endings), beyond which the individual risk of a diabetic foot rises appreciably. Staging of diabetic neuropathy according to nociception thresholds at the feet is highly desirable as guidance to an individualised injury prevention strategy. PMID:25897350

  19. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  20. Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion.

    Science.gov (United States)

    Ogata, M; Noda, K; Akita, H; Ishibashi, H

    2015-03-19

    Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment during adulthood and the neonatal period exhibit akinetic motor activity and spontaneous motor hyperactivity during adolescence, respectively, indicating that the behavioral effects of dopamine depletion depend on the period of lesion development. Dopamine depletion during adulthood induces hyperalgesic response to mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal dopamine depletion on nociceptive response in adolescent rats are yet to be examined. The latter aspect was addressed in this study, and behavioral responses were examined using von-Frey, tail flick, and formalin tests. The formalin test revealed that rats with neonatal dopamine depletion exhibited a significant increase in nociceptive response during interphase (6-15min post formalin injection) and phase 2 (16-75min post formalin injection). This increase in nociceptive response to the formalin injection was not reversed by pretreatment with methamphetamine, which ameliorates motor hyperactivity observed in adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail flick tests failed to reveal significant differences in withdrawal thresholds between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal response to the formalin injection into the rat hind paw was also examined through immunohistochemical analysis of c-Fos protein. Significantly increased numbers of c-Fos-immunoreactive cells were observed in laminae I-II and V-VI of the ipsilateral spinal cord to the site of the formalin injection in rats with neonatal dopamine depletion compared with vehicle-treated rats. These results suggest that the dopaminergic neural system plays a crucial role in the development of a neural network for tonic pain, including the spinal neural circuit for nociceptive transmission, and that the mechanism underlying hyperalgesia to tonic pain is not always consistent with that of

  1. Impact of Behavioral Control on the Processing of Nociceptive Stimulation

    Science.gov (United States)

    Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

    2012-01-01

    How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

  2. p-Cymene reduces orofacial nociceptive response in mice

    Directory of Open Access Journals (Sweden)

    Michele F. Santana

    2011-12-01

    Full Text Available This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice were pretreated (i.p. with p-cymene (25, 50, 100 mg/kg, morphine (5 mg/kg, or vehicle (0.2% Tween 80+saline, and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min, and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p. was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg. Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001 the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg. Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

  3. Impact of behavioral control on the processing of nociceptive stimulation

    Directory of Open Access Journals (Sweden)

    James W Grau

    2012-08-01

    Full Text Available How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation, it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation. These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: Controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit. Uncontrollable stimulation also enhances mechanical reactivity (allodynia. We review evidence that training with controllable stimulation engages a BDNF-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin. A model is proposed that assumes nociceptive input is gated at an early stage, within the dorsal horn. his gate is sensitive to current environmental relations (between proprioceptive and nociceptive input, allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain.

  4. Interactions between superficial and deep dorsal horn spinal cord neurons in the processing of nociceptive information.

    Science.gov (United States)

    Petitjean, Hugues; Rodeau, Jean-Luc; Schlichter, Rémy

    2012-12-01

    In acute rat spinal cord slices, the application of capsaicin (5 μm, 90 s), an agonist of transient receptor potential vanilloid 1 receptors expressed by a subset of nociceptors that project to laminae I-II of the spinal cord dorsal horn, induced an increase in the frequency of spontaneous excitatory and spontaneous inhibitory postsynaptic currents in about half of the neurons in laminae II, III-IV and V. In the presence of tetrodotoxin, which blocks action potential generation and polysynaptic transmission, capsaicin increased the frequency of miniature excitatory postsynaptic currents in only 30% of lamina II neurons and had no effect on the frequency of miniature excitatory postsynaptic currents in laminae III-V or on the frequency of miniature inhibitory postsynaptic currents in laminae II-V. When the communication between lamina V and more superficial laminae was interrupted by performing a mechanical section between laminae IV and V, capsaicin induced an increase in spontaneous excitatory postsynaptic current frequency in laminae II-IV and an increase in spontaneous inhibitory postsynaptic current frequency in lamina II that were similar to those observed in intact slices. However, in laminae III-IV of transected slices, the increase in spontaneous inhibitory postsynaptic current frequency was virtually abolished. Our results indicate that nociceptive information conveyed by transient receptor potential vanilloid 1-expressing nociceptors is transmitted from lamina II to deeper laminae essentially by an excitatory pathway and that deep laminae exert a 'feedback' control over neurons in laminae III-IV by increasing inhibitory synaptic transmission in these laminae. Moreover, we provide evidence that laminae III-IV might play an important role in the processing of nociceptive information in the dorsal horn. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. The Role of PPK26 in Drosophila Larval Mechanical Nociception

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    Yanmeng Guo

    2014-11-01

    Full Text Available In Drosophila larvae, the class IV dendritic arborization (da neurons are polymodal nociceptors. Here, we show that ppk26 (CG8546 plays an important role in mechanical nociception in class IV da neurons. Our immunohistochemical and functional results demonstrate that ppk26 is specifically expressed in class IV da neurons. Larvae with mutant ppk26 showed severe behavioral defects in a mechanical nociception behavioral test but responded to noxious heat stimuli comparably to wild-type larvae. In addition, functional studies suggest that ppk26 and ppk (also called ppk1 function in the same pathway, whereas piezo functions in a parallel pathway. Consistent with these functional results, we found that PPK and PPK26 are interdependent on each other for their cell surface localization. Our work indicates that PPK26 and PPK might form heteromeric DEG/ENaC channels that are essential for mechanotransduction in class IV da neurons.

  6. Comparative biology of pain: What invertebrates can tell us about how nociception works.

    Science.gov (United States)

    Burrell, Brian D

    2017-04-01

    The inability to adequately treat chronic pain is a worldwide health care crisis. Pain has both an emotional and a sensory component, and this latter component, nociception, refers specifically to the detection of damaging or potentially damaging stimuli. Nociception represents a critical interaction between an animal and its environment and exhibits considerable evolutionary conservation across species. Using comparative approaches to understand the basic biology of nociception could promote the development of novel therapeutic strategies to treat pain, and studies of nociception in invertebrates can provide especially useful insights toward this goal. Both vertebrates and invertebrates exhibit segregated sensory pathways for nociceptive and nonnociceptive information, injury-induced sensitization to nociceptive and nonnociceptive stimuli, and even similar antinociceptive modulatory processes. In a number of invertebrate species, the central nervous system is understood in considerable detail, and it is often possible to record from and/or manipulate single identifiable neurons through either molecular genetic or physiological approaches. Invertebrates also provide an opportunity to study nociception in an ethologically relevant context that can provide novel insights into the nature of how injury-inducing stimuli produce persistent changes in behavior. Despite these advantages, invertebrates have been underutilized in nociception research. In this review, findings from invertebrate nociception studies are summarized, and proposals for how research using invertebrates can address questions about the fundamental mechanisms of nociception are presented. Copyright © 2017 the American Physiological Society.

  7. Citral reduces nociceptive and inflammatory response in rodents

    OpenAIRE

    Quintans-Júnior, Lucindo J.; Guimarães, Adriana G.; Santana, Marilia T. de; Araújo, Bruno E.S.; Moreira, Flávia V.; Bonjardim, Leonardo R.; Araújo, Adriano A. S.; Siqueira, Jullyana S.; Antoniolli, Ângelo R.; Botelho, Marco A.; Almeida, Jackson R. G. S.; Santos, Márcio R. V.

    2011-01-01

    Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT...

  8. (-)-α-Bisabolol reduces orofacial nociceptive behavior in rodents.

    Science.gov (United States)

    Melo, Luana Torres; Duailibe, Mariana Araújo Braz; Pessoa, Luciana Moura; da Costa, Flávio Nogueira; Vieira-Neto, Antonio Eufrásio; de Vasconcellos Abdon, Ana Paula; Campos, Adriana Rolim

    2017-02-01

    The purposes of this study were to evaluate the anti-nociceptive effect of oral and topical administration of (-)-α-bisabolol (BISA) in rodent models of formalin- or cinnamaldehyde-induced orofacial pain and to explore the inhibitory mechanisms involved. Orofacial pain was induced by injecting 1.5% formalin into the upper lip of mice (20 μL) or into the temporomandibular joint (TMJ) of rats (50 μL). In another experiment, orofacial pain was induced with cinnamaldehyde (13.2 μg/lip). Nociceptive behavior was proxied by time (s) spent rubbing the injected area and by the incidence of head flinching. BISA (100, 200, or 400 mg/kg p.o. or 50, 100, or 200 mg/mL topical) or vehicle was administered 60 min before pain induction. The two formulations (lotion and syrup) were compared with regard to efficacy. The effect of BISA remained after incorporation into the formulations, and nociceptive behavior decreased significantly in all tests. The high binding affinity observed for BISA and TRPA1 in the molecular docking study was supported by in vivo experiments in which HC-030031 (a TRPA1 receptor antagonist) attenuated pain in a manner qualitatively and quantitatively similar to that of BISA. Blockers of opioid receptors, NO synthesis, and K + ATP channels did not affect orofacial pain, nor inhibit the effect of BISA. In conclusion, BISA had a significant anti-nociceptive effect on orofacial pain. The effect may in part be due to TRPA1 antagonism. The fact that the effect of BISA remained after incorporation into oral and topical formulations suggests that the compound may be a useful adjuvant in the treatment of orofacial pain.

  9. Chronic intrathecal cannulation enhances nociceptive responses in rats

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    Almeida F.R.C.

    2000-01-01

    Full Text Available The influence of a chronically implanted spinal cannula on the nociceptive response induced by mechanical, chemical or thermal stimuli was evaluated. The hyperalgesia in response to mechanical stimulation induced by carrageenin or prostaglandin E2 (PGE2 was significantly increased in cannulated (Cn rats, compared with naive (Nv or sham-operated (Sh rats. Only Cn animals presented an enhanced nociceptive response in the first phase of the formalin test when low doses were used (0.3 and 1%. The withdrawal latency to thermal stimulation of a paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non-steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into the spinal cord via an implanted cannula or by direct puncture of the intrathecal space significantly blocked the intensity of the hyperalgesia induced by PGE2. Cannulated animals treated with indomethacin also showed a significant inhibition of second phase formalin-induced paw flinches. Histopathological analysis of the spinal cord showed an increased frequency of mononuclear inflammatory cells in the Cn groups. Thus, the presence of a chronically implanted cannula seems to cause nociceptive spinal sensitization to mechanical, chemical and thermal stimulation, which can be blocked by indomethacin, thus suggesting that it may result from the spinal release of prostaglandins due to an ongoing mild inflammation.

  10. D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats.

    Science.gov (United States)

    Ohtani, Norimasa; Masaki, Eiji

    2016-01-01

    Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats. Male Sprague-Dawley rats (250-300 g) were anesthetized with sevoflurane and an intrathecal (IT) catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole), or a D2-like receptor antagonist (sulpiride) was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision. Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect. A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold.

  11. D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

    Directory of Open Access Journals (Sweden)

    Ohtani N

    2016-10-01

    Full Text Available Norimasa Ohtani, Eiji Masaki Division of Dento-oral Anesthesiology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan Background: Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats.Methods: Male Sprague-Dawley rats (250–300 g were anesthetized with sevoflurane and an intrathecal (IT catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole, or a D2-like receptor antagonist (sulpiride was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision.Results: Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect.Conclusion: A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold. Keywords: postoperative pain, descending pathway

  12. Network dynamics in nociceptive pathways assessed by the neuronal avalanche model

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    Wu José

    2012-04-01

    Full Text Available Abstract Background Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the α value. We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment. Findings Neuronal activity was recorded with a 4 × 8 multichannel electrode array in the primary somatosensory cortex (S1 and anterior cingulate cortex (ACC. Under light anesthesia, peripheral pinch stimulation increased the slope of the α value in both the ACC and S1, whereas brush stimulation increased the α value only in the S1. The increase in α values was blocked in both regions under deep anesthesia. The increase in α values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in α values in the S1 induced by brush and pinch stimulation was not affected. Conclusions The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The α value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.

  13. Changes in thermal nociceptive responses in dairy cows following experimentally induced Esherichia coli mastitis

    DEFF Research Database (Denmark)

    Rasmussen, Ditte B.; Fogsgaard, Katrine; Røntved, Christine Maria

    2011-01-01

    Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS......) in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables....

  14. Neonatal morphine enhances nociception and decreases analgesia in young rats.

    Science.gov (United States)

    Zhang, Guo Hua; Sweitzer, Sarah M

    2008-03-14

    The recognition of the impact of neonatal pain experience on subsequent sensory processing has led to the increased advocacy for the use of opioids for pain relief in infants. However, following long-term opioid exposure in intensive care units more than 48% of infants exhibited behaviors indicative of opioid abstinence syndrome, a developmentally equivalent set of behaviors to opioid withdrawal as seen in adults. Little is known about the long-term influence of repeated neonatal morphine exposure on nociception and analgesia. To investigate this, we examined mechanical and thermal nociception on postnatal days 11, 13, 15, 19, 24, 29, 39 and 48 following subcutaneous administration of morphine (3 mg/kg) once daily on postnatal days 1-9. The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49. Both basal mechanical and thermal nociception in neonatal, morphine-exposed rats were significantly lower than those in saline-exposed, handled-control rats and naive rats until P29. A rightward-shift of cumulative dose-response curves for morphine analgesia upon chronic neonatal morphine was observed both on P20 and P49. The swim stress-induced analgesia was significantly decreased in neonatal morphine-exposed rats on P29, but not on P49. These data indicate that morphine exposure equivalent to the third trimester of gestation produced prolonged pain hypersensitivity, decreased morphine antinociception, and decreased stress-induced analgesia. The present study illustrates the need to examine the long-term influence of prenatal morphine exposure on pain and analgesia in the human pediatric population.

  15. Fish oil concentrate delays sensitivity to thermal nociception in mice

    Science.gov (United States)

    Veigas, Jyothi M.; Williams, Paul J.; Halade, Ganesh; Rahman, Mizanur M.; Yoneda, Toshiyuki; Fernandes, Gabriel

    2011-01-01

    Fish oil has been used to alleviate pain associated with inflammatory conditions such as rheumatoid arthritis. The anti-inflammatory property of fish oil is attributed to the n-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid. Contrarily, vegetable oils such as safflower oil are rich in n-6 fatty acids which are considered to be mediators of inflammation. This study investigates the effect of n-3 and n-6 fatty acids rich oils as dietary supplements on the thermally induced pain sensitivity in healthy mice. C57Bl/6J mice were fed diet containing regular fish oil, concentrated fish oil formulation (CFO) and safflower oil (SO) for 6 months. Pain sensitivity was measured by plantar test and was correlated to the expression of acid sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1) and c-fos in dorsal root ganglion cells. Significant delay in sensitivity to thermal nociception was observed in mice fed CFO compared to mice fed SO (p<0.05). A significant diminution in expression of ion channels such as ASIC1a (64%), ASIC13 (37%) and TRPV1 (56%) coupled with reduced expression of c-fos, a marker of neuronal activation, was observed in the dorsal root ganglion cells of mice fed CFO compared to that fed SO. In conclusion, we describe here the potential of fish oil supplement in reducing sensitivity to thermal nociception in normal mice. PMID:21345372

  16. Nociceptive DRG neurons express muscle lim protein upon axonal injury.

    Science.gov (United States)

    Levin, Evgeny; Andreadaki, Anastasia; Gobrecht, Philipp; Bosse, Frank; Fischer, Dietmar

    2017-04-04

    Muscle lim protein (MLP) has long been regarded as a cytosolic and nuclear muscular protein. Here, we show that MLP is also expressed in a subpopulation of adult rat dorsal root ganglia (DRG) neurons in response to axonal injury, while the protein was not detectable in naïve cells. Detailed immunohistochemical analysis of L4/L5 DRG revealed ~3% of MLP-positive neurons 2 days after complete sciatic nerve crush and maximum ~10% after 4-14 days. Similarly, in mixed cultures from cervical, thoracic, lumbar and sacral DRG ~6% of neurons were MLP-positive after 2 days and maximal 17% after 3 days. In both, histological sections and cell cultures, the protein was detected in the cytosol and axons of small diameter cells, while the nucleus remained devoid. Moreover, the vast majority could not be assigned to any of the well characterized canonical DRG subpopulations at 7 days after nerve injury. However, further analysis in cell culture revealed that the largest population of MLP expressing cells originated from non-peptidergic IB4-positive nociceptive neurons, which lose their ability to bind the lectin upon axotomy. Thus, MLP is mostly expressed in a subset of axotomized nociceptive neurons and can be used as a novel marker for this population of cells.

  17. Assessment of anti-nociceptive efficacy of costus speciosus rhizome in swiss albino mice.

    Science.gov (United States)

    Bhattacharya, Sanjib; Nagaich, Upendra

    2010-01-01

    Present study attempts to evaluate the anti-nociceptive activity of the aqueous and ethanol extracts of Costus speciosus rhizome (CPA and CPE) in Swiss albino mice. The maceration extracts were evaluated for anti-nociceptive activity by acetic acid-induced writhing and tail flick method in mice. The anti-nociceptive screening revealed significant peripheral anti-nociceptive actions of both extracts against acetic acid induced writhing in mice. Aqueous extract (CPA) significantly inhibited writhes at the dose of 75 and 150 mg/kg body weight, while ethanol extract (CPE) produced significant protection at the dose of 150 mg/kg body weight. However, in tail flick method only the ethanol extract (CPE) showed significant central analgesic action, while aqueous extract was totally ineffective. The present investigation demonstrates that the rhizome extracts of C. speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.

  18. Assessment of anti-nociceptive efficacy of Costus Speciosus rhizome in swiss albino mice

    Directory of Open Access Journals (Sweden)

    Sanjib Bhattacharya

    2010-01-01

    Full Text Available Present study attempts to evaluate the anti-nociceptive activity of the aqueous and ethanol extracts of Costus speciosus rhizome (CPA and CPE in Swiss albino mice. The maceration extracts were evaluated for anti-nociceptive activity by acetic acid-induced writhing and tail flick method in mice. The anti-nociceptive screening revealed significant peripheral anti-nociceptive actions of both extracts against acetic acid induced writhing in mice. Aqueous extract (CPA significantly inhibited writhes at the dose of 75 and 150 mg/kg body weight, while ethanol extract (CPE produced significant protection at the dose of 150 mg/kg body weight. However, in tail flick method only the ethanol extract (CPE showed significant central analgesic action, while aqueous extract was totally ineffective. The present investigation demonstrates that the rhizome extracts of C. speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.

  19. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

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    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

  20. The role of Drosophila Piezo in mechanical nociception.

    Science.gov (United States)

    Kim, Sung Eun; Coste, Bertrand; Chadha, Abhishek; Cook, Boaz; Patapoutian, Ardem

    2012-02-19

    Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo

  1. Modulation of Visceral Nociception, Inflammation and Gastric Mucosal Injury by Cinnarizine

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    Omar M.E. Abdel-Salam

    2007-01-01

    Full Text Available The effect of cinnarizine, a drug used for the treatment of vertigo was assessed in animal models of visceral nociception, inflammation and gastric mucosal injury. Cinnarizine (1.25–20 mg/kg, s.c. caused dose-dependent inhibition of the abdominal constrictions evoked by i.p. injection of acetic acid by 38.7–99.4%. This effect of cinnarizine (2.5 mg/kg was unaffected by co-administration of the centrally acting dopamine D2 receptor antagonists, sulpiride, haloperidol or metoclopramide, the peripherally acting D2 receptor antagonist domperidone, but increased by the D2 receptor agonist bromocryptine and by the non-selective dopamine receptor antagonist chlorpromazine. The antinociception caused by cinnarizine was naloxone insenstive, but enhanced by propranolol, atropine and by yohimbine. The antinociceptive effect of cinnarizine was prevented by co-treatment with the adenosine receptor blocker theophylline or by the ATP-sensitive potassium channel (KATP blocker glibenclamide. Cinnarizine at 2.5 mg/kg reversed the baclofen-induced antinociception. Cinnarizine at 2.5 mg/kg reduced immobility time in the Porsolt’s forced-swimming test by 24%. Cinnarizine inhibited the paw oedema response to carrageenan and reduced gastric mucosal lesions caused by indomethacin in rats. It is suggested that cinnarizine exerts anti-infl ammatory, antinociceptive and gastric protective properties. The mechanism by which cinnarizine modulates pain transmission is likely to involve adenosine receptors and KATP channels.

  2. Nociceptive responses to thermal and mechanical stimulations in awake pigs

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S.

    2013-01-01

    body sizes (30 and 60 kg) were exposed to thermal (CO(2) laser) and mechanical (pressure application measurement device) stimulations to the flank and the hind legs in a balanced order. The median response latency and the type of behavioural response were recorded. RESULTS: Small pigs exhibited...... animal studies in a large species require further examination. This manuscript describes the initial development of a porcine model of cutaneous nociception and focuses on interactions between the sensory modality, body size and the anatomical location of the stimulation site. METHODS: Pigs of different...... significantly lower pain thresholds (shorter latency to response) than large pigs to thermal and mechanical stimulations. Stimulations at the two anatomical locations elicited very distinct sets of behavioural responses, with different levels of sensitivity between the flank and the hind legs. Furthermore...

  3. Interaction of corneal nociceptive stimulation and lacrimal secretion.

    Science.gov (United States)

    Situ, Ping; Simpson, Trefford L

    2010-11-01

    To investigate the interaction between corneal stimuli at different positions and tear secretion and to establish relationships between nociceptive stimuli detection thresholds and stimulated tearing. Using a computerized Belmonte-esthesiometer, mechanical and chemical stimuli, from 0% to 200% of the threshold in 50% steps, were delivered (in random order) to the central and peripheral (approximately 2-mm inside the limbus) cornea during four separate sessions to 15 subjects. Immediately after each stimulus, tear meniscus height (TMH) was measured using optical coherence tomography to quantify the amount of lacrimal secretion, and subjects reported whether they felt tears starting to accumulate in their eyes. Thresholds (50% detection) for detection of tearing were estimated. TMH increased with increasing stimulus intensity (P lacrimation reflex. Central mechanical corneal stimulation is the most effective stimulus-position pairing and appears to be the major sensory driving force for reflex tear secretion by the lacrimal functional unit.

  4. Sertraline inhibits formalin-induced nociception and cardiovascular responses

    Energy Technology Data Exchange (ETDEWEB)

    Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Futuro Neto, H.A. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Pesquisa e Extensão, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil); Pires, J.G.P. [Escola de Medicina da Empresa Brasileira de Ensino, Pesquisa e Extensão, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Gonçalves, W.L.S. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Tiradentes, R.V.; Gouvea, S.A.; Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2011-11-18

    The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8 per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg{sup −1}·day{sup −1}, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

  5. Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

    Science.gov (United States)

    Casey, Kenneth L.

    1999-07-01

    Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

  6. Nociceptive sensations evoked from 'spots' in the skin by mild cooling and heating.

    Science.gov (United States)

    Green, Barry G; Roman, Carolyn; Schoen, Kate; Collins, Hannah

    2008-03-01

    It was recently found that nociceptive sensations (stinging, pricking, or burning) can be evoked by cooling or heating the skin to innocuous temperatures (e.g., 29 and 37 degrees C). Here, we show that this low-threshold thermal nociception (LTN) can be traced to sensitive 'spots' in the skin equivalent to classically defined warm spots and cold spots. Because earlier work had shown that LTN is inhibited by simply touching a thermode to the skin, a spatial search procedure was devised that minimized tactile stimulation by sliding small thermodes (16 and 1mm(2)) set to 28 or 36 degrees C slowly across the lubricated skin of the forearm. The procedure uncovered three types of temperature-sensitive sites (thermal, bimodal, and nociceptive) that contained one or more thermal, nociceptive, or (rarely) bimodal spots. Repeated testing indicated that bimodal and nociceptive sites were less stable over time than thermal sites, and that mechanical contact differentially inhibited nociceptive sensations. Intensity ratings collected over a range of temperatures showed that LTN increased monotonically on heat-sensitive sites but not on cold-sensitive sites. These results provide psychophysical evidence that stimulation from primary afferent fibers with thresholds in the range of warm fibers and cold fibers is relayed to the pain pathway. However, the labile nature of LTN implies that these low-threshold nociceptive inputs are subject to inhibitory controls. The implications of these findings for the roles of putative temperature receptors and nociceptors in innocuous thermoreception and thermal pain are discussed.

  7. 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

  8. Effect of PGD2 on middle meningeal artery and mRNA expression profile of L-PGD2 synthase and DP receptors in trigeminovascular system and other pain processing structures in rat brain

    DEFF Research Database (Denmark)

    Sekeroglu, Aysegül; Jacobsen, Julie Mie; Jansen-Olesen, Inger

    2017-01-01

    Background Prostaglandins (PGs), particularly prostaglandin D2 (PGD2), E2 (PGE2), and I2 (PGI2), are considered to play a role in migraine pain. In humans, infusion of PGD2 causes lesser headache as compared to infusion of PGE2 and PGI2. Follow-up studies in rats have shown that infusion of PGE2...... and PGI2 dilate the middle meningeal artery (MMA), and mRNA for PGE2 and PGI2 receptors is present in rat trigeminovascular system (TVS) and in the brain structures associated with pain. In the present study, we have characterized the dilatory effect of PGD2 on rat MMA and studied the relative m...... tested tissues. DP1 receptor mRNA was expressed maximally in trigeminal ganglion (TG) and in cervical dorsal root ganglion (DRG). Conclusions High expression of DP1 mRNA in the TG and DRG suggest that PGD2 might play a role in migraine pathophysiology. Activation of the DP1 receptor in MMA was mainly...

  9. Anti-nociceptive effect of total alkaloids isolated from the seeds of ...

    African Journals Online (AJOL)

    pretreatment of the animals with naloxone (2 mg/kg) was performed to investigate whether the anti- nociceptive effect .... detecting the absorbance at 618 nm. Arecoline ..... attenuates food allergic responses in ovalbumin- sensitized mice.

  10. 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.

  11. Electrophysiological assessment of nociception in patients with Parkinson's disease : A multi-methods approach

    NARCIS (Netherlands)

    Priebe, Janosch A.; Kunz, Miriam; Morcinek, Christian; Rieckmann, Peter; Lautenbacher, Stefan

    2016-01-01

    Objective: Nociceptive abnormalities indicating increased pain sensitivity have been reported in patients with Parkinson's disease (PD). The disturbances are mostly responsive to dopaminergic (DA) treatment; yet, there are conflicting results. The objective of the present study was to investigate

  12. Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

    Science.gov (United States)

    Patel, Atit A.

    2018-01-01

    ABSTRACT Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity. PMID:29752280

  13. Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

    Science.gov (United States)

    Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

    2018-04-02

    Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

  14. Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

    Directory of Open Access Journals (Sweden)

    Wang Ying-Wei

    2010-01-01

    Full Text Available Abstract Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist and parecoxib (a selective cyclooxygenase-2 inhibitor on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity, while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.

  15. Factors affecting mechanical nociceptive thresholds in healthy sows.

    Science.gov (United States)

    Nalon, Elena; Maes, Dominiek; Piepers, Sofie; Taylor, Polly; van Riet, Miriam M J; Janssens, Geert P J; Millet, Sam; Tuyttens, Frank A M

    2016-05-01

    To describe anatomical and methodological factors influencing mechanical nociceptive thresholds (MNTs) and intra-site variability in healthy sows. Prospective, randomized validation. Eight pregnant, healthy, mixed-parity sows (176-269 kg). Repeated MNT measurements were taken: 1) with a hand-held probe and a limb-mounted actuator connected to a digital algometer; 2) at nine landmarks on the limbs and tail; and 3) at 1 and 3 minute intervals. Data were analysed using linear mixed regression models. The MNTs (±SEM) of the limbs were lower with the probe (14.7 ± 1.2 N) than with the actuator (21.3 ± 1.2 N; p testing compared with day 1 (p < 0.001). The mean CV (±SE) was 38.9% (±1.1%). MNTs and intra-site variability in healthy sows were affected by several factors, indicating that this methodology requires considerable attention to detail. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  16. Regulation of Wnt signaling by nociceptive input in animal models

    Directory of Open Access Journals (Sweden)

    Shi Yuqiang

    2012-06-01

    Full Text Available Abstract Background Central sensitization-associated synaptic plasticity in the spinal cord dorsal horn (SCDH critically contributes to the development of chronic pain, but understanding of the underlying molecular pathways is still incomplete. Emerging evidence suggests that Wnt signaling plays a crucial role in regulation of synaptic plasticity. Little is known about the potential function of the Wnt signaling cascades in chronic pain development. Results Fluorescent immunostaining results indicate that β-catenin, an essential protein in the canonical Wnt signaling pathway, is expressed in the superficial layers of the mouse SCDH with enrichment at synapses in lamina II. In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers. Immunoblotting analysis indicates that both Wnt3a a β-catenin are up-regulated in the SCDH of various mouse pain models created by hind-paw injection of capsaicin, intrathecal (i.t. injection of HIV-gp120 protein or spinal nerve ligation (SNL. Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models. Conclusion Our results suggest that Wnt signaling pathways are regulated by nociceptive input. The activation of Wnt signaling may regulate the expression of spinal central sensitization during the development of acute and chronic pain.

  17. Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

    Science.gov (United States)

    Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

    2017-08-30

    Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a

  18. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword.

    Science.gov (United States)

    Chen, Jun; Lariviere, William R

    2010-10-01

    Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Application of a handheld Pressure Application Measurement device for the characterisation of mechanical nociceptive thresholds in intact pig tails

    DEFF Research Database (Denmark)

    Di Giminiani, Pierpaolo; Sandercock, Dale A.; Malcolm, Emma M.

    2016-01-01

    The assessment of nociceptive thresholds is employed in animals and humans to evaluate changes in sensitivity potentially arising from tissue damage. Its application on the intact pig tail might represent a suitable method to assess changes in nociceptive thresholds arising from tail injury...... to the body was observed (P knowledge, no other...... nociceptive threshold in pig tails. This methodological approach is possibly suitable for assessing changes in tail stump MNTs after tail injury caused by tail docking and biting....

  20. Distinct brain mechanisms support spatial vs temporal filtering of nociceptive information.

    Science.gov (United States)

    Nahman-Averbuch, Hadas; Martucci, Katherine T; Granovsky, Yelena; Weissman-Fogel, Irit; Yarnitsky, David; Coghill, Robert C

    2014-12-01

    The role of endogenous analgesic mechanisms has largely been viewed in the context of gain modulation during nociceptive processing. However, these analgesic mechanisms may play critical roles in the extraction and subsequent utilization of information related to spatial and temporal features of nociceptive input. To date, it remains unknown if spatial and temporal filtering of nociceptive information is supported by similar analgesic mechanisms. To address this question, human volunteers were recruited to assess brain activation with functional magnetic resonance imaging during conditioned pain modulation (CPM) and offset analgesia (OA). CPM provides one paradigm for assessing spatial filtering of nociceptive information while OA provides a paradigm for assessing temporal filtering of nociceptive information. CPM and OA both produced statistically significant reductions in pain intensity. However, the magnitude of pain reduction elicited by CPM was not correlated with that elicited by OA across different individuals. Different patterns of brain activation were consistent with the psychophysical findings. CPM elicited widespread reductions in regions engaged in nociceptive processing such as the thalamus, insula, and secondary somatosensory cortex. OA produced reduced activity in the primary somatosensory cortex but was associated with greater activation in the anterior insula, dorsolateral prefrontal cortex, intraparietal sulcus, and inferior parietal lobule relative to CPM. In the brain stem, CPM consistently produced reductions in activity, while OA produced increases in activity. Conjunction analysis confirmed that CPM-related activity did not overlap with that of OA. Thus, dissociable mechanisms support inhibitory processes engaged during spatial vs temporal filtering of nociceptive information. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Triptans and CGRP blockade – impact on the cranial vasculature

    NARCIS (Netherlands)

    Benemei, S. (Silvia); Cortese, F. (Francesca); Labastida-Ramírez, A. (Alejandro); Marchese, F. (Francesca); Pellesi, L. (Lanfranco); Romoli, M. (Michele); Vollesen, A.L. (Anne Luise); Lampl, C. (Christian); Ashina, M. (Messoud)

    2017-01-01

    textabstractThe trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission

  2. Sensitization of the Nociceptive System in Complex Regional Pain Syndrome

    Science.gov (United States)

    Diedrichs, Carolina; Baron, Ralf; Gierthmühlen, Janne

    2016-01-01

    Background Complex regional pain syndrome type I (CRPS-I) is characterized by sensory, motor and autonomic abnormalities without electrophysiological evidence of a nerve lesion. Objective Aims were to investigate how sensory, autonomic and motor function change in the course of the disease. Methods 19 CRPS-I patients (17 with acute, 2 with chronic CRPS, mean duration of disease 5.7±8.3, range 1–33 months) were examined with questionnaires (LANSS, NPS, MPI, Quick DASH, multiple choice list of descriptors for sensory, motor, autonomic symptoms), motor and autonomic tests as well as quantitative sensory testing according to the German Research Network on Neuropathic Pain at two visits (baseline and 36±10.6, range 16–53 months later). Results CRPS-I patients had an improvement of sudomotor and vasomotor function, but still a great impairment of sensory and motor function upon follow-up. Although pain and mechanical detection improved upon follow-up, thermal and mechanical pain sensitivity increased, including the contralateral side. Increase in mechanical pain sensitivity and loss of mechanical detection were associated with presence of ongoing pain. Conclusions The results demonstrate that patients with CRPS-I show a sensitization of the nociceptive system in the course of the disease, for which ongoing pain seems to be the most important trigger. They further suggest that measured loss of function in CRPS-I is due to pain-induced hypoesthesia rather than a minimal nerve lesion. In conclusion, this article gives evidence for a pronociceptive pain modulation profile developing in the course of CRPS and thus helps to assess underlying mechanisms of CRPS that contribute to the maintenance of patients’ pain and disability. PMID:27149519

  3. Sensitization of the Nociceptive System in Complex Regional Pain Syndrome.

    Directory of Open Access Journals (Sweden)

    Maren Reimer

    Full Text Available Complex regional pain syndrome type I (CRPS-I is characterized by sensory, motor and autonomic abnormalities without electrophysiological evidence of a nerve lesion.Aims were to investigate how sensory, autonomic and motor function change in the course of the disease.19 CRPS-I patients (17 with acute, 2 with chronic CRPS, mean duration of disease 5.7±8.3, range 1-33 months were examined with questionnaires (LANSS, NPS, MPI, Quick DASH, multiple choice list of descriptors for sensory, motor, autonomic symptoms, motor and autonomic tests as well as quantitative sensory testing according to the German Research Network on Neuropathic Pain at two visits (baseline and 36±10.6, range 16-53 months later.CRPS-I patients had an improvement of sudomotor and vasomotor function, but still a great impairment of sensory and motor function upon follow-up. Although pain and mechanical detection improved upon follow-up, thermal and mechanical pain sensitivity increased, including the contralateral side. Increase in mechanical pain sensitivity and loss of mechanical detection were associated with presence of ongoing pain.The results demonstrate that patients with CRPS-I show a sensitization of the nociceptive system in the course of the disease, for which ongoing pain seems to be the most important trigger. They further suggest that measured loss of function in CRPS-I is due to pain-induced hypoesthesia rather than a minimal nerve lesion. In conclusion, this article gives evidence for a pronociceptive pain modulation profile developing in the course of CRPS and thus helps to assess underlying mechanisms of CRPS that contribute to the maintenance of patients' pain and disability.

  4. Central nervous system mast cells in peripheral inflammatory nociception

    Directory of Open Access Journals (Sweden)

    Ellmeier Wilfried

    2011-06-01

    Full Text Available Abstract Background Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation. Results Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia. Conclusion The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.

  5. Sida cordifolia leaf extract reduces the orofacial nociceptive response in mice.

    Science.gov (United States)

    Bonjardim, L R; Silva, A M; Oliveira, M G B; Guimarães, A G; Antoniolli, A R; Santana, M F; Serafini, M R; Santos, R C; Araújo, A A S; Estevam, C S; Santos, M R V; Lyra, A; Carvalho, R; Quintans-Júnior, L J; Azevedo, E G; Botelho, M A

    2011-08-01

    In this study, we describe the antinociceptive activity of the ethanol extract (EE), chloroform (CF) and methanol (MF) fractions obtained from Sida cordifolia, popularly known in Brazil as "malva branca" or "malva branca sedosa". Leaves of S. cordifolia were used to produce the crude ethanol extract and after CF and MF. Experiments were conducted on Swiss mice using the glutamate and formalin-induced orofacial nociception. In the formalin test, all doses of EE, CF and MF significantly reduced the orofacial nociception in the first (p < 0.001) and second phase (p < 0.001), which was also naloxone-sensitive. In the glutamate-induced nociception test, only CF and MF significantly reduced the orofacial nociceptive behavior with inhibition percentage values of 48.1% (100 mg/kg, CF), 56.1% (200 mg/kg, CF), 66.4% (400 mg/kg, CF), 48.2 (200 mg/kg, MF) and 60.1 (400 mg/kg, MF). Furthermore, treatment of the animals with EE, CF and MF was not able to promote motor activity changes. These data demonstrate that S. cordifolia has a pronounced antinociceptive activity on orofacial nociception. However, pharmacological and chemical studies are necessary in order to characterize the responsible mechanisms for this antinociceptive action and also to identify other bioactive compounds present in S. cordifolia. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

    Directory of Open Access Journals (Sweden)

    Aaron D. Mickle

    2016-11-01

    Full Text Available Specialized receptors belonging to the transient receptor potential (TRP family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics.

  7. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  8. Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses.

    Science.gov (United States)

    Elfenbein, Johanna R; Sanchez, L Chris; Robertson, Sheilah A; Cole, Cynthia A; Sams, Richard

    2009-03-01

    To evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations. Nonrandomized, experimental trial. Five adult horses, each with a permanent gastric cannula weighing 534 +/- 46 kg. Visceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose-to-ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 microg kg(-1)) was administered intravenously. Data were analyzed by means of a three-factor anova with fixed factors of treatment and time and random factor of horse. When a significant time x treatment interaction was detected, differences were compared with a simple t-test or Bonferroni t-test. Significance was set at p Detomidine produced a significant, dose-dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose-dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 microg kg(-1) for 15 minutes and for at least 165 minutes with 20 microg kg(-1). Duodenal distension threshold was significantly increased at 15 minutes for the 20 microg kg(-1) dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes. Detomidine caused a longer period of visceral anti-nociception as determined by CRD but a shorter period of anti-nociception as determined by DD than has been previously reported. The lack of somatic anti-nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut-off of the testing device.

  9. Learned control over spinal nociception in patients with chronic back pain.

    Science.gov (United States)

    Krafft, S; Göhmann, H-D; Sommer, J; Straube, A; Ruscheweyh, R

    2017-10-01

    Descending pain inhibition suppresses spinal nociception, reducing nociceptive input to the brain. It is modulated by cognitive and emotional processes. In subjects with chronic pain, it is impaired, possibly contributing to pain persistence. A previously developed feedback method trains subjects to activate their descending inhibition. Participants are trained to use cognitive-emotional strategies to reduce their spinal nociception, as quantified by the nociceptive flexor reflex (RIII reflex), under visual feedback about their RIII reflex size. The aim of the present study was to test whether also subjects with chronic back pain can achieve a modulation of their descending pain inhibition under RIII feedback. In total, 33 subjects with chronic back pain received either true (n = 18) or sham RIII feedback (n = 15), 15 healthy control subjects received true RIII feedback. All three groups achieved significant RIII suppression, largest in controls (to 76 ± 26% of baseline), intermediate in chronic back pain subjects receiving true feedback (to 82 ± 13%) and smallest in chronic back pain subjects receiving sham feedback (to 89 ± 14%, all p chronic pain subjects receiving true feedback significantly improved their descending inhibition over the feedback training, quantified by the conditioned pain modulation effect (test pain reduction of baseline before training: to 98 ± 26%, after: to 80 ± 21%, p chronic back pain can achieve a reduction of their spinal nociception and improve their descending pain inhibition under RIII feedback training. Subjects with chronic back pain can learn to control their spinal nociception, quantified by the RIII reflex, when they receive feedback about the RIII reflex. © 2017 European Pain Federation - EFIC®.

  10. Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

    Science.gov (United States)

    Liu, Peng; Xing, Bo; Chu, Zheng; Liu, Fei; Lei, Gang; Zhu, Li; Gao, Ya; Chen, Teng; Dang, Yong-Hui

    2017-07-01

    Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Anti-nociceptive activity of Pereskia bleo Kunth. (Cactaceae) leaves extracts.

    Science.gov (United States)

    Abdul-Wahab, Ikarastika Rahayu; Guilhon, Carolina Carvalho; Fernandes, Patricia Dias; Boylan, Fabio

    2012-12-18

    Local communities in Malaysia consume Pereskia bleo Kunth. (Cactaceae) leaves as raw vegetables or as a concoction and drink as a tea to treat diabetes, hypertension, rheumatism, cancer-related diseases, inflammation, gastric pain, ulcers, and for revitalizing the body. To evaluate anti-nociceptive activity of the extracts and vitexin, isolated for the first time in this species, in two analgesic models; formalin-induced licking and acetic acid-induced abdominal writhing. Three and a half kilos of P. bleo leaves were extracted using Soxhlet apparatus with ethanol for 72 h. The crude ethanol extract was treated with activated charcoal overnight and subjected to a liquid-liquid partition yielding hexane, dichloromethane, ethyl acetate and butanol extracts. All extracts, including the crude ethanol and vitexin isolated from the ethyl acetate partition were tested for peripheral anti-nociceptive activity using formalin test and acetic acid-induced abdominal writhing, besides having their acute toxicity assays performed. The phytochemical analyses resulted in the isolation of vitexin (1), β-sitosterol glucoside (2) and β-sitosterol (3) isolated from the ethyl acetate, dichloromethane and hexane extracts, respectively. This is the first time vitexin and β-sitosterol glucoside are isolated from this species. The anti-nociceptive activities for all extracts were only moderate. Vitexin, which was isolated from the ethyl acetate extract did not show any activity in all models tested when used alone at the same concentration as it appears in the extract. This study showed that all the extracts possess moderate anti-nociceptive activity. Vitexin is not the compound responsible for the anti-nociceptive effect in the ethyl acetate extract. Further investigations are needed to identify the compound(s) that might be responsible for the anti-nociceptive activity in this plant. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats.

    Directory of Open Access Journals (Sweden)

    Luiz Fabio Dimov

    Full Text Available Transcranial direct current stimulation (tDCS is an emerging, noninvasive technique of neurostimulation for treating pain. However, the mechanisms and pathways involved in its analgesic effects are poorly understood. Therefore, we investigated the effects of direct current stimulation (DCS on thermal and mechanical nociceptive thresholds and on the activation of the midbrain periaqueductal gray (PAG and the dorsal horn of the spinal cord (DHSC in rats; these central nervous system areas are associated with pain processing. Male Wistar rats underwent cathodal DCS of the motor cortex and, while still under stimulation, were evaluated using tail-flick and paw pressure nociceptive tests. Sham stimulation and naive rats were used as controls. We used a randomized design; the assays were not blinded to the experimenter. Immunoreactivity of the early growth response gene 1 (Egr-1, which is a marker of neuronal activation, was evaluated in the PAG and DHSC, and enkephalin immunoreactivity was evaluated in the DHSC. DCS did not change the thermal nociceptive threshold; however, it increased the mechanical nociceptive threshold of both hind paws compared with that of controls, characterizing a topographical effect. DCS decreased the Egr-1 labeling in the PAG and DHSC as well as the immunoreactivity of spinal enkephalin. Altogether, the data suggest that DCS disinhibits the midbrain descending analgesic pathway, consequently inhibiting spinal nociceptive neurons and causing an increase in the nociceptive threshold. This study reinforces the idea that the motor cortex participates in the neurocircuitry that is involved in analgesia and further clarifies the mechanisms of action of tDCS in pain treatment.

  13. Measuring cutaneous thermal nociception in group-housed pigs using laser technique - effects of laser power output

    DEFF Research Database (Denmark)

    Herskin, Mette S.; Ladevig, Jan; Arendt-Nielsen, Lars

    2009-01-01

    Nociceptive testing is a valuable tool in the development of pharmaceutical products, for basic nociceptive research, and for studying changes in pain sensitivity is investigated after inflammatory states or nerve injury. However, in pigs only very limited knowledge about nociceptive processes...... nociceptive stimulation from a computer-controlled CO2-laser beam applied to either the caudal part of the metatarsus on the hind legs or the shoulder region of gilts. In Exp. 1, effects of laser power output (0, 0.5, 1, 1.5 and 2 W) on nociceptive responses toward stimulation on the caudal aspects...... of the metatarsus were examined using 15 gilts kept in one group and tested in individual feeding stalls after feeding. Increasing the power output led to gradually decreasing latency to respond (P 

  14. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

    OpenAIRE

    Birol Muhammet Er; İsmail Serhat Kocamanoğlu; Ayhan Bozkurt; Sırrı Bilge; Erhan Çetin Çetinoğlu

    2016-01-01

    Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. ...

  15. Response characteristics of pruriceptive and nociceptive trigeminoparabrachial tract neurons in the rat

    NARCIS (Netherlands)

    N.A. Jansen (Nico A.); G.J. Giesler (Glenn J.)

    2015-01-01

    textabstractWe tested the possibility that the trigeminoparabrachial tract (VcPbT), a projection thought to be importantly involved in nociception, might also contribute to sensation of itch. In anesthetized rats, 47 antidromically identified VcPbT neurons with receptive fields involving the cheek

  16. Nurses assessing pain with the Nociception Coma Scale: interrater reliability and validity

    NARCIS (Netherlands)

    Vink, Peter; Eskes, Anne Maria; Lindeboom, Robert; van den Munckhof, Pepijn; Vermeulen, Hester

    2014-01-01

    The Nociception Coma Scale (NCS) is a pain observation tool, developed for patients with disorders of consciousness (DOC) due to acquired brain injury (ABI). The aim of this study was to assess the interrater reliability of the NCS and NCS-R among nurses for the assessment of pain in ABI patients

  17. Anti-nociceptive and anti-inflammatory properties of the ethanolic ...

    African Journals Online (AJOL)

    Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. ... Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be ...

  18. 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

  19. Pain sensation and nociceptive reflex excitability in surgical patients and human volunteers

    DEFF Research Database (Denmark)

    Dahl, J B; Erichsen, C J; Fuglsang-Frederiksen, A

    1992-01-01

    Pain threshold, nociceptive flexion reflex (NFR) threshold and responses to suprathreshold stimulation were investigated in 15 female patients (mean age 32 yr (range 22-48 yr)) before and 68 (range 48-96) h after gynaecological laparotomy. Control measurements were performed in 17 healthy human v...

  20. Local anesthetic effect of docosahexaenoic acid on the nociceptive jaw-opening reflex in rats.

    Science.gov (United States)

    Mitome, Kazuki; Takehana, Shiori; Oshima, Katsuo; Shimazu, Yoshihito; Takeda, Mamoru

    2018-02-23

    Although docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1-5 x threshold). At 3 x threshold, local administration of DHA (0.1, 10 and 25 mM) dose-dependently inhibited the dEMG response, and lasted 40 min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10 min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25 mM) was almost equal to the local anesthetic, 1% lidocaine (37 mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

  1. Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex

    DEFF Research Database (Denmark)

    Fischer, I W; Gram, M; Hansen, T M

    2017-01-01

    solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty...

  2. Innocuous cooling can produce nociceptive sensations that are inhibited during dynamic mechanical contact.

    Science.gov (United States)

    Green, Barry G; Pope, Jennifer V

    2003-02-01

    In a previous study of the heat grill illusion, sensations of burning and stinging were sometimes reported when the skin was cooled by as little as 2 degrees C. Informal tests subsequently indicated that these nociceptive sensations were experienced if cooling occurred when the stimulating thermode rested on the skin, but not when the thermode was cooled and then touched to the skin. In experiment 1 subjects judged the intensity of thermal (cold/warm) and nociceptive (burning/stinging) sensations when the volar surface of the forearm was cooled to 25 degrees C (1) via a static thermode (Static condition), or (2) via a cold thermode touched to the skin (Dynamic condition). The total area of stimulation was varied from 2.6 to 10.4 cm(2) to determine if the occurrence of nociceptive sensations depended upon stimulus size. Burning/stinging was rated 10.3 times stronger in the Static condition than in the Dynamic condition, and this difference did not vary significantly with stimulus size. In experiment 2, thermal and nociceptive sensations were measured during cooling to just 31 degrees, 29 degrees or 27 degrees C, and data were obtained on the frequency at which different sensation qualities were experienced. Stinging was the most frequently reported nociceptive quality in the Static condition, and stinging and burning were both markedly reduced in the Dynamic condition. In experiment 3 we tested the possibility that dynamic contact might have inhibited burning and stinging not because of mechanical contact per se, but rather because dynamic contact caused higher rates of cooling. However, varying cooling rate over a tenfold range (-0.5 degrees to -5.0 degrees /s) had no appreciable effect on the frequency of stinging and burning. Overall, the data show that mild cooling can produce nociceptive sensations that are suppressed under conditions of dynamic mechanical contact. The latter observation suggests that cold is perceived differently during active contact with

  3. Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis

    Directory of Open Access Journals (Sweden)

    Klaas Ilka C

    2011-05-01

    Full Text Available Abstract Background Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables. Methods Seven Danish Holstein-Friesian cows were kept in tie-stalls, where the E. coli associated mastitis was induced and laser stimulations were conducted. Measurements of rectal temperature, somatic cell counts, white blood cell counts and E. coli counts were conducted. Furthermore, scores were given for anorexia, local udder inflammation and milk appearance to quantify the local and systemic disease response. In order to quantify the nociceptive threshold, behavioral responses toward cutaneous NLS applied to six skin areas at the tarsus/metatarsus and udder hind quarters were registered at evening milking on day 0 (control and days 1, 2, 3, 6 and 10 after experimental induction of mastitis. Results All clinical and paraclinical variables were affected by the induced mastitis. All cows were clinically ill on days 1 and 2. The cows responded behaviorally toward the NLS. For hind leg stimulation, the proportion of cows responding by stepping was higher on day 0 than days 3 and 6, and the frequency of leg movements after laser stimulation tended to decrease on day 1 compared to the other days. After udder stimulation, the proportion of cows responding by stepping was higher on day 1 than on all other days of testing. Significant correlations between the clinical and paraclinical variables of disease and the behavioral responses toward nociceptive stimulation were found. Conclusions Changes in behavioral responses coincide with peaks in local and systemic signs of E

  4. Consequences of a human TRPA1 genetic variant on the perception of nociceptive and olfactory stimuli.

    Directory of Open Access Journals (Sweden)

    Michael Schütz

    Full Text Available BACKGROUND: TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity. METHODS: Olfactory function and nociception was compared between carriers (n = 38 and non-carriers (n = 43 of TRPA1 variant rs11988795 G>A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2. RESULTS: Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2 were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049. Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.1±1.5 versus 12.3±1.6 correct discriminations and indicated a higher intensity of the H2S stimuli (29.2±13.2 versus 21±12.8 mm VAS, p = 0.006, which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced. CONCLUSIONS: The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.

  5. Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

    Science.gov (United States)

    Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

    2017-07-01

    Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals

  6. Neuroglial Transmission

    DEFF Research Database (Denmark)

    Gundersen, Vidar; Storm-Mathisen, Jon; Bergersen, Linda Hildegard

    2015-01-01

    as a signaling substance recently shown to act on specific lactate receptors in the brain. Complementing neurotransmission at a synapse, neuroglial transmission often implies diffusion of the transmitter over a longer distance and concurs with the concept of volume transmission. Transmission from glia modulates...... synaptic neurotransmission based on energetic and other local conditions in a volume of tissue surrounding the individual synapse. Neuroglial transmission appears to contribute significantly to brain functions such as memory, as well as to prevalent neuropathologies....

  7. Possible effects of mobilisation on acute post-operative pain and nociceptive function after total knee arthroplasty

    DEFF Research Database (Denmark)

    Lunn, T H; Kristensen, B B; Gaarn-Larsen, L

    2012-01-01

    anaesthesia and analgesia underwent an exercise (mobilisation) strategy on the first post-operative morning consisting of 25-m walking twice, with a 20-min interval. Pain was assessed at rest and during passive hip and knee flexion before, and 5 and 20 min after walk, as well as during walk. Nociceptive......BACKGROUND: Experimental studies in animals, healthy volunteers, and patients with chronic pain suggest exercise to provide analgesia in several types of pain conditions and after various nociceptive stimuli. To our knowledge, there is no data on the effects of exercise on pain and nociceptive...... function in surgical patients despite early mobilisation being an important factor to enhance recovery. We therefore investigated possible effects of mobilisation on post-operative pain and nociceptive function after total knee arthroplasty (TKA). METHODS: Thirty patients undergoing TKA under standardised...

  8. Mechanisms of G Protein-Coupled Estrogen Receptor-Mediated Spinal Nociception

    DEFF Research Database (Denmark)

    Deliu, Elena; Brailoiu, G. Cristina; Arterburn, Jeffrey B.

    2012-01-01

    . Cytosolic calcium concentration elevates faster and with higher amplitude following G-1 intracellular microinjections compared to extracellular exposure, suggesting subcellular GPER functionality. Thus, GPER activation results in spinal nociception, and the downstream mechanisms involve cytosolic calcium......Human and animal studies suggest that estrogens are involved in the processing of nociceptive sensory information and analgesic responses in the central nervous system. Rapid pronociceptive estrogenic effects have been reported, some of which likely involve G protein-coupled estrogen receptor (GPER......) activation. Membrane depolarization and increases in cytosolic calcium and reactive oxygen species (ROS) levels are markers of neuronal activation, underlying pain sensitization in the spinal cord. Using behavioral, electrophysiological, and fluorescent imaging studies, we evaluated GPER involvement...

  9. Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

    Science.gov (United States)

    Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

    2015-08-01

    Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

  10. Differential inhibitory effect on human nociceptive skin senses induced by local stimulation of thin cutaneous fibers.

    Science.gov (United States)

    Nilsson, H J; Schouenborg, J

    1999-03-01

    It is known that stimulation of thin cutaneous nerve fibers can induce long lasting analgesia through both supraspinal and segmental mechanisms, the latter often exhibiting restricted receptive fields. On this basis, we recently developed a new method, termed cutaneous field stimulation (CFS), for localized stimulation of A delta and C fibers in the superficial part of the skin. In the present study, we have evaluated the effects of CFS on non-nociceptive and nociceptive skin senses. We compared the effects of CFS with those of conventional transcutaneous electrical nerve stimulation (TENS), known to preferentially activate coarse myelinated fibers. A battery of sensory tests were made on the right volar forearm of 20 healthy subjects. CFS (16 electrodes, 4 Hz per electrode, 1 ms, up to 0.8 mA) and TENS (100 Hz, 0.2 ms, up to 26 mA) applied either on the right volar forearm (homotopically), or on the lower right leg (heterotopically) were used as conditioning stimulation for 25 min. The tactile threshold was not affected by either homo- or heterotopical CFS or TENS. The mean thresholds for detecting warming or cooling of the skin were increased by 0.4-0.9 degrees C after homo- but not heterotopical CFS and TENS. Regarding nociceptive skin senses, homo- but not heterotopical CFS, markedly reduced CO2-laser evoked A delta- and C fiber mediated heat pain to 75 and 48% of control, respectively, and mechanically evoked pain to 73% of control. Fabric evoked prickle, was not affected by CFS. Neither homo- nor heterotopical TENS induced any marked analgesic effects. It is concluded that different qualities of nociception can be differentially controlled by CFS.

  11. Impact of carprofen administration on stress and nociception responses of calves to cautery dehorning.

    Science.gov (United States)

    Stock, M L; Barth, L A; Van Engen, N K; Millman, S T; Gehring, R; Wang, C; Voris, E A; Wulf, L W; Labeur, Léa; Hsu, W H; Coetzee, J F

    2016-02-01

    The objective of this study was to investigate the effects of carprofen administered immediately before cautery dehorning on nociception and stress. Forty Holstein calves aged approximately 6 to 8 wk old were either placebo treated and sham dehorned ( = 10) or cautery dehorned following administration of carprofen (1.4 mg/kg) subcutaneously ( = 10) or orally ( = 10) or a subcutaneous and oral placebo ( = 10) in a randomized, controlled trial. All animals were given a cornual nerve block using lidocaine before dehorning. Response variables including mechanical nociception threshold, ocular temperature, heart rate, and respiratory rate were measured before and following cautery dehorning for 96 h. Blood samples were also collected over 96 h following dehorning and analyzed for plasma cortisol and substance P concentrations by RIA. Plasma carprofen concentration and ex vivo PGE concentrations were also determined for this time period. Average daily gain was calculated for 7 d after dehorning. Data were analyzed using a linear mixed effects model with repeated measures, controlling for baseline values by their inclusion as a covariate in addition to planned contrasts. Dehorning was associated with decreased nociception thresholds throughout the study and a stress response immediately after dehorning, following the loss of local anesthesia, and 48 h after dehorning compared with sham-dehorned calves. Carprofen was well absorbed after administration and reached concentrations that inhibited ex vivo PGE concentrations for 72 h (subcutaneous) and 96 h (oral) compared with placebo-treated calves ( Carprofen-treated calves tended to be less sensitive ( = 0.097) to nociceptive threshold tests. Overall, at the dosing regimen studied, the effect of carprofen on sensitivity and stress following cautery dehorning was minimal. Consideration of route of administration and dose determination studies may be warranted.

  12. Molecular Basis of TRPA1 Regulation in Nociceptive Neurons. A Review

    Czech Academy of Sciences Publication Activity Database

    Kádková, Anna; Synytsya, Viktor; Krůšek, Jan; Zímová, Lucie; Vlachová, Viktorie

    2017-01-01

    Roč. 66, č. 3 (2017), s. 425-439 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA15-15839S; GA MZd(CZ) NV16-28784A Institutional support: RVO:67985823 Keywords : transient receptor potential ankyrin 1 * bradykinin * structure- function * nociception * post-translational modifications * signaling pathways Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

  13. Ovariectomy results in variable changes in nociception, mood and depression in adult female rats.

    Directory of Open Access Journals (Sweden)

    Li-Hong Li

    Full Text Available Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX, a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%-induced nociceptive responses (such as elevating and licking or biting during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact. Using formalin-induced conditioned place avoidance (F-CPA, which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA. In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.

  14. Neuro chemical characteristic of structures of nociceptive system athyperthyroid function of the thyroid gland

    Directory of Open Access Journals (Sweden)

    O. M. Demchenko

    2015-06-01

    Full Text Available The papercomprises the study of the conditionofpro-antioxidantprocesses in the formationso fnociceptivesystem (cerebral cortex, hippocampus, stem and thalamus in the presence of the experiment al induced hyperthyroidism. It was found that nociceptive irritation (laparotomy on the background of hyper thyroidism had not pronounced effect on the content of diene conjugates (DC and malondialdehyde. The level of enzymes of antioxidant system of superoxidedismutase (SOD and glutathioneperoxidase (GPO decreased.

  15. Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

    Science.gov (United States)

    Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

    2014-06-01

    Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

  16. Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture

    OpenAIRE

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Sun, Yuan; Wei, Tzuping; Clark, David J; Kingery, Wade S

    2015-01-01

    Tibia fracture in rodents induces substance P (SP)-dependent keratinocyte activation and inflammatory changes in the hindlimb, similar to those seen in complex regional pain syndrome (CRPS). In animal pain models spinal glial cell activation results in nociceptive sensitization. This study tested the hypothesis that limb fracture triggers afferent C-fiber SP release in the dorsal horn, resulting in chronic glia activation and central sensitization. At 4 weeks after tibia fracture and casting ...

  17. Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions.

    Science.gov (United States)

    Yegutkin, Gennady G; Guerrero-Toro, Cindy; Kilinc, Erkan; Koroleva, Kseniya; Ishchenko, Yevheniia; Abushik, Polina; Giniatullina, Raisa; Fayuk, Dmitriy; Giniatullin, Rashid

    2016-09-01

    Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide-inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca(2+) transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pro-nociceptive effect of ATP in meningeal nerves was reproduced by α,β-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain.

  18. The Purinergic System and Glial Cells: Emerging Costars in Nociception

    Directory of Open Access Journals (Sweden)

    Giulia Magni

    2014-01-01

    Full Text Available It is now well established that glial cells not only provide mechanical and trophic support to neurons but can directly contribute to neurotransmission, for example, by release and uptake of neurotransmitters and by secreting pro- and anti-inflammatory mediators. This has greatly changed our attitude towards acute and chronic disorders, paving the way for new therapeutic approaches targeting activated glial cells to indirectly modulate and/or restore neuronal functions. A deeper understanding of the molecular mechanisms and signaling pathways involved in neuron-to-glia and glia-to-glia communication that can be pharmacologically targeted is therefore a mandatory step toward the success of this new healing strategy. This holds true also in the field of pain transmission, where the key involvement of astrocytes and microglia in the central nervous system and satellite glial cells in peripheral ganglia has been clearly demonstrated, and literally hundreds of signaling molecules have been identified. Here, we shall focus on one emerging signaling system involved in the cross talk between neurons and glial cells, the purinergic system, consisting of extracellular nucleotides and nucleosides and their membrane receptors. Specifically, we shall summarize existing evidence of novel “druggable” glial purinergic targets, which could help in the development of innovative analgesic approaches to chronic pain states.

  19. Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.

    Directory of Open Access Journals (Sweden)

    G Gregory Neely

    Full Text Available The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species.

  20. Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat.

    Science.gov (United States)

    Aloisi, A M; Steenbergen, H L; van de Poll, N E; Farabollini, F

    1994-05-01

    The sex-dependent effects of acute restraint (RT) on nociceptive and pituitary-adrenal responses were investigated in the rat. In a first experiment, the effect of 30 min RT on pain sensitivity was evaluated through repeated use of the tail withdrawal test during and after treatment. RT induced an increase in the nociceptive threshold, i.e., analgesia, in males and females, but the duration and time-course of this effect varied between sexes. The latencies returned to approximately control values in females in the second half of RT, but in males they remained higher for the whole period of RT and immediately afterwards. Twenty-four hours later, males displayed longer latencies than controls in response to simple reexposure to the environment. In a second experiment, ACTH and corticosterone plasma levels were measured immediately after 15 or 30 min of RT. ACTH and corticosterone were higher in restrained animals than in controls after both periods of treatment, and in both sexes; however, females showed higher basal and stress corticosterone levels than males. The role played by corticosteroids in the nociceptive responses of the two sexes is discussed.

  1. Effects of magnetic field exposure on open field behaviour and nociceptive responses in mice.

    Science.gov (United States)

    Del Seppia, Cristina; Mezzasalma, Lorena; Choleris, Elena; Luschi, Paolo; Ghione, Sergio

    2003-09-15

    Results of previous studies have shown that nociceptive sensitivity in male C57 mice is enhanced by exposure to a regular 37 Hz or an irregularly varying (field. In order to test whether these fields affect more generally mouse behaviour, we placed Swiss CD-1 mice in a novel environment (open field test) and exposed them for 2 h to these two different magnetic field conditions. Hence, we analysed how duration and time course of various behavioural patterns (i.e. exploration, rear, edge chew, self-groom, sit, walk and sleep) and nociceptive sensitivity had been affected by such exposure. Nociceptive sensitivity was significantly greater in magnetically treated mice than in controls. The overall time spent in exploratory activities was significantly shorter in both magnetically treated groups (time), than in controls (42%). Conversely, the time spent in sleeping was markedly longer in the treated groups (both 27% of total time) than in controls (11%). These results suggest that exposure to altered magnetic fields induce a more rapid habituation to a novel environment.

  2. Construction of a Global Pain Systems Network Highlights Phospholipid Signaling as a Regulator of Heat Nociception

    Science.gov (United States)

    Mair, Norbert; Racz, Ildiko; Milinkeviciute, Giedre; Meixner, Arabella; Nayanala, Swetha; Griffin, Robert S.; Belfer, Inna; Dai, Feng; Smith, Shad; Diatchenko, Luda; Marengo, Stefano; Haubner, Bernhard J.; Novatchkova, Maria; Gibson, Dustin; Maixner, William; Pospisilik, J. Andrew; Hirsch, Emilio; Whishaw, Ian Q.; Zimmer, Andreas; Gupta, Vaijayanti; Sasaki, Junko; Kanaho, Yasunori; Sasaki, Takehiko; Kress, Michaela; Woolf, Clifford J.; Penninger, Josef M.

    2012-01-01

    The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species. PMID:23236288

  3. Pruritic and Nociceptive Sensations and Dysesthesias From a Spicule of Cowhage

    Science.gov (United States)

    LaMotte, R. H.; Shimada, S. G.; Green, B. G.; Zelterman, D.

    2009-01-01

    Although the trichomes (spicules) of a pod of cowhage (Mucuna pruriens) are known to evoke a histamine-independent itch that is mediated by a cysteine protease, little is known of the itch and accompanying nociceptive sensations evoked by a single spicule and the enhanced itch and pain that can occur in the surrounding skin. The tip of a single spicule applied to the forearm of 45 subjects typically evoked 1) itch accompanied by nociceptive sensations (NS) of pricking/stinging and, to a lesser extent, burning, and 2) one or more areas of cutaneous dysesthesia characterized by hyperknesis (enhanced itch to pricking) with or without alloknesis (itch to stroking) and/or hyperalgesia (enhanced pricking pain). Itch could occur in the absence of NS or one or more dysesthesias but very rarely the reverse. The peak magnitude of sensation was positively correlated for itch and NS and increased (exhibited spatial summation) as the number of spicules was increased within a spatial extent of 6 cm but not 1 cm. The areas of dysesthesia did not exhibit spatial summation. We conclude that itch evoked by a punctate chemical stimulus can co-exist with NS and cutaneous dysesthesias as may occur in clinical pruritus. However, cowhage itch was not always accompanied by NS or dysesthesia nor was a momentary change in itch necessarily accompanied by a similar change in NS or vice versa. Thus there may be separate neural coding mechanisms for itch, nociceptive sensations, and each type of dysesthesia. PMID:19144738

  4. Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats

    Science.gov (United States)

    Todorovic, Slobodan M; Rastogi, A J; Jevtovic-Todorovic, Vesna

    2003-01-01

    Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage- and ligand-gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood. Therefore, we studied the potential analgesic effects of commonly used anticonvulsant agents in peripheral nociception. We injected anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used anticonvulsants such as voltage-gated Na+ channel blockers, phenytoin and carbamazepine, and voltage-gated Ca2+ channel blockers, gabapentin and ethosuximide, induced dose-dependent analgesia in the injected paw, with ED50 values of 0.30, 0.32 and 8, 410 μg per 100 μl, respectively. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of anticonvulsants that elicited local analgesia. Hill slope coefficients for the tested anticonvulsants indicate that the dose–response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide. Our data strongly suggest that cellular targets like voltage-gated Na+ and Ca2+ channels, similar to those that mediate the effects of anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied anticonvulsants that block voltage-gated Na+ and Ca2+ channels may be useful analgesics. PMID:12970103

  5. Phytochemical Screening and Anti-nociceptive Properties of the Ethanolic Leaf Extract of Trema Cannabina Lour

    Directory of Open Access Journals (Sweden)

    Hira Arpona

    2013-02-01

    Full Text Available Purpose: The present study was designed to investigate the anti-nociceptive activity of ethanolic leaf extract of Trema cannabina Lour (family: Cannabaceae in experimental animal models. Methods: The anti-nociceptive action was carried out against two types of noxious stimuli, thermal (hot plate and tail immersion tests and chemical (acetic acid-induced writhing in mice. Results: Phytochemical analysis of crude extract indicated the presence of reducing sugar, tannins, steroid and alkaloid types of secondary metabolites. Crude extract of T. cannabina (500 mg/kg dose showed maximum time needed for the response against thermal stimuli (6.79±0.15 seconds which is comparable to diclofenac sodium (8.26±0.14 seconds in the hot plate test. Hot tail immersion test also showed similar results as in hot plate test. At the dose of 250 and 500 mg/kg body weight, the extract showed significantly and in a dose-dependent (p<0.001 reduction in acetic acid induced writhing in mice with a maximum effect of 47.56% reduction at 500 mg/kg dose comparable to that of diclofenac sodium (67.07% at 25 mg/kg. Conclusion: The obtained results tend to suggest the Anti-nociceptive activity of ethanolic leaf extract of Trema cannabina and thus provide the scientific basis for the traditional uses of this plant part as a remedy for pain.

  6. Validation of a thermal threshold nociceptive model in bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Couture, Émilie L; Monteiro, Beatriz P; Aymen, Jessica; Troncy, Eric; Steagall, Paulo V

    2017-05-01

    To validate a thermal threshold (TT) nociceptive model in bearded dragons (Pogona vitticeps) and to document TT changes after administration of morphine. A two-part randomized, blinded, controlled, experimental study. Five adult bearded dragons (242-396 g). A TT device delivered a ramped nociceptive stimulus (0.6 °C second -1 ) to the medial thigh until a response (leg kick/escape behavior) was observed or maximum (cut-off) temperature of 62 °C was reached. In phase I, period 1, six TT readings were determined at 20 minute intervals for evaluation of repeatability. Two of these readings were randomly assigned to be sham to assess specificity of the behavioral response. The same experiment was repeated 2 weeks later (period 2) to test reproducibility. In phase II, animals were administered either intramuscular morphine (10 mg kg -1 ) or saline 0.9%. TTs (maximum 68 °C) were determined before and 2, 4, 8, 12 and 24 hours after treatment administration. Data were analyzed using one-way anova (temporal changes and repeatability) and paired t tests (reproducibility and treatment comparisons) using Bonferroni correction (p dragons. TT nociceptive testing detected morphine administration and may be suitable for studying opioid regimens in bearded dragons. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  7. Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice

    Directory of Open Access Journals (Sweden)

    Jackson Roberto Guedes da Silva Almeida

    2013-01-01

    Full Text Available Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P<0.01 reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.. When the hot plate test was conducted, borneol (in higher dose produced an inhibition (P<0.05 of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.

  8. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  9. Prediction of immediate postoperative pain using the analgesia/nociception index: a prospective observational study.

    Science.gov (United States)

    Boselli, E; Bouvet, L; Bégou, G; Dabouz, R; Davidson, J; Deloste, J-Y; Rahali, N; Zadam, A; Allaouchiche, B

    2014-04-01

    The analgesia/nociception index (ANI) is derived from heart rate variability, ranging from 0 (maximal nociception) to 100 (maximal analgesia), to reflect the analgesia/nociception balance during general anaesthesia. This should be correlated with immediate postoperative pain in the post-anaesthesia care unit (PACU). The aim of this study was to evaluate the performance of ANI measured at arousal from general anaesthesia to predict immediate postoperative pain on arrival in PACU. Two hundred patients undergoing ear, nose, and throat or lower limb orthopaedic surgery with general anaesthesia using an inhalational agent and remifentanil were included in this prospective observational study. The ANI was measured immediately before tracheal extubation and pain intensity was assessed within 10 min of arrival in PACU using a 0-10 numerical rating scale (NRS). The relationship between ANI and NRS was assessed using linear regression. A receiver-operating characteristic (ROC) curve was used to evaluate the performance of ANI to predict NRS>3. A negative linear relationship was observed between ANI immediately before extubation and NRS on arrival in PACU. Using a threshold of 3 were both 86% with 92% negative predictive value, corresponding to an area under the ROC curve of 0.89. The measurement of ANI immediately before extubation after inhalation-remifentanil anaesthesia was significantly associated with pain intensity on arrival in PACU. The performance of ANI for the prediction of immediate postoperative pain is good and may assist physicians in optimizing acute pain management. ClinicalTrials.gov NCT01796249.

  10. Cognitive aspects of nociception and pain: bridging neurophysiology with cognitive psychology.

    Science.gov (United States)

    Legrain, V; Mancini, F; Sambo, C F; Torta, D M; Ronga, I; Valentini, E

    2012-10-01

    The event-related brain potentials (ERPs) elicited by nociceptive stimuli are largely influenced by vigilance, emotion, alertness, and attention. Studies that specifically investigated the effects of cognition on nociceptive ERPs support the idea that most of these ERP components can be regarded as the neurophysiological indexes of the processes underlying detection and orientation of attention toward the eliciting stimulus. Such detection is determined both by the salience of the stimulus that makes it pop out from the environmental context (bottom-up capture of attention) and by its relevance according to the subject's goals and motivation (top-down attentional control). The fact that nociceptive ERPs are largely influenced by information from other sensory modalities such as vision and proprioception, as well as from motor preparation, suggests that these ERPs reflect a cortical system involved in the detection of potentially meaningful stimuli for the body, with the purpose to respond adequately to potential threats. In such a theoretical framework, pain is seen as an epiphenomenon of warning processes, encoded in multimodal and multiframe representations of the body, well suited to guide defensive actions. The findings here reviewed highlight that the ERPs elicited by selective activation of nociceptors may reflect an attentional gain apt to bridge a coherent perception of salient sensory events with action selection processes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. Effect of Gmelina arborea Roxb in experimentally induced inflammation and nociception

    Directory of Open Access Journals (Sweden)

    Yogesh A Kulkarni

    2013-01-01

    Full Text Available Background: Gmelina arborea Roxb (Verbenaceae, also known as "Gambhari", is an important medicinal plant in the Ayurveda. There are no meticulous scientific reports on effect of the plant on inflammation and pain. Objective: To study the anti-inflammatory and anti-nociceptive properties of aqueous extracts (AE and methanol extracts (ME of G. arborea. Materials and Methods: The AE and ME of stembark of G. arborea was prepared by cold maceration and Soxhlet extraction technique respectively. Anti-inflammatory activity was determined in Wistar albino rats in a model of acute plantar inflammation induced by carrageenan. The anti-nociceptive activity was evaluated by using hot plate test and writhing test in Swiss albino mice. Significant differences between the experimental groups were assessed by analysis of variance. Results: AE and ME at dose of 500 mg/kg showed maximum inhibition in carrageenan induced inflammation up to 30.15 and 31.21% respectively. In hot plate test, the AE and ME showed the maximum response of 8.8 ± 0.97 (P < 0.01 and 8.2 ± 1.24 (P < 0.01 respectively at dose of 500 mg/kg when compared with control. AE showed maximum inhibition of writhing response (84.3% as compared to ME (77.9% in writhing test at a dose of 500 mg/kg. Conclusion: The findings suggested that G. arborea possess significant anti-inflammatory and anti-nociceptive activities.

  12. Transmission issues

    International Nuclear Information System (INIS)

    Bradford, J.; Wilson, L.; Thon, S.; Millar, N.

    2005-01-01

    This session on transmission issues focused on the role that transmission plays in electricity markets and the importance of getting the market structure right in terms of generation divestiture with buy back contracts, demand side responsive programs, transmission upgrades and long term contracts. The difficulties of distinguishing between market power and scarcity were examined along with some of the complications that ensue if transmission experiences congestion, as exemplified by the August 2003 blackout in eastern North America. The presentations described the best ways to handle transmission issues, and debated whether transmission should be deregulated or follow market forces. Issues of interconnections and reliability of connections were also debated along with the attempt to integrate renewables into the grid. Some presentations identified what new transmission must be built and what must be done to ensure that transmission gets built. The challenges and business opportunities for transmission in Alberta were discussed with reference to plans to invest in new infrastructure, where it is going outside of the province and how it works with other jurisdictions. Manitoba's Conawapa Hydro Project and its 2000 MW tie line to Ontario was also discussed. Some examples of non-optimal use of interconnections in Europe were also discussed in an effort to learn from these mistakes and avoid them in Canada. tabs., figs

  13. Linkage between increased nociception and olfaction via a SCN9A haplotype.

    Directory of Open Access Journals (Sweden)

    Dirk Heimann

    Full Text Available BACKGROUND AND AIMS: Mutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity. METHODS: SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14 or rs6746030C>T (R1150W; n = 21 were compared with non-carriers (n = 40. Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli. RESULTS: The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1, 1 allele: 10.6±2.6 (n = 34, 2 alleles: 9.5±2.1 (n = 40. The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m(2, 1 allele: 29.8±10.4 N/m(2, 2 alleles: 33.5±10.2 N/m(2. CONCLUSIONS: The findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level.

  14. Transmission eigenvalues

    Science.gov (United States)

    Cakoni, Fioralba; Haddar, Houssem

    2013-10-01

    In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator [1]. The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium [2]. In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989 [3] and Rynne and Sleeman in 1991 [4] showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission

  15. Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain

    Science.gov (United States)

    Ferré, S.; Diamond, I.; Goldberg, S.R.; Yao, L.; Hourani, S.M.O.; Huang, Z.L.; Urade, Y.; Kitchen, I.

    2007-01-01

    Adenosine A2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A2A receptors. A2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A2A receptor knockout mice suggest that A2A receptor antagonists might have some therapeutic potential in pain states, in particular where

  16. Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

    Science.gov (United States)

    Saitoh, Chikashi; Yokoyama, Hitoshi; Chancellor, Michael B.; de Groat, William C.; Yoshimura, Naoki

    2009-01-01

    Aims Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (ip) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats. Methods Female Sprague-Dawley rats were used. Cystitis was induced by ip injection of CYP (100 and 200mg/kg) or intravesical instillation of acetone (10, 30 and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an evans blue (EB) dye leakage technique. Results CYP (100mg/kg, ip) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200mg/kg, ip) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected. Conclusions These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity. PMID:19618450

  17. Quantifying Transmission.

    Science.gov (United States)

    Woolhouse, Mark

    2017-07-01

    Transmissibility is the defining characteristic of infectious diseases. Quantifying transmission matters for understanding infectious disease epidemiology and designing evidence-based disease control programs. Tracing individual transmission events can be achieved by epidemiological investigation coupled with pathogen typing or genome sequencing. Individual infectiousness can be estimated by measuring pathogen loads, but few studies have directly estimated the ability of infected hosts to transmit to uninfected hosts. Individuals' opportunities to transmit infection are dependent on behavioral and other risk factors relevant given the transmission route of the pathogen concerned. Transmission at the population level can be quantified through knowledge of risk factors in the population or phylogeographic analysis of pathogen sequence data. Mathematical model-based approaches require estimation of the per capita transmission rate and basic reproduction number, obtained by fitting models to case data and/or analysis of pathogen sequence data. Heterogeneities in infectiousness, contact behavior, and susceptibility can have substantial effects on the epidemiology of an infectious disease, so estimates of only mean values may be insufficient. For some pathogens, super-shedders (infected individuals who are highly infectious) and super-spreaders (individuals with more opportunities to transmit infection) may be important. Future work on quantifying transmission should involve integrated analyses of multiple data sources.

  18. Force transmissibility versus displacement transmissibility

    Science.gov (United States)

    Lage, Y. E.; Neves, M. M.; Maia, N. M. M.; Tcherniak, D.

    2014-10-01

    It is well-known that when a single-degree-of-freedom (sdof) system is excited by a continuous motion of the foundation, the force transmissibility, relating the force transmitted to the foundation to the applied force, equals the displacement transmissibility. Recent developments in the generalization of the transmissibility to multiple-degree-of-freedom (mdof) systems have shown that similar simple and direct relations between both types of transmissibility do not appear naturally from the definitions, as happens in the sdof case. In this paper, the authors present their studies on the conditions under which it is possible to establish a relation between force transmissibility and displacement transmissibility for mdof systems. As far as the authors are aware, such a relation is not currently found in the literature, which is justified by being based on recent developments in the transmissibility concept for mdof systems. Indeed, it does not appear naturally, but the authors observed that the needed link is present when the displacement transmissibility is obtained between the same coordinates where the applied and reaction forces are considered in the force transmissibility case; this implies that the boundary conditions are not exactly the same and instead follow some rules. This work presents a formal derivation of the explicit relation between the force and displacement transmissibilities for mdof systems, and discusses its potential and limitations. The authors show that it is possible to obtain the displacement transmissibility from measured forces, and the force transmissibility from measured displacements, opening new perspectives, for example, in the identification of applied or transmitted forces. With this novel relation, it becomes possible, for example, to estimate the force transmissibility matrix with the structure off its supports, in free boundary conditions, and without measuring the forces. As far as force identification is concerned, this

  19. Data transmission

    National Research Council Canada - National Science Library

    Tugal, Dogan A; Tugal, Osman

    1989-01-01

    This updated second edition provides working answers to today's critical questions about designing and managing all types of data transmission systems and features a new chapter on local area networks (LANs...

  20. Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae).

    Science.gov (United States)

    Damascena, N P; Souza, M T S; Almeida, A F; Cunha, R S; Damascena, N P; Curvello, R L; Lima, A C B; Almeida, E C V; Santos, C C S; Dias, A S; Paixão, M S; Souza, L M A; Quintans Júnior, L J; Estevam, C S; Araujo, B S

    2014-01-01

    The anti-nociceptive and antioxidant activities of the Anadenantheracolubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 μg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 μg/mL) of lipid peroxidation caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly (p < 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly (p < 0.001) reduced by up to 79% at 400 mg/kg, while 56-60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100-400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms.

  1. Effect of butorphanol on thermal nociceptive threshold in healthy pony foals.

    Science.gov (United States)

    McGowan, K T; Elfenbein, J R; Robertson, S A; Sanchez, L C

    2013-07-01

    Pain management is an important component of foal nursing care, and no objective data currently exist regarding the analgesic efficacy of opioids in foals. To evaluate the somatic antinociceptive effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy foals. Our hypothesis was that thermal nociceptive threshold would increase following i.v. butorphanol in a dose-dependent manner in both neonatal and older pony foals. Seven healthy neonatal pony foals (age 1-2 weeks), and 11 healthy older pony foals (age 4-8 weeks). Five foals were used during both age periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt) and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover design with at least 2 days between treatments. Response variables included thermal nociceptive threshold, skin temperature and behaviour score. Data within each age period were analysed using a 2-way repeated measures ANOVA, followed by a Holm-Sidak multiple comparison procedure if warranted. There was a significant (P<0.05) increase in thermal threshold, relative to Time 0, following butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant time or treatment effects were apparent for skin temperature. Significant time, but not treatment, effects were evident for behaviour score in both age groups. Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly increased thermal nociceptive threshold in neonatal and older foals without apparent adverse behavioural effects. Butorphanol shows analgesic potential in foals for management of somatic painful conditions. © 2012 EVJ Ltd.

  2. Reliability and validity of a brief method to assess nociceptive flexion reflex (NFR) threshold.

    Science.gov (United States)

    Rhudy, Jamie L; France, Christopher R

    2011-07-01

    The nociceptive flexion reflex (NFR) is a physiological tool to study spinal nociception. However, NFR assessment can take several minutes and expose participants to repeated suprathreshold stimulations. The 4 studies reported here assessed the reliability and validity of a brief method to assess NFR threshold that uses a single ascending series of stimulations (Peak 1 NFR), by comparing it to a well-validated method that uses 3 ascending/descending staircases of stimulations (Staircase NFR). Correlations between the NFR definitions were high, were on par with test-retest correlations of Staircase NFR, and were not affected by participant sex or chronic pain status. Results also indicated the test-retest reliabilities for the 2 definitions were similar. Using larger stimulus increments (4 mAs) to assess Peak 1 NFR tended to result in higher NFR threshold estimates than using the Staircase NFR definition, whereas smaller stimulus increments (2 mAs) tended to result in lower NFR threshold estimates than the Staircase NFR definition. Neither NFR definition was correlated with anxiety, pain catastrophizing, or anxiety sensitivity. In sum, a single ascending series of electrical stimulations results in a reliable and valid estimate of NFR threshold. However, caution may be warranted when comparing NFR thresholds across studies that differ in the ascending stimulus increments. This brief method to assess NFR threshold is reliable and valid; therefore, it should be useful to clinical pain researchers interested in quickly assessing inter- and intra-individual differences in spinal nociceptive processes. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    Science.gov (United States)

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

  4. Psychophysics of a nociceptive test in the mouse: ambient temperature as a key factor for variation.

    Directory of Open Access Journals (Sweden)

    Ivanne Pincedé

    Full Text Available The mouse is increasingly used in biomedical research, notably in behavioral neurosciences for the development of tests or models of pain. Our goal was to provide the scientific community with an outstanding tool that allows the determination of psychophysical descriptors of a nociceptive reaction, which are inaccessible with conventional methods: namely the true threshold, true latency, conduction velocity of the peripheral fibers that trigger the response and latency of the central decision-making process.Basically, the procedures involved heating of the tail with a CO(2 laser, recording of tail temperature with an infrared camera and stopping the heating when the animal reacted. The method is based mainly on the measurement of three observable variables, namely the initial temperature, the heating rate and the temperature reached at the actual moment of the reaction following random variations in noxious radiant heat. The initial temperature of the tail, which itself depends on the ambient temperature, very markedly influenced the behavioral threshold, the behavioral latency and the conduction velocity of the peripheral fibers but not the latency of the central decision-making.We have validated a psychophysical approach to nociceptive reactions for the mouse, which has already been described for rats and Humans. It enables the determination of four variables, which contribute to the overall latency of the response. The usefulness of such an approach was demonstrated by providing new fundamental findings regarding the influence of ambient temperature on nociceptive processes. We conclude by challenging the validity of using as "pain index" the reaction time of a behavioral response to an increasing heat stimulus and emphasize the need for a very careful control of the ambient temperature, as a prevailing environmental source of variation, during any behavioral testing of mice.

  5. Tramadol effects on clinical variables and the mechanical nociceptive threshold in horses

    OpenAIRE

    Franco,Leandro Guimarães; Moreno,Juan Carlos Duque; Teixeira Neto,Antônio Raphael; Souza,Moisés Caetano e; Silva,Luiz Antônio Franco da

    2014-01-01

    This study assessed the clinical effects and the mechanical antinociceptive potential of intravenous (IV) tramadol in horses.A blinded and randomized study was designed with 7 horses treated with 1 (Tr1), 2 (Tr2) or 3 (Tr3) mg kg-1 of tramadol IV. The heart rate, respiratory rate (fR), arterial pressure, degree of sedation, gastrointestinal motility (GI), behavior changes and the mechanical nociceptive threshold (MNT) were evaluated. The MNT was determined with von Frey device method.Tr3 had ...

  6. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

    Science.gov (United States)

    Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

    2015-07-01

    Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. The role of protease-activated receptor type 2 in nociceptive signaling and pain

    Czech Academy of Sciences Publication Activity Database

    Mrózková, Petra; Paleček, Jiří; Špicarová, Diana

    2016-01-01

    Roč. 65, č. 3 (2016), s. 357-367 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12058; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA15-11138S; GA MŠk(CZ) LH15279; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : protease-activated receptor (PAR2) * signaling pathways * nociception * pain * spinal cord Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

  8. Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats.

    Science.gov (United States)

    Reese, Jeremy N; Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-04-15

    This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex. Copyright © 2015 the American Physiological Society.

  9. Suppression of thermal and chemical nociception in rats by methanol extract and its sub-fraction from lantana camara

    International Nuclear Information System (INIS)

    Simjee, S.U.; Perveen, H.; Zehra, S.Q.

    2016-01-01

    The traditional use of Lantana camara (Verbenaceae) is reported to include anti-nociceptive, antimicrobial, and immunosuppressant activity. To our knowledge no systematic study has been carried out on the anti-nociceptive activity of L. camara. The present study was designed to delineate the analgesic activity of L. camara extract and its fractions to elucidate the traditional belief in the painkilling effects. Experimental models employed were thermal and chemical-induced nociception assays. After initial screening of the methanol extract and its fractions prepared from the aerial parts of the plant, the dose of 50,100 and 200 mg/kg were selected and route of administration was i.p. The test samples were tested against a reference drug indomethacine (i.p. 5 mg/kg). The observations were made at 15, 30, 60, and 120 seconds following the administration of the samples or reference drug. Experiments on naloxone antagonism were conducted to determine involvement of opioid receptors. Compared to concurrent controls, a significant anti-nociceptive activity was observed in methanol extract LC (ED50 50 mg/kg, P < 0.002) and its sub-fractions LCEA-AQ (ED50 50 mg/kg, P < 0.004), LCEA (ED50 100 mg/kg, P < 0.004) and LCEA-PEI (ED50 100 mg/kg, P < 0.005). No apparent acute toxicity was observed in any test groups. The anti-nociceptive activity was not precipitated by naloxone antagonism indicating that these fractions do not act through opioid receptors. The methanol extract and active fractions of Lantana camara possess anti-nociceptive activity. Further investigations are needed to elucidate the mechanism of its action. (author)

  10. Anti-inflammatory and anti-nociceptive activities of methanol extract from aerial part of Phlomis younghusbandii Mukerjee.

    Directory of Open Access Journals (Sweden)

    Qiu-Shi Wang

    Full Text Available This study was designed to investigate the anti-inflammatory and anti-nociceptive activity of the methanol extract from the aerial part of Phlomis younghusbandii (MEAP and to explore the possible related mechanisms. Anti-inflammatory effects of MEAP were evaluated by using the ear edema test induced by dimethylbenzene and vascular permeability test induced by acetic acid. Anti-nociceptive activities of MEAP were evaluated by the chemical nociception in models of acetic acid-induced writhing and formalin-induced hind paw licking, and by the thermal nociception in hot plate tests. Mechanisms of MEAP activities also were explored by evaluating expression levels of TNF-α, IL-6 and iNOS induced by LPS using real-time fluorogenic PCR and expression of COX-2 using Western blotting and an open-field test. The results indicated that the MEAP administered orally could significantly decrease ear edema induced by dimethylbenzene and increase vascular permeability induced by acetic acid. Additionally, the nociceptions induced by acetic acid and formalin were significantly inhibited. The anti-nociceptive effect could not be decreased by naloxone in the formalin test, and MEAP did not affect the normal autonomic activities of mice. Expression levels of pro-inflammatory cytokines (TNF-α, IL-6, iNOS induced by LPS were decreased obviously by treatment with MEAP. Furthermore, COX-2 expression in the spinal dorsal horns of the pain model mice induced by formalin was significantly down-regulated by MEAP. In conclusion, MEAP has significant anti-inflammatory and antinociceptive activities, and the mechanisms may be related to the down-regulated expression of TNF-α, IL-6, iNOS and COX-2.

  11. Electrical transmission

    Energy Technology Data Exchange (ETDEWEB)

    Sayers, D P

    1960-05-01

    After briefly tracing the history of electricity transmission, trends in high voltage transmission and experiments being conducted on 650 kV are discussed. 5000 miles of the U.K. grid are operated at 132 kV and 1000 at 275 kV, ultimately to provide a super grid at 380 kV. Problems are insulation, radio interference and the cost of underground lines (16 times that of overhead lines). Also considered are the economics of the grid as a means of transporting energy and as a means of spreading the peak load over the power stations in the most efficient manner. Finally, the question of amenities is discussed.

  12. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats.

    Science.gov (United States)

    Birol Muhammet, Er; Kocamanoğlu, İsmail Serhat; Bozkurt, Ayhan; Bilge, Sırrı; Çetinoğlu, Erhan Çetin

    2016-05-01

    Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Animal experimentation. Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L): Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM): Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD): Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D): Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (pdexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (pdexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

  13. Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis.

    Science.gov (United States)

    Greaves, Erin; Grieve, Kelsey; Horne, Andrew W; Saunders, Philippa T K

    2014-09-01

    Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens. The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons. The study was performed using human tissue analysis and cell culture. The study was conducted at a university research institute. Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18). mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens. TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P endometriosis lesions (P endometriosis (P endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

  14. Distinct brain systems mediate the effects of nociceptive input and self-regulation on pain.

    Directory of Open Access Journals (Sweden)

    Choong-Wan Woo

    2015-01-01

    Full Text Available Cognitive self-regulation can strongly modulate pain and emotion. However, it is unclear whether self-regulation primarily influences primary nociceptive and affective processes or evaluative ones. In this study, participants engaged in self-regulation to increase or decrease pain while experiencing multiple levels of painful heat during functional magnetic resonance imaging (fMRI imaging. Both heat intensity and self-regulation strongly influenced reported pain, but they did so via two distinct brain pathways. The effects of stimulus intensity were mediated by the neurologic pain signature (NPS, an a priori distributed brain network shown to predict physical pain with over 90% sensitivity and specificity across four studies. Self-regulation did not influence NPS responses; instead, its effects were mediated through functional connections between the nucleus accumbens and ventromedial prefrontal cortex. This pathway was unresponsive to noxious input, and has been broadly implicated in valuation, emotional appraisal, and functional outcomes in pain and other types of affective processes. These findings provide evidence that pain reports are associated with two dissociable functional systems: nociceptive/affective aspects mediated by the NPS, and evaluative/functional aspects mediated by a fronto-striatal system.

  15. Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings

    Science.gov (United States)

    Passmore, Gayle M.; Reilly, Joanne M.; Thakur, Matthew; Keasberry, Vanessa N.; Marsh, Stephen J.; Dickenson, Anthony H.; Brown, David A.

    2012-01-01

    M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 μM XE991 sensitized Aδ- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32°C in many Aδ-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on Aδ-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive Aδ-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991. PMID:22593734

  16. Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings

    Directory of Open Access Journals (Sweden)

    Gayle M. Passmore

    2012-05-01

    Full Text Available M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 µM XE991 sensitised Adelta- but not C-fibres to noxious heat stimulation and induced spontaneous, ongoing activity at 32ºC in many Adelta-fibres. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on Adelta-fibre peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive Adelta-fibre responses and provide a rationale for the nocifensive behaviours that arise following intraplantar injection of the M-channel blocker XE991.

  17. Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

    Science.gov (United States)

    Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

    2017-11-01

    Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Organization of sensory input to the nociceptive-specific cutaneous trunk muscle reflex in rat, an effective experimental system for examining nociception and plasticity

    Science.gov (United States)

    Petruska, Jeffrey C.; Barker, Darrell F.; Garraway, Sandra M.; Trainer, Robert; Fransen, James W.; Seidman, Peggy A.; Soto, Roy G.; Mendell, Lorne M.; Johnson, Richard D.

    2013-01-01

    Detailed characterization of neural circuitries furthers our understanding of how nervous systems perform specific functions and enables the use of those systems to test hypotheses. We have characterized the sensory input to the cutaneous trunk muscle (CTM; also cutaneus trunci (rat) or cutaneus maximus (mouse)) reflex (CTMR), which manifests as a puckering of the dorsal thoracolumbar skin and is selectively driven by noxious stimuli. CTM electromyography (EMG) and neurogram recordings in naïve rats revealed that CTMR responses were elicited by natural stimuli and electrical stimulation of all segments from C4 to L6, a much greater extent of segmental drive to the CTMR than previously described. Stimulation of some subcutaneous paraspinal tissue can also elicit this reflex. Using a selective neurotoxin, we also demonstrate differential drive of the CTMR by trkA-expressing and non-expressing small diameter afferents. These observations highlight aspects of the organization of the CTMR system which make it attractive for studies of nociception and anesthesiology and plasticity of primary afferents, motoneurons, and the propriospinal system. We use the CTMR system to qualitatively and quantitatively demonstrate that experimental pharmacological treatments can be compared to controls applied either to the contralateral side or to another segment, with the remaining segments providing controls for systemic or other treatment effects. These data indicate the potential for using the CTMR system as both an invasive and non-invasive quantitative assessment tool providing improved statistical power and reduced animal use. PMID:23983104

  19. Effects of awareness and nociception on heart rate variability during general anaesthesia

    International Nuclear Information System (INIS)

    Huhle, R; Zaunseder, S; Malberg, H; Burghardt, M; Koch, T; Heller, A R; Wessel, N

    2012-01-01

    During anaesthesia awareness and nociception are serious complications that may further lead to haemodynamic instability. Specific monitoring of depth of hypnosis and depth of analgesia based on heart rate variability (HRV) analysis is eligible to improve patient safety and reduce efforts in post-operative care. Consequently, in this analysis we assess the applicability of HRV parameters during surgical interventions with standardized intravenous propofol-remifentanil-anaesthesia. Peri-operative electrocardiograms were recorded from cardiovascular stable patients (ASA Score I/II, N = 32, age: 36.4 ± 11.23 a, BMI: 25.2 ± 3.16) scheduled for trauma and dentofacial surgery. HRV time- and frequency-domain parameters, measures of complexity and nonlinear dynamics were compared by analysing longitudinally distributed 300 s intervals preceding/following induction of anaesthesia (BL–I1), intubation (I1–I2) and extubation (E1–E2). Mean value (meanNN) and standard deviation (sdNN) of the heart rate are influenced in BL–I1 (p < 0.001), I1–I2 (p < 0.05) and E1–E2 (p < 0.001). The number of forbidden words of symbolic dynamics changes significantly for BL–I1 (p < 0.001) and not for I1–I2 and E1–E2 (p > 0.05). Probability of low-variability POLVAR10 is significantly altered in all comparisons (BL–I1: Δ = 0.032, p < 0.01, I1–I2: Δ = 0.12, p < 0.05, E1–E2: Δ = 0.169, p < 0.01) but especially during nociception. While standard time-domain parameters lacked selectivity, parameters of symbolic dynamics appear to be specifically influenced by changes in depth of hypnosis and nociception, respectively. However, the lack of steady-state ventilation/breathing in this study needs to be considered in future research. To be used for clinical anaesthesia monitoring our results have to be prospectively validated in clinical studies. (paper)

  20. Changes in the nitric oxide system in the shore crab Hemigrapsus sanguineus (Crustacea, Decapoda) CNS induced by a nociceptive stimulus.

    Science.gov (United States)

    Dyuizen, Inessa V; Kotsyuba, Elena P; Lamash, Nina E

    2012-08-01

    Using NADPH-diaphorase (NADPH-d) histochemistry, inducible nitric oxide synthase (iNOS)-immunohistochemistry and immunoblotting, we characterized the nitric oxide (NO)-producing neurons in the brain and thoracic ganglion of a shore crab subjected to a nociceptive chemical stimulus. Formalin injection into the cheliped evoked specific nociceptive behavior and neurochemical responses in the brain and thoracic ganglion of experimental animals. Within 5-10 min of injury, the NADPH-d activity increased mainly in the neuropils of the olfactory lobes and the lateral antenna I neuropil on the side of injury. Later, the noxious-induced expression of NADPH-d and iNOS was detected in neurons of the brain, as well as in segmental motoneurons and interneurons of the thoracic ganglion. Western blotting analysis showed that an iNOS antiserum recognized a band at 120 kDa, in agreement with the expected molecular mass of the protein. The increase in nitrergic activity induced by nociceptive stimulation suggests that the NO signaling system may modulate nociceptive behavior in crabs.

  1. Modulation of melanocortin- induced changes in spinal nociception by µ-opioid receptor agonist and antagonist in neuropathic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Starowitcz, K.; Przewlocki, R.; Przewlocka, B.

    2002-01-01

    Co-localization of opioid and melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that melanocortins might play a role in nociceptive processes. In the present studies, we aimed to

  2. The effect of social isolation, gender and familiarity with the experimental procedure on tests of porcine nociceptive thresholds

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Stausholm, Julie S.; Viitasaari, Eliina

    2015-01-01

    Objective To investigate the effects of habituation and isolation on mechanical nociceptive thresholds in pigs at the pelvic limbs and at the tail. Study design Prospective randomized multifactorial study. Animals Thirty-two healthy castrated male (experiment 1), and 12 castrated male and 12 female...

  3. Anti-inflammatory and anti-nociceptive activities of methanolic leaf extract of Indigofera cassioides Rottl. Ex. DC.

    Directory of Open Access Journals (Sweden)

    Raju Senthil Kumar

    2013-01-01

    Conclusions: All the results obtained revealed that the extract MEIC showed potent anti-inflammatory and anti-nociceptive activity against all the tested models and the results obtained were comparable with the standards used. The activity of the extract may be due to the presence of terpenoids, flavonoids and other phytochemicals.

  4. Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

    Science.gov (United States)

    Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

    2011-07-01

    Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

  5. Can preoperative electrical nociceptive stimulation predict acute pain after groin herniotomy?

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Hansen, J.B.; Kehlet, H.

    2008-01-01

    Preoperative identification of patients at risk for high-intensity postoperative pain may be used to predict patients at risk for development of a persistent pain state and allocate patients to more intensive specific pain therapy. Preoperative pain threshold to electrocutaneus stimulation has...... repair. The correlation between the pain data for electrical stimulation was compared with the postoperative pain during the first week in 165 patients, whereof 3 were excluded. Preoperative electrical pain detection threshold and electrical pain tolerance threshold did not correlate to postoperative...... pain (rho = -0.13, P = .09, and rho = -1.2, P = .4, respectively. PERSPECTIVE: Although preoperative electrical nociceptive stimulation may predict patients at risk of high-intensity acute pain after other surgical procedures, this was not the case in groin hernia repair patients receiving concomitant...

  6. Long-Term Effects of Neonatal Pain and Stress on Reactivity of the Nociceptive System.

    Science.gov (United States)

    Butkevich, I P; Mikhailenko, V A

    2016-10-01

    The influence of inflammatory pain and/or weaning stress at different terms of neonatal development on functional activity of the nociceptive system during adulthood was studied in rats. Repeated stress in 1-2-day-old rat pups (a premature baby model) enhanced pain sensitivity to peripheral inflammation in both males and females. Repeated inflammatory pain experienced by male pups aged 1-2 or 7-8 days (models of preterm and full-term baby), even in presence of mother, enhanced pain behavior under conditions of repeated inflammatory pain in adulthood. Pain sensitivity in adult animals before (hot plate test) and after formation of the inflammatory focus (formalin test) depended on the age when the animals were subjected to the injury, type of exposure, and on animal sex. The priority data obtained by us will help to understand the mechanisms of long-term effects of early injuries and are important for pediatricians and neonatologists.

  7. Characterization of nociceptive behavioural responses in the awake pig following UV–B-induced inflammation

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars J.; Herskin, Mette S

    2014-01-01

    due to its great homology with humans. Methods The skin in the flank of awake pigs was irradiated by a UV-B light source (1 J/cm2) and changes in thermal and mechanical sensitivity 24 and 48 h following irradiation were measured via assessment of nociceptive behaviours. Results Thermal sensitivity...... skin site than at the control site 24 and 48 h following irradiation (P UV-B irradiation (P = 0.092). Following the inflammatory challenge, the mechanical sensitivity was higher at the site...... of irradiation compared with the control skin at both 24 and 48 h (P UV-B inflammation in porcine skin, but they were not capable of providing a clear indication...

  8. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

    Directory of Open Access Journals (Sweden)

    Birol Muhammet Er

    2016-06-01

    Full Text Available Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. Methods: Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L: Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM: Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD: Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D: Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. Results: The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (p<0.01, all others. In the groups using dexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (p<0.01. Conclusion: Intrathecal dexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

  9. The Anti-Nociceptive Effect of Aloe. Vera Aqueous Extract in Fructose-Fed Male Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Shahraki

    2010-05-01

    Full Text Available A B S T R A C T Introduction: Aloe Vera extract is used as an anti-inflammatory and anti-bradikinin agent in laboratory animals. The aim of this survey was to evaluate the ant-nociceptive effect of A. Vera aqueous extract in fructose-fed male rats. Methods: Forty-five Wistar-Albino male rats were equally and randomly divided into five groups including sham operated and four test groups. Sham operated group consumed tap water and the test groups consumed fructoseenriched water. Test groups 2, 3 and 4 additionally received, 0, 100, 150 and 200 mg/kg of A. Vera extract, respectively, whereas the other test group received distilled water daily. Tail flick reaction time, serum glucose and oral glucose tolerance test (OGTT were measured. The results were analyzed by SPSS software using ANOVA and Tukey tests. Results were expressed as mean ± SD. Statistical differences were considered significant at p<0.05. Results: The results showed that tail flick reaction time significantly increased in test group 3 which received 200 mg/kg A. Vera extract comparing with that of sham operated group. However, OGTT and serum glucose value were significantly increased in all fructose-fed male rats comparing with those of sham operated group. Discussion: These results indicated that A. Vera aqueous extract can affect tail flick reaction time in fructose-fed male rats. Further studies are required to show the exact mechanism of anti-nociceptive effect of A. Vera extract.

  10. Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in Mice.

    Directory of Open Access Journals (Sweden)

    Sonja M Mueller-Tribbensee

    Full Text Available Various transient receptor potential (TRP channels in sensory neurons contribute to the transduction of mechanical stimuli in the colon. Recently, even the cold-sensing menthol receptor TRPM(melastatin8 was suggested to be involved in murine colonic mechano-nociception.To analyze the roles of TRPM8, TRPA1 and TRPV4 in distension-induced colonic nociception and pain, TRP-deficient mice and selective pharmacological blockers in wild-type mice (WT were used. Visceromotor responses (VMR to colorectal distension (CRD in vivo were recorded and distension/pressure-induced CGRP release from the isolated murine colon ex vivo was measured by EIA.Distension-induced colonic CGRP release was markedly reduced in TRPA1-/- and TRPV4-/- mice at 90/150 mmHg compared to WT. In TRPM8-deficient mice the reduction was only distinct at 150 mmHg. Exposure to selective pharmacological antagonists (HC030031, 100 μM; RN1734, 10 μM; AMTB, 10 μM showed corresponding effects. The unselective TRP blocker ruthenium red (RR, 10 μM was as efficient in inhibiting distension-induced CGRP release as the unselective antagonists of mechanogated DEG/ENaC (amiloride, 100 μM and stretch-activated channels (gadolinium, 50 μM. VMR to CRD revealed prominent deficits over the whole pressure range (up to 90 mmHg in TRPA1-/- and TRPV4-/- but not TRPM8-/- mice; the drug effects of the TRP antagonists were again highly consistent with the results from mice lacking the respective TRP receptor gene.TRPA1 and TRPV4 mediate colonic distension pain and CGRP release and appear to govern a wide and congruent dynamic range of distensions. The role of TRPM8 seems to be confined to signaling extreme noxious distension, at least in the healthy colon.

  11. Regulation of body temperature and nociception induced by non-noxious stress in rat.

    Science.gov (United States)

    Vidal, C; Suaudeau, C; Jacob, J

    1984-04-09

    The effects of 3 different non-noxious stressors on body temperature (Tb) were investigated in the rat: (1) loose restraint in cylinders, (2) removal of the rats from cylinders, exposure to a novel environment and replacement in cylinders, a stressor called here 'novelty', and (3) gentle holding of the rats by the nape of the neck. Loose restraint and 'novelty' produced hyperthermia. On the contrary, holding induced hypothermia. Hypophysectomy (HX) reduced basal Tb, abolished restraint hyperthermia and reduced both 'novelty' hyperthermia and holding hypothermia. Dexamethasone ( DEXA ) had no effect upon either restraint or novelty hyperthermia but reduced the hypothermia. Naloxone (Nx) produced a slight fall in basal Tb accounting for its reduction of restraint and 'novelty' hyperthermias ; it did not affect holding hypothermia. The inhibitory effects of HX suggest a participation of the pituitary in the hyperthermias ; the neurointermediate lobe would be involved as the hyperthermias were not affected by DEXA , which is known to block the stress-induced release of pituitary secretions from the anterior lobe but not from the neurointermediate lobe. In contrast, substances from the anterior lobe might participate in hypothermia due to holding since it is reduced by HX and DEXA . As to the effects of Nx, endogenous opioids would not be significantly involved in the thermic effects of the stressors used in this study; they might play, if any, only a minor role in the regulation of basal Tb. These results are compared with those previously obtained on nociception using the same non-noxious stressors. It emerges that, depending on the stressor, different types of association between thermoregulation and nociception may occur, i.e. hyperthermia with analgesia, hyperthermia with hyperalgesia and hypothermia with hyperalgesia.

  12. Divergent functions of the left and right central amygdala in visceral nociception.

    Science.gov (United States)

    Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

    2017-04-01

    The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

  13. 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

  14. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor. Copyright © 2016. Published by Elsevier Ireland Ltd.

  15. Transcending Transmission

    DEFF Research Database (Denmark)

    Schoeneborn, Dennis; Trittin, Hannah

    2013-01-01

    Purpose – Extant research on corporate social responsibility (CSR) communication primarily relies on a transmission model of communication that treats organizations and communication as distinct phenomena. This approach has been criticized for neglecting the formative role of communication...... in the emergence of organizations. This paper seeks to propose to reconceptualize CSR communication by drawing on the “communication constitutes organizations” (CCO) perspective. Design/methodology/approach – This is a conceptual paper that explores the implications of switching from an instrumental...... to a constitutive notion of communication. Findings – The study brings forth four main findings: from the CCO view, organizations are constituted by several, partly dissonant, and potentially contradictory communicative practices. From that viewpoint, the potential impact of CSR communication becomes a matter...

  16. Recent studies of cutaneous nociception in atopic and non-atopic subjects.

    Science.gov (United States)

    Heyer, G R; Hornstein, O P

    1999-02-01

    Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and

  17. Pre-test habituation improves the reliability of a handheld test of mechanical nociceptive threshold in dairy cows

    DEFF Research Database (Denmark)

    Raundal, P. M.; Andersen, P. H.; Toft, Nils

    2015-01-01

    Mechanical nociceptive threshold (MNT) testing has been used to investigate aspects of painful states in bovine claws. We investigated a handheld tool, where the applied stimulation force was monitored continuously relative to a pre-encoded based target force. The effect on MNT of two pre-testing...... habituation procedures was performed in two different experiments comprising a total of 88 sound Holsteins dairy cows kept either inside or outside their home environment. MNT testing was performed using five consecutive mechanical nociceptive stimulations per cow per test at a fixed pre-encoded target rate...... of 2.1 N/s. The habituation procedure performed in dairy cows kept in their home environment led to lowered intra-individual coefficient of variation of MNT (P test...

  18. Intrathecal administration of clonidine or yohimbine decreases the nociceptive behavior caused by formalin injection in the marsh terrapin (Pelomedusa subrufa)

    DEFF Research Database (Denmark)

    Makau, Christopher M; Towett, Philemon K; Abelson, Klas S P

    2014-01-01

    BACKGROUND: The role of noradrenergic system in the control of nociception is documented in some vertebrate animals. However, there are no data showing the role of this system on nociception in the marsh terrapins. METHODOLOGY: In this study, the antinociceptive action of intrathecal administration...... of the α 2-adrenoreceptor agonist clonidine and α 2-adrenoreceptor antagonist yohimbine was evaluated in the African marsh terrapin using the formalin test. The interaction of clonidine and yohimbine was also evaluated. RESULTS: Intrathecal administration of clonidine (37.5 or 65 μg/kg) caused...... a significant reduction in the mean time spent in pain-related behavior. Yohimbine, at a dose of 25 μg/kg, significantly blocked the effect of clonidine (65 μg/kg). However, administration of yohimbine (40 or 53 μg/kg) caused a significant reduction in the mean time spent in pain-related behavior. Intrathecal...

  19. Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

    International Nuclear Information System (INIS)

    Silva, L.C.R.; Romero, T.R.L.; Guzzo, L.S.; Duarte, I.D.G.

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E 2 (PGE 2 , 2 µg/paw) in the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE 2 , which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 µg/paw) and AM-630 (100 µg/paw) were used as CB 1 and CB 2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 µg dipyrone (mean = 5.825 ± 2.842 g), 20 µg diclofenac (mean = 4.825 ± 3.850 g) and 40 µg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB 1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB 2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac

  20. Objective evaluation for venous leg ulcer-related nociceptive pain using thermography

    Directory of Open Access Journals (Sweden)

    Goto T

    2014-08-01

    Full Text Available Taichi Goto,1 Ayumi Naito,1,2 Nao Tamai,1 Gojiro Nakagami,1 Makoto Mo,3 Hiromi Sanada1 1Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; 2Fujisawa City Hospital, Fujisawa, Kanagawa, Japan; 3Department of Cardiovascular Surgery, Yokohama Minami Kyosai Hospital, Yokohama, Kanagawa, Japan Purpose: We aimed to identify distinguishing characteristics in thermographic images of venous leg ulcer (VLU, for objective evaluation of VLU-related nociceptive pain. Patients and methods: Secondary analysis was performed, using existing data obtained from April to November 2010, for patients with VLU. Thermographic images of wounds and their surrounding area were classified according to the periwound temperature pattern as "normal temperature" or "high temperature". These results were compared with the self-reported pain intensity assessed by the short-form McGill Pain Questionnaire. Cohen's kappa coefficients were used to evaluate the interrater reliability for temperature assessment, and Wilcoxon rank sum test was used to compare pain intensities between the two groups. Results: Among 39 thermographic examinations in eight patients, 22 were classified into the high-temperature group and 17 into the normal-temperature group. Kappa coefficients for the temperature classification were 0.90 between the wound, ostomy, and continence nurse and a wound care specialist, and 0.90 between the wound, ostomy, and continence nurse and a graduate student. The pain rating index (Z=−2.981, P=0.003, sensory pain (Z=−3.083, P=0.002, affective pain (Z=−2.764, P=0.006, and present pain intensity (Z=−2.639, P=0.006 ratings were significantly higher in the high-temperature group than in the normal-temperature group, but the visual analog scale (Z=−0.632, P=0.527 was not significantly different between the two groups. Conclusion: Thermographic pattern may reflect VLU

  1. Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

    Energy Technology Data Exchange (ETDEWEB)

    Silva, L.C.R.; Romero, T.R.L.; Guzzo, L.S.; Duarte, I.D.G. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-09-21

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E{sub 2} (PGE{sub 2}, 2 µg/paw) in the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE{sub 2}, which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 µg/paw) and AM-630 (100 µg/paw) were used as CB{sub 1} and CB{sub 2} cannabinoid receptor antagonists, respectively. Ipl injection of 40 µg dipyrone (mean = 5.825 ± 2.842 g), 20 µg diclofenac (mean = 4.825 ± 3.850 g) and 40 µg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB{sub 1} cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB{sub 2} cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of

  2. Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

    Directory of Open Access Journals (Sweden)

    L.C.R. Silva

    2012-12-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group. Hyperalgesia was induced by a subcutaneous intraplantar (ipl injection of prostaglandin E2 (PGE2, 2 μg/paw in the rat’s hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3 ± 4.505 g. AM-251 (80 μg/paw and AM-630 (100 μg/paw were used as CB1 and CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 μg dipyrone (mean = 5.825 ± 2.842 g, 20 μg diclofenac (mean = 4.825 ± 3.850 g and 40 μg indomethacin (mean = 6.650 ± 3.611 g elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g, diclofenac (mean = 2.50 ± 0.8337 g and indomethacin (mean = 6.650 ± 4.069 g or CB2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g, diclofenac (mean = 6.675 ± 1.368 g and indomethacin (mean = 2.85 ± 5.01 g. Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac and

  3. 17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

    Science.gov (United States)

    Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

    2015-12-01

    Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

  4. [Changes in ingestive behavior during growth affects the functional maturation of temporomandibular joint nociceptive neurons of rats].

    Science.gov (United States)

    Hiranuma, Maya

    2013-03-01

    Temporomandibular joint (TMJ) loading during development promotes its growth and maintains normal structure/function. Continuous change in diet consistency is related to development and maturation of the peripheral nervous system, including the nociceptive system. However, the functional modulation of TMJ-nociceptive neurons under different ingestive behavior is unclear. We fed growing rats a liquid diet to investigate the effects of low TMJ loading on the response properties of neurons in the trigeminal spinal tract subnucleus caudalis (Sp5C). Forty 2-week-old male rats were used. They were fed chow pellets (n = 20, C group) or a liquid diet (n = 20, LD group) soon after weaning. Firing activities of single sensory units in response to TMJ pressure stimuli were recorded at 4, 5, 7 and 9 weeks. In TMJ-nociceptive neurons, the firing threshold (FT) in the LD group was significantly lower than that in the C group at each recording age. The FT in the C group remained unchanged throughout the recording period, whereas that in the LD group was the highest at 4 weeks, and gradually decreased. On the other hand, the initial firing frequency (IFF) was significantly higher in the LD group than in the C group at each recording age. The IFF in the C group remained unchanged throughout the experimental period, whereas that in the LD group was at its lowest at 4 weeks, and gradually increased. Based on these findings, ingestive behavior that results from continuous changes in the physical consistency of the diet during growth may affect the functional maturation of TMJ-nociceptive neurons.

  5. Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception

    OpenAIRE

    Hall, Bradford E.; Prochazkova, Michaela; Sapio, Matthew R.; Minetos, Paul; Kurochkina, Natalya; Binukumar, B. K.; Amin, Niranjana D.; Terse, Anita; Joseph, John; Raithel, Stephen J.; Mannes, Andrew J.; Pant, Harish C.; Chung, Man-Kyo; Iadarola, Michael J.; Kulkarni, Ashok B.

    2018-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and th...

  6. The selective effect of N-feruloylserotonins isolated from Leuzea carthamoides on nociception and anxiety in rats

    Czech Academy of Sciences Publication Activity Database

    Yamamotová, A.; Pometlová, M.; Harmatha, Juraj; Rašková, H.; Rokyta, R.

    2007-01-01

    Roč. 112, č. 2 (2007), s. 368-374 ISSN 0378-8741 R&D Projects: GA MŠk(CZ) 1M0517; GA ČR(CZ) GA203/07/1227 Institutional research plan: CEZ:AV0Z40550506 Keywords : nociception * anxiety * N-feruloylserotonin * Leuzea carthamoides Subject RIV: CC - Organic Chemistry Impact factor: 2.049, year: 2007

  7. Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

    Directory of Open Access Journals (Sweden)

    Yeowool eHuh

    2013-10-01

    Full Text Available Anesthetics are often used to characterize the activity of single neurons in-vivo for its advantages such as reduced noise level and convenience in noxious stimulations. Of the anesthetics, urethane had been widely used in some thalamic studies under the assumption that sensory signals are still relayed to the thalamus under urethane anesthesia and that thalamic response would therefore reflect the response of the awake state. We tested whether this assumption stands by comparing thalamic activity in terms of tonic and burst firing modes during ‘the awake state’ or under ‘urethane anesthesia’ utilizing the extracellular single unit recording technique. First we have tested how thalamic relay neurons respond to the introduction of urethane and then tested how urethane influences thalamic discharges under formalin-induced nociception. Urethane significantly depressed overall firing rates of thalamic relay neurons, which was sustained despite the delayed increase of burst activity over the 4 hour recording period. Thalamic response to nociception under anesthesia was also similar overall except for the slight and transient increase of burst activity. Overall, results demonstrated that urethane suppresses the activity of thalamic relay neurons and that, despite the slight fluctuation of burst firing, formalin-induced nociception cannot significantly change the firing pattern of thalamic relay neurons that was caused by urethane.

  8. Sensitization of the nociceptive system in patients with low back pain and sickness absence: Disc degeneration disease or pain syndrome

    DEFF Research Database (Denmark)

    Jensen, Ole Kudsk; Nielsen, Claus Vinther; Stengaard-Pedersen, Kristian

    SENSITIZATION OF THE NOCICEPTIVE SYSTEM IN PATIENTS WITH LOW BACK PAIN AND SICKNESS ABSENCE O.K. Jensen1, C.V. Nielsen2, K. Stengaard-Pedersen3 1The Spine Center, Department of Internal Medicine, Region Hospital Silkeborg, 2Department of Clinical Social Medicine, University of Aarhus, and 3...... characterized by sensitization of the nociceptive system. Purpose: To assess sensitization of the nociceptive system in low back pain (LBP) patients by means of TP examination and measure of Pressure Pain Threshold (PPT) on the thumb nails. To search for associations between the number of TPs and structural...... = 1.35, p = 0.017) and mental distress (anxiety) in men (OR = 1.39, p = 0.003). After adjustment for age and sex, a positive association between LBP score and DDS was found only in patients with less than six TPs (OR = 1.21 (1.0-1.47), p = 0.043). Low PPT on the thumb nails was associated with DDS...

  9. 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.

  10. Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats.

    Science.gov (United States)

    Lin, Jia-Ji; Du, Yi; Cai, Wen-Ke; Kuang, Rong; Chang, Ting; Zhang, Zhuo; Yang, Yong-Xiang; Sun, Chao; Li, Zhu-Yi; Kuang, Fang

    2015-07-30

    Pain caused by acute pulpitis (AP) is a common symptom in clinical settings. However, its underlying mechanisms have largely remained unknown. Using AP model, we demonstrated that dental injury caused severe pulp inflammation with up-regulated serum IL-1β. Assessment from head-withdrawal reflex thresholds (HWTs) and open-field test demonstrated nociceptive response at 1 day post injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and downstream signaling components of TLR4, including MyD88, TRIF and NF-κB, and cytokines such as TNF-α and IL-1β, were also increased. Retrograde labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp and TLR4 immunoreactivity was mainly in the medium and small neurons. Double labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1 and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4 antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF-κB, TNF-α and IL-1β production and behavior of nociceptive response. Our findings suggest that TLR4 signaling in TG cells, particularly the peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and indicate that TLR4 signaling could be a potential therapeutic target for orofacial pain.

  11. Role of the thalamic parafascicular nucleus cholinergic system in the modulation of acute corneal nociception in rats

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2011-11-01

    Full Text Available The present study investigated the effects of microinjections of acetylcholine (a cholinergic agonist, physostigmine (a cholinesterase inhibitor, atropine (an antagonist of muscarinic cholinergic receptors and hexamethonium (an antagonist of nicotinic cholinergic receptors into the parafascicular nucleus of thalamus on the acute corneal nociception in rats. Acute corneal nociception was induced by putting a drop of 5 M NaCl solution onto the corneal surface of the eye and the number of eye wipes was counted during the first 30s. Both acetylcholine and physostigmine at the same doses of 0.5, 1 and 2 μg significantly (P < 0.05 reduced the number of eye wipes. The intensity of corneal nociception was not changed when atropine and hexamethonium were used alone. Atropine (4 μg, but not hexamethonium (4 μg significantly (P < 0.05 prevented acetylcholine (2 μg- and physostigmine (2 μg-induced antinociceptive effects. The results indicated that at the level of the parafascicular nucleus of thalamus, the muscarinic cholinergic receptors might be involved in the antinociceptive effects of acetylcholine and physostigmine.

  12. microRNAs in nociceptive circuits as predictors of future clinical applications

    Directory of Open Access Journals (Sweden)

    Michaela eKress

    2013-10-01

    Full Text Available Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs (ncRNAs – and microRNAs (miRNAs in particular - regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesised as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioural components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome (CRPS. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.

  13. Tramadol effects on clinical variables and the mechanical nociceptive threshold in horses

    Directory of Open Access Journals (Sweden)

    Leandro Guimarães Franco

    2014-03-01

    Full Text Available This study assessed the clinical effects and the mechanical antinociceptive potential of intravenous (IV tramadol in horses.A blinded and randomized study was designed with 7 horses treated with 1 (Tr1, 2 (Tr2 or 3 (Tr3 mg kg-1 of tramadol IV. The heart rate, respiratory rate (fR, arterial pressure, degree of sedation, gastrointestinal motility (GI, behavior changes and the mechanical nociceptive threshold (MNT were evaluated. The MNT was determined with von Frey device method.Tr3 had a significant increase in their fR and more pronounced behavioral changes than other treatments.The Tr1 showed a significant increase in arterial pressure. The GI reduced significantly, mainly in Tr2. The tramadol did not change the MNT of the horses.The clinical alterations observed with the different treatments were considered mild and transitory, being most evident in Tr2. However the tramadol did not have any analgesic effect with any of the doses evaluated.

  14. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-03-05

    ..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.

  15. Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron.

    Science.gov (United States)

    O'Brien, Barbara M J; Palumbos, Sierra D; Novakovic, Michaela; Shang, Xueying; Sundararajan, Lakshmi; Miller, David M

    2017-12-15

    The dendritic processes of nociceptive neurons transduce external signals into neurochemical cues that alert the organism to potentially damaging stimuli. The receptive field for each sensory neuron is defined by its dendritic arbor, but the mechanisms that shape dendritic architecture are incompletely understood. Using the model nociceptor, the PVD neuron in C. elegans, we determined that two types of PVD lateral branches project along the dorsal/ventral axis to generate the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and (2) Commissural dendrites that fasciculate with circumferential motor neuron processes. Previous reports have shown that the LIM homeodomain transcription factor MEC-3 is required for all higher order PVD branching and that one of its targets, the claudin-like membrane protein HPO-30, preferentially promotes outgrowth of pioneer branches. Here, we show that another MEC-3 target, the conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the alternative role of specifying commissural dendrites. The known EGL-46 binding partner, the TEAD transcription factor EGL-44, is also required for PVD commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong enhancement of the lateral branching defect with decreased numbers of both pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44 function downstream of MEC-3 and in parallel acting pathways to direct outgrowth of two distinct classes of PVD dendritic branches. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Mechanical nociception thresholds in lame sows: evidence of hyperalgesia as measured by two different methods.

    Science.gov (United States)

    Nalon, E; Maes, D; Piepers, S; van Riet, M M J; Janssens, G P J; Millet, S; Tuyttens, F A M

    2013-11-01

    Lameness is a frequently occurring, painful condition of breeding sows that may result in hyperalgesia, i.e., an increased sensitivity to pain. In this study a mechanical nociception threshold (MT) test was used (1) to determine if hyperalgesia occurs in sows with naturally-occurring lameness; (2) to compare measurements obtained with a hand-held probe and a limb-mounted actuator connected to a digital algometer; and (3) to investigate the systematic left-to-right and cranial-to-caudal differences in MT. Twenty-eight pregnant sows were investigated, of which 14 were moderately lame and 14 were not lame. Over three testing sessions, repeated measurements were taken at 5 min intervals on the dorsal aspects of the metatarsi and metacarpi of all limbs. The MT was defined as the force in Newtons (N) that elicited an avoidance response, and this parameter was found to be lower in limbs affected by lameness than in normal limbs (Ptesting sessions (P<0.001), as well as between days (P<0.001). The findings provide evidence that lame sows experience hyperalgesia. Systematic differences between forelimb and hindlimb MT must be taken into account when such assessments are performed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    International Nuclear Information System (INIS)

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-01-01

    β-endorphin, [met]enkephalin, and [leu]enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO 4 or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. β-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; [met]enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; [leu]-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs

  18. Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms

    Science.gov (United States)

    Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J.; Gupta, Kalpna

    2016-01-01

    Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints. PMID:27687125

  19. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Directory of Open Access Journals (Sweden)

    Liu Xian-Guo

    2011-03-01

    Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  20. Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life

    Science.gov (United States)

    Li, Jie; Blankenship, Meredith L.; Baccei, Mark L.

    2013-01-01

    Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst-firing and are distinguished by a lower “leak” membrane conductance compared to adjacent, non-bursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (Kir) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and non-pacemakers indicate the presence of functionally distinct Kir currents in these two populations at room temperature. However, Kir currents in both groups showed high sensitivity to block by extracellular Ba2+ (IC50 ~ 10 µM), which suggests the presence of ‘classical’ Kir (Kir2.x) channels in the neonatal SDH. The reduced Kir conductance within pacemakers is unlikely to be explained by an absence of particular Kir2.x isoforms, as immunohistochemical analysis revealed the expression of Kir2.1, Kir2.2 and Kir2.3 within spontaneously bursting neurons. Importantly, Ba2+ application unmasked rhythmic burst-firing in ~42% of non-bursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst-firing within lamina I was enhanced in the presence of high internal concentrations of free Mg2+, consistent with its documented ability to block Kir channels from the intracellular side. Collectively, the results indicate that Kir channels are key modulators of pacemaker activity in newborn central pain networks. PMID:23426663

  1. Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

    Science.gov (United States)

    Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

    2005-01-01

    As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects.

  2. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    Directory of Open Access Journals (Sweden)

    Heike L Rittner

    2009-04-01

    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  3. Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients.

    Science.gov (United States)

    Biurrun Manresa, José A; Sörensen, Jan; Andersen, Ole K; Arendt-Nielsen, Lars; Gerdle, Björn

    2015-12-01

    Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

  4. Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.

    Science.gov (United States)

    Liang, M; Lee, M C; O'Neill, J; Dickenson, A H; Iannetti, G D

    2016-08-01

    Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. Copyright © 2016 the American Physiological Society.

  5. Role of olfactory reactions, nociception, and immunoendocrine shifts in addictive disorders.

    Science.gov (United States)

    Masterova, Elena; Nevidimova, Tatiana; Savochkina, Dariya; Nikitina, Valentina; Lobacheva, Olga; Vetlugina, Tamara; Bokhan, Nikolay

    2017-09-01

    Addictive pathology is associated with nervous, immune, and endocrine shifts. Meanwhile, the nature of intersystemic relationship lying beneath addictive disorders remains unclear. The purpose of the study was to identify neuroimmunoendocrine markers of addictive disorders in male subjects defining the nature of their interaction. The study enrolled 69 subjects aged 18-43 years: 59 males and 10 females divided into those with addictive disorders (n = 39) and conditionally healthy subjects (n = 30). EEG testing with olfactory stimulation, olfactometric, and pressure algometric examinations was carried out. Multiplex technique was applied to determine mitogen-induced production of cytokines IL-10, IL-1, IL-1RA, IL-2, IFN-gamma, TNF-alpha. ELISA method was applied to measure serum cortisol and testosterone levels. Olfactory responses to isopropanol with open eyes in addicted patients manifested as increase in alpha-rhythm and beta1-rhythm, with closed eyes presentation of this odorant was accompanied by increase of theta-rhythm in opioid-addicted patients. Male subjects with addictive disorders showed reduced alpha-rhythm in terms of olfactory stimulation with modified emotional evaluation of the odorant, deficient mitogen-induced production of IFN-gamma, and reduced pain sensitivity. Male subjects with opioid addiction had reduced beta1-rhythm in terms of olfactory stimulation, mitogen-induced production of IFN-gamma, and elevated testosterone level. The findings obtained verify potential involvement of nociception, olfaction, and cytokine production in addiction pathogenesis evidencing their various roles depending on the range of psychoactive substances (PAS) and pathology progression. The data obtained may provide background for unification of reward circuit and inhibitory control concepts in regulation of addictive behavior. (Am J Addict 2017;26:640-648). © 2017 American Academy of Addiction Psychiatry.

  6. Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

    Directory of Open Access Journals (Sweden)

    L Xiao

    2017-09-01

    Full Text Available Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT and extracellular signal regulated kinase (ERK pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (μCT data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a

  7. Survey of Transmission Cost Allocation Methodologies for Regional Transmission Organizations

    Energy Technology Data Exchange (ETDEWEB)

    Fink, S.; Porter, K.; Mudd, C.; Rogers, J.

    2011-02-01

    The report presents transmission cost allocation methodologies for reliability transmission projects, generation interconnection, and economic transmission projects for all Regional Transmission Organizations.

  8. Anti-nociceptive and anti-hyperprolactinemia activities of Fructus Viticis and its effective fractions and chemical constituents.

    Science.gov (United States)

    Hu, Y; Xin, H-L; Zhang, Q-Y; Zheng, H-C; Rahman, K; Qin, L-P

    2007-10-01

    Vitex rotundifolia L. is widely distributed along the sea coast of China. The aim of this study was to investigate the anti-nociceptive and anti-hyperprolactinemia activities of substances isolated from Fructus Viticis (the fruit of Vitex rotundifolia), which may be effective in the treatment of pre-menstrual symptoms, using acetic-acid-induced writhing and metoclopramide-dihydrochloride-induced hyperprolactinemia in mice. The fractions effective in terms of anti-nociceptive and anti-hyperprolactinemia activities were obtained from Fructus Viticis by elution through macro-porous resin, and polyamide and silica gel column chromatography. The standardization of the fractions obtained from the separation procedures was carried out by means of high-performance liquid chromatography (HPLC)-fingerprint. In this study, the flavone-enriched fraction (Fraction 6) showed a higher inhibitory rate than indomethacin (69.4% vs. 56.4%) at a dose of 50 mg/kg body wt., and significantly reduced the prolactin level as compared to HPRL-treated mice (8.2 ng/ml vs. 25.5 ng/ml). Furthermore, this fraction showed anti-nociceptive activity in a dose-dependent manner (10-50 mg/kg body wt., i.g.). On further purification with silica gel, Casticin was isolated from this fraction and it decreased abnormal serum levels of prolactin by approximately 50% (p screening methods, our results indicate that the presence of flavonoids such as Casticin in this plant may be responsible for the activity effects. Casticin has potent analgesic and anti-hyperprolactinaemia properties, is likely to be one of the active components of Fructus Viticis, and may have a role in treating PMS (premenstrual syndrom).

  9. Thermal nociception as a measure of non-steroidal anti-inflammatory drug effectiveness in broiler chickens with articular pain☆

    Science.gov (United States)

    Caplen, Gina; Baker, Laurence; Hothersall, Becky; McKeegan, Dorothy E.F.; Sandilands, Victoria; Sparks, Nick H.C.; Waterman-Pearson, Avril E.; Murrell, Joanna C.

    2013-01-01

    Pain associated with poultry lameness is poorly understood. The anti-nociceptive properties of two non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated using threshold testing in combination with an acute inflammatory arthropathy model. Broilers were tested in six groups (n = 8 per group). Each group underwent a treatment (saline, meloxicam (3 or 5 mg/kg) or carprofen (15 or 25 mg/kg)) and a procedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to testing. Induced groups had Freund’s complete adjuvant injected intra-articularly into the left intertarsal joint (hock). A ramped thermal stimulus (1 °C/s) was applied to the skin of the left metatarsal. Data were analysed using random-intercept multi-level models. Saline-induced birds had a significantly higher skin temperature (± SD) than saline-sham birds (37.6 ± 0.8 °C vs. 36.5 ± 0.5 °C; Z = −3.47, P carprofen: Z = 2.58, P = 0.010) in induced birds. Saline-induced birds also had significantly lower TT than saline-sham birds (Z = −2.17, P = 0.030). This study found direct evidence of an association between inflammatory arthropathies and thermal hyperalgesia, and showed that NSAID treatment maintained baseline thermal sensitivity (via anti-nociception). Quantification of nociceptive responsiveness in a predictable broiler pain model identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested that therapeutically effective treatment was provided at the doses administered. Such validation of analgesic strategies will increase the understanding of pain associated with specific natural broiler lameness types. PMID:24129110

  10. Steady-state evoked potentials to study the processing of tactile and nociceptive somatosensory input in the human brain.

    Science.gov (United States)

    Colon, E; Legrain, V; Mouraux, A

    2012-10-01

    The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response of corresponding frequency, known as steady-state evoked potentials (SS-EP). In visual, auditory and vibrotactile modalities, studies have shown that SS-EP reflect mainly activity originating from early, modality-specific sensory cortices. Furthermore, it has been shown that SS-EP have several advantages over the recording of transient event-related brain potentials (ERP), such as a high signal-to-noise ratio, a shorter time to obtain reliable signals, and the capacity to frequency-tag the cortical activity elicited by concurrently presented sensory stimuli. Recently, we showed that SS-EP can be elicited by the selective activation of skin nociceptors and that nociceptive SS-EP reflect the activity of a population of neurons that is spatially distinct from the somatotopically-organized population of neurons underlying vibrotactile SS-EP. Hence, the recording of SS-EP offers a unique opportunity to study the cortical representation of nociception and touch in humans, and to explore their potential crossmodal interactions. Here, (1) we review available methods to achieve the rapid periodic stimulation of somatosensory afferents required to elicit SS-EP, (2) review previous studies that have characterized vibrotactile and nociceptive SS-EP, (3) discuss the nature of the recorded signals and their relationship with transient event-related potentials and (4) outline future perspectives and potential clinical applications of this technique. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-02-01

    OBJECTIVES: Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (+\\/- leg) pain disorders. METHODS: This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (+\\/- leg) pain were assessed using a standardized assessment protocol. After each assessment, patients\\' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various clinical criteria. RESULTS: Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive\\/negative predictive values, positive\\/negative likelihood ratios). DISCUSSION: By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  12. Ethanolic extract of Aconiti Brachypodi Radix attenuates nociceptive pain probably via inhibition of voltage-dependent Na⁺ channel.

    Science.gov (United States)

    Ren, Wei; Yuan, Lin; Li, Jun; Huang, Xian-Ju; Chen, Su; Zou, Da-Jiang; Liu, Xiangming; Yang, Xin-Zhou

    2012-01-01

    Aconiti Brachypodi Radix, belonging to the genus of Aconitum (Family Ranunculaceae), are used clinically as anti-rheumatic, anti-inflammatory and anti-nociceptive in traditional medicine of China. However, its mechanism and influence on nociceptive threshold are unknown and need further investigation. The analgesic effects of ethanolic extract of Aconiti Brachypodi Radix (EABR) were thus studied in vivo and in vitro. Three pain models in mice were used to assess the effect of EABR on nociceptive threshold. In vitro study was conducted to clarify the modulation of the extract on the tetrodotoxin-sensitive (TTX-S) sodium currents in rat's dorsal root ganglion (DRG) neurons using whole-cell patch clamp technique. The results showed that EABR (5-20 mg/kg, i.g.) could produce dose-dependent analgesic effect on hot-plate tests as well as writhing response induced by acetic acid. In addition, administration of 2.5-10 mg/kg EABR (i.g.) caused significant decrease in pain responses in the first and second phases of formalin test without altering the PGE₂ production in the hind paw of the mice. Moreover, EABR (10 µg/ml -1 mg/ml) could suppress TTX-S voltage-gated sodium currents in a dose-dependent way, indicating the underlying electrophysiological mechanism of the analgesic effect of the folk plant medicine. Collectively, our results indicated that EABR has analgesic property in three pain models and useful influence on TTX-S sodium currents in DRG neurons, suggesting that the interference with pain messages caused by the modulation of EABR on TTX-S sodium currents in DRG neurones may explain some of its analgesic effect.

  13. Determination of the temperature causing a nociceptive response in the tail of albino BALB/c mice.

    Science.gov (United States)

    Aguirre Siancas, E E; Lam Figueroa, N M; Delgado Rios, J C; Ruiz Ramirez, E; Portilla Flores, O S; Crispín Huamaní, L J; Alarcón Velásquez, L

    2018-06-08

    Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful. Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13 cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water. Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123). The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Anti-nociceptive and anti-inflammatory activities of ethanolic flower extract of Newbouldia laevis in mice and rats

    OpenAIRE

    Y Tanko; B Kamba; MI Saleh; K Y Musa; A Mohammed

    2008-01-01

    Summary: The ethanolic flower extract of Newbouldia laevis was investigated for possible anti-nociceptive and anti-inflammatory effects in rodents. Acetic acid induced writhing (in mice) and formalin tests (in rats) were used to study. The extract caused a significant decrease (P< 0.05), which was not dose a dependent inhibition on acetic acid-induced writhing and the neurogenic pain induced by formalin. The extract at the doses (25, 50 and 100mg/kg) tested showed 59, 71 and 47% inhibition...

  15. Influence of dental correction on nociceptive test responses, fecal appearance, body condition score, and apparent digestibility coefficient for dry matter of Zamorano-leones donkeys (Equus asinus).

    Science.gov (United States)

    Rodrigues, J B; Ferreira, L M; Bastos, E; San Roman, F; Viegas, C; Santos, A S

    2013-10-01

    The influence of dental correction on nociceptive (pressure) test responses, fecal appearance, BCS, and apparent digestibility coefficient for DM was studied in 18 Zamorano-Leonés donkeys, an endangered local breed from the Zamora province in Spain. For this purpose, donkeys were divided into 2 homogeneous control and treatment groups, based on age, BCS, and dental findings. On d 1, 45, 90, and 135, BCS and nociceptive test responses were evaluated in all donkeys. Feed and fecal samples were collected from all donkeys for 3 consecutive days, starting at each of the aforementioned days. Apparent digestibility coefficient for DM was estimated, using ADL as an internal marker. A progressive decrease of positive nociceptive test responses was observed from d 1 up to 90 (P donkeys but also the equid population, in general, to improve their welfare.

  16. Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle.

    Science.gov (United States)

    Dideriksen, Jakob L; Holobar, Ales; Falla, Deborah

    2016-08-01

    Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle. Copyright © 2016 the American Physiological Society.

  17. Anti-nociceptive effect of patchouli alcohol: Involving attenuation of cyclooxygenase 2 and modulation of mu-opioid receptor.

    Science.gov (United States)

    Yu, Xuan; Wang, Xin-Pei; Yan, Xiao-Jin; Jiang, Jing-Fei; Lei, Fan; Xing, Dong-Ming; Guo, Yue-Ying; Du, Li-Jun

    2017-08-09

    To explore the anti-nociceptive effect of patchouli alcohol (PA), the essential oil isolated from Pogostemon cablin (Blanco) Bent, and determine the mechanism in molecular levels. The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to confifirm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor (MOR). Cyclooxygenase 2 (COX2) and MOR of mouse brain were expressed for determination of PA's target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution (Peffect of PA. A decrease in the intracellular calcium level (Peffect. PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Both COX2 and MOR are involved in the mechanism of PA's anti-nociceptive effect, and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA's effect on MOR.

  18. Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat.

    Science.gov (United States)

    Li, Ai-Ling; Sibi, Jiny E; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo

    2016-06-01

    Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas.

  19. Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis.

    Science.gov (United States)

    Conte, Antonella; Bettolo, Chiara Marini; Onesti, Emanuela; Frasca, Vittorio; Iacovelli, Elisa; Gilio, Francesca; Giacomelli, Elena; Gabriele, Maria; Aragona, Massimiliano; Tomassini, Valentina; Pantano, Patrizia; Pozzilli, Carlo; Inghilleri, Maurizio

    2009-05-01

    Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.

  20. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  1. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

    Science.gov (United States)

    Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

  2. Automated single-trial assessment of laser-evoked potentials as an objective functional diagnostic tool for the nociceptive system.

    Science.gov (United States)

    Hatem, S M; Hu, L; Ragé, M; Gierasimowicz, A; Plaghki, L; Bouhassira, D; Attal, N; Iannetti, G D; Mouraux, A

    2012-12-01

    To assess the clinical usefulness of an automated analysis of event-related potentials (ERPs). Nociceptive laser-evoked potentials (LEPs) and non-nociceptive somatosensory electrically-evoked potentials (SEPs) were recorded in 37 patients with syringomyelia and 21 controls. LEP and SEP peak amplitudes and latencies were estimated using a single-trial automated approach based on time-frequency wavelet filtering and multiple linear regression, as well as a conventional approach based on visual inspection. The amplitudes and latencies of normal and abnormal LEP and SEP peaks were identified reliably using both approaches, with similar sensitivity and specificity. Because the automated approach provided an unbiased solution to account for average waveforms where no ERP could be identified visually, it revealed significant differences between patients and controls that were not revealed using the visual approach. The automated analysis of ERPs characterized reliably and objectively LEP and SEP waveforms in patients. The automated single-trial analysis can be used to characterize normal and abnormal ERPs with a similar sensitivity and specificity as visual inspection. While this does not justify its use in a routine clinical setting, the technique could be useful to avoid observer-dependent biases in clinical research. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Differences in neurotransmitter systems of ventrolateral periaqueductal gray between the micturition reflex and nociceptive regulation: An in vivo microdialysis study.

    Science.gov (United States)

    Kitta, Takeya; Mitsui, Takahiko; Kanno, Yukiko; Chiba, Hiroki; Moriya, Kimihiko; Yoshioka, Mitsuhiro; Shinohara, Nobuo

    2016-07-01

    To elucidate the possible involvement of glutamate and serotonin (5-hydroxytryptamine) neurons in the ventrolateral midbrain periaqueductal gray during noxious stimulation. The study was carried out by evoking a noxious stimulation by acetic acid in an animal model of cystitis. Changes in glutamate and 5-hydroxytryptamine in the periaqueductal gray during the micturition reflex and acetic acid-induced cystitis were determined using in vivo microdialysis combined with cystometry in rats. Extracellular glutamate levels slightly, but significantly, increased during the micturition reflex induced by saline infusion into the bladder. Intravesical infusion of acetic acid facilitated the micturition reflex characterized by increases in voiding pressure and decreases in the intercontraction interval. Glutamate levels were markedly increased by acetic acid, and this enhancement was sustained for at least 3 h. 5-Hydroxytryptamine levels, which were not altered during the micturition reflex, were increased after intravesical infusion of acetic acid. The results suggest that periaqueductal gray glutamate and 5-hydroxytryptamine neurons differentially participate in the modulation of both nociception and the micturition reflex. Furthermore, periaqueductal gray 5-hydroxytryptamine levels appear to reflect the nociceptive stimuli. © 2016 The Japanese Urological Association.

  4. D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice

    Directory of Open Access Journals (Sweden)

    Serena Boccella

    2015-01-01

    Full Text Available D-Aspartate (D-Asp is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO. D-Asp acts as an agonist on NMDA receptors (NMDARs. Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo−/− or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo−/− mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo−/− mice show an increased evoked activity of the nociceptive specific (NS neurons of the dorsal horn of the spinal cord (L4–L6 and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.

  5. Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

    Science.gov (United States)

    Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

    2018-05-01

    The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

  6. Space power transmission

    Energy Technology Data Exchange (ETDEWEB)

    Kuribayashi, Shizuma [Mitsubishi Heavy Industries, Ltd., Tokyo, (Japan)

    1989-10-05

    There being a conception to utilize solar energy by use of a space power station (SPS), a method to bring that universal grace to mankind is wireless energy transmission. The wireless energy transmission is regarded to be microwave transmission or laser beam transmission. The microwave transmission is to transmit 2.45GHz band microwave from the SPS to a receiving station on the ground to meet power demand on earth. The microwave, as small in attenuation in atmosphere and resistant against rain and cloud, is made candidate and, however, problematic in influence on organism, necessary large area of receiving antenna and many other points to be studied. While the laser transmission, as more convergent of beam than the microwave transmission, is advantageous with enabling the receiving area to be small and, however, disadvantageous with being not resistant against dust, rain and cloud, if used for the energy transmission between the space and earth. 2 refs., 2 figs.

  7. Transmission on Balance 2006

    International Nuclear Information System (INIS)

    2007-02-01

    Every year he Dutch Transmission System Operator (TSO) TenneT issues the title publication 'Transmission on Balance'. This report provides information about the main technical operating results in the past year.

  8. Tachycardia in response to remote capsaicin injection as a model for nociception in the ball python (Python regius).

    Science.gov (United States)

    Williams, Catherine J A; James, Lauren E; Bertelsen, Mads F; Wang, Tobias

    2016-07-01

    To quantify the effect of subcutaneous (SC) capsaicin injection on heart rate (HR) in ball pythons (Python regius) and to assess the efficacy of two opioids (morphine and butorphanol) in modifying this response. Prospective, randomized, unmatched study. Eleven mixed-sex, captive-bred ball pythons. Snakes were randomly assigned to three groups (n = 6) by intramuscular premedication: 1) control: saline (0.9 mL); 2) morphine (10 mg kg(-1) ); and 3) butorphanol (10 mg kg(-1) ). Three snakes were tested twice and another two were tested three times in different treatments administered 1 month apart. Under isoflurane anaesthesia, snakes were instrumented with SC electrocardiogram (ECG) electrodes and an SC catheter for remote stimulus delivery. After recovery from anaesthesia, all snakes, in visual and audial isolation from the experimenter, received a sham stimulus of saline (0.4 mL) via the SC catheter. A nociceptive stimulus of SC capsaicin (3 mg in 0.2 mL saline with 7% Tween 80) was then applied by catheter at 7 hours after premedication. In a subset (n = 3), two sham injections (saline 0.2 mL) preceded the capsaicin treatment. HR was recorded via ECG, and changes in HR (ΔHR) from baseline were calculated for all stimulations. Capsaicin injection was associated with a significant increase in HR [peak ΔHR: saline group: 8.8 ± 7.1 beats minute(-1) ; capsaicin group: 21.1 ± 5.8 beats minute(-1) (p = 0.0055)] and integrated ΔHR as a function of time. The administration of morphine or butorphanol 7 hours prior to nociception failed to significantly reduce the peak and integrated ΔHR. Butorphanol caused marked, long-lasting sedation as assessed by muscle tone. The HR response to an SC capsaicin injection can serve as a nociceptive model in P. regius. Morphine and butorphanol administration did not reduce HR response to capsaicin stimulation but produced significantly different effects on pre-stimulation HR and sedation. © 2015 Association

  9. The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

    Directory of Open Access Journals (Sweden)

    Li Li

    2014-01-01

    Full Text Available The present study examined nociceptive behaviors and the expression of phosphorylated cAMP response element-binding protein (pCREB in the dorsal horn of the lumbar spinal cord and the dorsal root ganglion (DRG evoked by bee venom (BV. The effect of intraplantar preapplication of the somatostatin analog octreotide on nociceptive behaviors and pCREB expression was also examined. Subcutaneous injection of BV into the rat unilateral hindpaw pad induced significant spontaneous nociceptive behaviors, primary mechanical allodynia, primary thermal hyperalgesia, and mirror-thermal hyperalgesia, as well as an increase in pCREB expression in the lumbar spinal dorsal horn and DRG. Octreotide pretreatment significantly attenuated the BV-induced lifting/licking response and mechanical allodynia. Local injection of octreotide also significantly reduced pCREB expression in the lumbar spinal dorsal horn and DRG. Furthermore, pretreatment with cyclosomatostatin, a somatostatin receptor antagonist, reversed the octreotide-induced inhibition of the lifting/licking response, mechanical allodynia, and the expression of pCREB. These results suggest that BV can induce nociceptive responses and somatostatin receptors are involved in mediating the antinociception, which provides new evidence for peripheral analgesic action of somatostatin in an inflammatory pain state.

  10. [THE CHANGES OF NOCICEPTIVE THRESHOLD AND ACTIVITY OF THE ADENYLYL CYCLASE SYSTEM IN THE SKELETAL MUSCLES OF RATS WITH ACUTE AND MILD TYPE 1 DIABETES MELLITUS ].

    Science.gov (United States)

    Shipilov, V N; Trost, A M; Chistyakova, O V; Derkach, K V; Shpakov, A O

    2016-02-01

    Diabetic peripheral neuropathy (DPN) is one of the most common complications of the type 1 diabetes mellitus (DM1). The aim of the work was to study the dynamics of a painful DPN and functional state of the hormone-sensitive ACSS in the skeletal muscles of rats with the models of acute and mild DM1, as well as the study of impact on them of insulin therapy with different ways of hormone delivery - intranasal and peripheral. In both models of DM1, the level of nociceptive threshold in rats decreased and the stimulatory effects of guanine nucleotides (GppNHp) and adrenergic agonists (isoproterenol, BRL-37344) on adenylyl cyclase (AC) activity were attenuated. The AC stimulating effect of relaxin decreased in animals with acute DM1, but in mild DM1, the decrease was insignificant. Peripheral administration of insulin in rats with acute DM1 increased the nociceptive threshold and partially restored the AC effect of ß 3-agonist BRL-37344. Intranasal administration of insulin in rats with DM1 also increased the nociceptive threshold and partially restored the basal and BRL-37344-stimulated AC activity in the skeletal muscles of diabetic animals. Thus, in the skeletal muscles of rats with acute and mild DM1 the nociceptive sensitivity and the functions of ACSS were disturbed, and they were partially restored by the treatment with peripheral (acute DM1) or intranasal (mild DM1) insulin.

  11. Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe magnus of rats: an effect attenuated by naloxone.

    Science.gov (United States)

    Huang, Y; Brodda-Jansen, G; Lundeberg, T; Yu, L C

    2000-08-04

    The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.

  12. Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

    Directory of Open Access Journals (Sweden)

    Eiji Masaki

    2016-03-01

    Full Text Available Background: Brain-derived neurotrophic factor (BDNF from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. Results: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. Conclusion: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.

  13. Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation

    NARCIS (Netherlands)

    Hoskin, KL; Bulmer, DCE; Lasalandra, M; Jonkman, A; Goadsby, PJ

    There is an accumulating body of evidence suggesting that the periaqueductal grey (PAG) is involved in the pathophysiology of migraine. Positron emission tomography (PET) studies in humans have shown that the caudal ventrolateral midbrain, encompassing the ventrolateral PAG, has activations during

  14. The automotive transmission book

    CERN Document Server

    Fischer, Robert; Jürgens, Gunter; Najork, Rolf; Pollak, Burkhard

    2015-01-01

    This book presents essential information on systems and interactions in automotive transmission technology and outlines the methodologies used to analyze and develop transmission concepts and designs. Functions of and interactions between components and subassemblies of transmissions are introduced, providing a basis for designing transmission systems and for determining their potentials and properties in vehicle-specific applications: passenger cars, trucks, buses, tractors, and motorcycles. With these fundamentals the presentation provides universal resources for both state-of-the-art and future transmission technologies, including systems for electric and hybrid electric vehicles.

  15. Delayed onset of changes in soma action potential genesis in nociceptive A-beta DRG neurons in vivo in a rat model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Henry James L

    2009-09-01

    Full Text Available Abstract Background Clinical data on osteoarthritis (OA suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this model, the present electrophysiological study compared properties of primary sensory nociceptive neurons at one and two months after model induction with properties in naïve control animals. Pilot data indicated no difference in C- or Aδ-fiber associated neurons and therefore the focus is on Aβ-fiber nociceptive neurons. Results At one month after unilateral derangement of the knee by cutting the anterior cruciate ligament and removing the medial meniscus, the only changes observed in Aβ-fiber dorsal root ganglion (DRG neurons were in nociceptor-like unresponsive neurons bearing a hump on the repolarization phase; these changes consisted of longer half width, reflecting slowed dynamics of AP genesis, a depolarized Vm and an increased AP amplitude. At two months, changes observed were in Aβ-fiber high threshold mechanoreceptors, which exhibited shorter AP duration at base and half width, shorter rise time and fall time, and faster maximum rising rate/maximum falling rate, reflecting accelerated dynamics of AP genesis. Conclusion These data indicate that Aβ nociceptive neurons undergo significant changes that vary in time and occur later than changes in structure and in nociceptive scores in this surgically induced OA model. Thus, if changes in Aβ-fiber nociceptive neurons in this model reflect a role in OA pain, they may relate to mechanisms underlying pain associated with advanced OA.

  16. Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models.

    Science.gov (United States)

    Boakye-Gyasi, Eric; Henneh, Isaac Tabiri; Abotsi, Wonder Kofi Mensah; Ameyaw, Elvis Ofori; Woode, Eric

    2017-04-26

    Despite substantial advances in pain research and treatment, millions of people continue to suffer from pain and this has been attributed mainly to the unavailability of effective and safer analgesics. The use of plants as medicines is still widespread and plants constitute a large source of novel phytocompounds that might become leads for the discovery of newer, effective and safer alternatives. Various parts of Ziziphus abyssinica have been used in folk medicine in several African countries as painkillers. However, there is no report on the possible anti-nociceptive effects of this plant especially the leaves, hence the need for this current study. The possible anti-nociceptive activity of hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) was assessed in rodents using chemical (acetic acid, formalin and glutamate), thermal (tail-immersion test) and mechanical/inflammatory (carrageenan) models of nociception. EthE (30-300 mg/kg, p.o.) dose-dependently and significantly inhibited chemical-induced nociception with a maximum inhibition of 86.29 ± 2.27%, 76.34 ± 5.67%, 84.97 ± 5.35%, and 82.81 ± 5.97% respectively for acetic acid, formalin (phase 1), formalin (phase 2) and glutamate tests at its highest dose. EthE also dose-dependently and significantly increased reaction times in both tail-immersion and carrageenan-induced hypernociceptive tests. The activities of the extract in the various models were comparable with the effect of morphine hydrochloride and diclofenac sodium used as standard analgesic drugs. Oral administration of hydro-ethanolic leaf extract of Ziziphus abyssinica ameliorates nocifensive behaviours associated with chemical-, thermal- and mechanical/inflammatory - induced nociceptive pain.

  17. Pressure pain threshold changes after repeated mechano-nociceptive stimulation of the trapezius muscle: possible influence of previous pain experience

    DEFF Research Database (Denmark)

    Sjölund, Bengt H; Persson, Ann L

    2007-01-01

    or an increase. Normalized data, transformed into mean unidirectional PPT differences, showed statistically highly significant changes after intervention. The relative risk of reacting with lowered PPTs on noxious stimulation was 3.7 times higher for subjects who had not given birth to children than for subjects...... over 1 trapezius muscle (skin anaesthetized) in 27 healthy women before and after the intervention. With a mean stimulation rate of 0.40 Hz and a mean nociceptive stimulation intensity of 1.78 x Threshold, subjects were found to systematically react with a change in PPT, either a decrease...... who had given birth to 1 or several children (Pstimulation of the trapezius muscle in healthy females evokes moderate and temporary...

  18. Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

    Science.gov (United States)

    Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

    2016-01-01

    Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

  19. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception

    Directory of Open Access Journals (Sweden)

    Giuseppe Mancuso

    2015-10-01

    Full Text Available Ruta graveolens (rue is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  20. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.

    Science.gov (United States)

    Mancuso, Giuseppe; Borgonovo, Gigliola; Scaglioni, Leonardo; Bassoli, Angela

    2015-10-16

    Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  1. Evidence for spinal N-methyl-d-aspartate receptor involvement in prolonged chemical nociception in the rat.

    Science.gov (United States)

    Haley, Jane E; Dickenson, Anthony H

    2016-08-15

    We used in vivo electrophysiology and a model of more persistent nociceptive inputs to monitor spinal cord neuronal activity in anaesthetised rats to reveal the pharmacology of enhanced pain signalling. The study showed that all responses were blocked by non-selective antagonism of glutamate receptors but a selective and preferential role of the N-methyl-d-aspartate (NMDA) receptor in the prolonged plastic responses was clearly seen. The work lead to many publications, initially preclinical but increasingly from patient studies, showing the importance of the NMDA receptor in central sensitisation within the spinal cord and how this could relate to persistent pain states. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

    Science.gov (United States)

    Tokusumi, Yumiko; Tokusumi, Tsuyoshi; Schulz, Robert A

    2017-05-13

    In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge. Copyright © 2017. Published by Elsevier Inc.

  3. Pellicle transmission uniformity requirements

    Science.gov (United States)

    Brown, Thomas L.; Ito, Kunihiro

    1998-12-01

    Controlling critical dimensions of devices is a constant battle for the photolithography engineer. Current DUV lithographic process exposure latitude is typically 12 to 15% of the total dose. A third of this exposure latitude budget may be used up by a variable related to masking that has not previously received much attention. The emphasis on pellicle transmission has been focused on increasing the average transmission. Much less, attention has been paid to transmission uniformity. This paper explores the total demand on the photospeed latitude budget, the causes of pellicle transmission nonuniformity and examines reasonable expectations for pellicle performance. Modeling is used to examine how the two primary errors in pellicle manufacturing contribute to nonuniformity in transmission. World-class pellicle transmission uniformity standards are discussed and a comparison made between specifications of other components in the photolithographic process. Specifications for other materials or parameters are used as benchmarks to develop a proposed industry standard for pellicle transmission uniformity.

  4. Learned control over spinal nociception: Transfer and stability of training success in a long-term study.

    Science.gov (United States)

    Bäumler, Maximilian; Feller, Moritz; Krafft, Stefanie; Schiffer, Manuela; Sommer, Jens; Straube, Andreas; Weinges, Fabian; Ruscheweyh, Ruth

    2017-12-01

    Healthy subjects can learn to use cognitive-emotional strategies to suppress their spinal nociception, quantified by the nociceptive flexor reflex (RIII reflex), when given visual RIII feedback. This likely reflects learned activation of descending pain inhibition. Here, we investigated if training success persists 4 and 8 months after the end of RIII feedback training, and if transfer (RIII suppression without feedback) is possible. 18 and 8 subjects who had successfully completed feedback training were investigated 4 and 8 months later. At 4 months, RIII suppression during feedback and transfer was similar to that achieved at the final RIII feedback training session (to 50 ± 22%, 53 ± 21% and 52 ± 21% of baseline, all differences n.s.). At 8 months, RIII suppression was somewhat (not significantly) smaller in the feedback run (to 64 ± 17%) compared to the final training session (56 ± 19%). Feedback and transfer runs were similar (to 64 ± 17% vs. 68 ± 24%, n.s.). Concomitant reductions in pain intensity ratings were stable at 4 and 8 months. RIII feedback training success was completely maintained after 4 months, and somewhat attenuated 8 months after training. Transfer was successful. These results are an important pre-requisite for application of RIII feedback training in the context of clinical pain. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  5. Modulation of Cervical Facet Joint Nociception and Pain Attenuates Physical and Psychological Features of Chronic Whiplash: A Prospective Study.

    Science.gov (United States)

    Smith, Ashley Dean; Jull, Gwendolen; Schneider, Geoff M; Frizzell, Bevan; Hooper, Robert A; Sterling, Michele

    2015-09-01

    To investigate changes in clinical (physical and psychological) features of individuals with chronic whiplash-associated disorder who had previously undergone cervical radiofrequency neurotomy at the time point when the effects of radiofrequency neurotomy had dissipated and pain returned. Prospective cohort observational trial of consecutive patients. Tertiary spinal intervention centre in Calgary, Alberta, Canada. A total of 53 consecutive individuals with chronic whiplash-associated disorder. Individuals underwent radiofrequency neurotomy and were assessed before radiofrequency neurotomy, at 1 and 3 months postprocedure, and then after the return of pain (approximately 10 months postprocedure). Quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test), nociceptive flexion reflex, and motor function (cervical range of movement; craniocervical flexion test) were measured. Self-reported disability, psychological distress, pain catastrophization, and posttraumatic stress disorder symptoms also were measured. Upon the return of pain after radiofrequency neurotomy, levels of disability increased (P .22). There were no significant changes in pressure hyperalgesia (P > .054) or craniocervical flexion test performance (P > .07) after the return of pain. Psychological distress and pain catastrophizing increased significantly after the return of pain (P .13). However, there was no difference in number or severity of posttraumatic stress symptoms after the return of pain (P > .30). Physical and psychological features of chronic whiplash-associated disorder are modulated dynamically with cervical radiofrequency neurotomy. These findings indicate that peripheral nociception is involved in the manifestations of chronic whiplash-associated disorder in this cohort of individuals. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  6. Nociceptive thermal threshold testing in horses – effect of neuroleptic sedation and neuroleptanalgesia at different stimulation sites

    Science.gov (United States)

    2013-01-01

    Background Aim of the study was to compare the effect of neuroleptic sedation with acepromazine and neuroleptanalgesia with acepromazine and buprenorphine on thermal thresholds (TT) obtained at the nostrils and at the withers. The study was carried out as a randomized, blinded, controlled trial with cross-over design. Thermal thresholds were determined by incremental contact heat applied to the skin above the nostril (N) or the withers (W). Eleven horses were treated with saline (S), acepromazine (0.05 mg/kg) (ACE) or acepromazine and buprenorphine (0.0075 mg/kg) (AB) intravenously (IV). Single stimulations were performed 15 minutes prior and 15, 45, 75, 105, 165, 225, 285, 405 and 525 minutes after treatment. Sedation score, gastrointestinal auscultation score and occurrence of skin lesions were recorded. Data were analysed with analysis of variance for repeated measurements. Results There were no significant differences in TT between N and W with all treatments. The TT remained constant after S and there was no difference in TT between S and ACE. After AB there was a significant increase above baseline in TT until 405 minutes after treatment. Restlessness occurred 30–90 minutes after AB in 7 horses. All horses had reduced to absent borborygmi after AB administration for 165 to 495 minutes. Conclusion Thermal stimulation at both described body areas gives comparable results in the assessment of cutaneous anti-nociception in horses. There is no differential influence of neuroleptic sedation or neuroleptanalgesia on TTs obtained at N or W. Buprenorphine combined with acepromazine has a long lasting anti-nociceptive effect associated with the typical opioid induced side effects in horses. PMID:23837730

  7. Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

    Science.gov (United States)

    Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

    2012-01-01

    Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a

  8. Specific involvement of atypical PKCζ/PKMζ in spinal persistent nociceptive processing following peripheral inflammation in rat

    Directory of Open Access Journals (Sweden)

    Marchand Fabien

    2011-11-01

    Full Text Available Abstract Background Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of long-term potentiation (LTP, a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCζ/PKMζ in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP. Results Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-ζ pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs following formalin administration. In addition, Complete Freund's Adjuvant (CFA-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCζ/PKMζ activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCζ/PKMζ in dorsal horn neurons, specifically PKMζ phosphorylation in formalin rats. Finally, inhibition of PKCζ/PKMζ activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn. Conclusions These results suggest that PKCζ, especially PKMζ isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation.

  9. Central nociceptive sensitization vs. spinal cord training: Opposing forms of plasticity that dictate function after complete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Adam R Ferguson

    2012-10-01

    Full Text Available The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training. Conversely intradermal formalin impaired future spinal learning (24 h post-injection. Because the NMDA receptor has been implicated in formalin-induced central sensitization, we tested whether pretreatment with NMDA affects spinal learning. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24h. These data provide strong evidence for an

  10. In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

    Directory of Open Access Journals (Sweden)

    D.O. Gonçalves

    2011-02-01

    Full Text Available Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g, which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan, at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively. Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively and second phase (73, 57, and 66% inhibition of licking time, respectively. The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc. Lovastatin (0.01, 0.1, and 1 µg/mL inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α and the inducible form of nitric oxide synthase (iNOS activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

  11. Transmission Integration | Grid Modernization | NREL

    Science.gov (United States)

    Transmission Integration Transmission Integration The goal of NREL's transmission integration integration issues and provide data, analysis, and models to enable the electric power system to more and finding solutions to address them to enable transmission grid integration. Capabilities Power

  12. Series Transmission Line Transformer

    Science.gov (United States)

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  13. Drivers of Tuberculosis Transmission.

    Science.gov (United States)

    Mathema, Barun; Andrews, Jason R; Cohen, Ted; Borgdorff, Martien W; Behr, Marcel; Glynn, Judith R; Rustomjee, Roxana; Silk, Benjamin J; Wood, Robin

    2017-11-03

    Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Jumping in aquatic environment after sciatic nerve compression: nociceptive evaluation and morphological characteristics of the soleus muscle of Wistar rats.

    Science.gov (United States)

    Malanotte, Jéssica Aline; Kakihata, Camila Mayumi Martin; Karvat, Jhenifer; Brancalhão, Rose Meire Costa; Ribeiro, Lucinéia de Fátima Chasko; Bertolini, Gladson Ricardo Flor

    2017-01-01

    To evaluate the effect of jumping in aquatic environment on nociception and in the soleus muscle of trained and not trained Wistar rats, in the treatment of compressive neuropathy of the sciatic nerve. Twenty-five Wistar rats were distributed into five groups: Control, Lesion, Trained + Lesion, Lesion + Exercise, and Trained + Lesion + Exercise. The training was jumping exercise in water environment for 20 days prior to injury, and treatment after the injury. Nociception was evaluated in two occasions, before injury and seven after injury. On the last day of the experiment, the right soleus muscles were collected, processed and analyzed as to morphology and morphometry. In the assessment of nociception in the injury site, the Control Group had higher average than the rest, and the Lesion Group was larger than the Trained + Lesion and Lesion + Exercise Groups. The Control Group showed higher nociceptive threshold in paw, compared to the others. In the morphometric analysis, in relation to Control Group, all the injured groups showed decreased muscle fiber area, and in the Lesion Group was lower than in the Lesion + Exercise Group and Trained + Lesion Group. Considering the diameter of the muscle fiber, the Control Group had a higher average than the Trained + Lesion Group and the Trained + Lesion + Exercise Group; and the Lesion Group showed an average lower than the Trained + Lesion and Lesion + Exercise Groups. Resistance exercise produced increased nociception. When performed prior or after nerve damage, it proved effective in avoiding hypotrophy. The combination of the two protocols led to decrease in diameter and area of the muscle fiber. Avaliar os efeitos do salto em meio aquático, na nocicepção e no músculo sóleo, em ratos Wistar treinados e não treinados, no tratamento de neuropatia compressiva do nervo isquiático. Foram distribuídos em cinco grupos 25 ratos Wistar: Controle, Lesão, Treinado + Lesão, Lesão + Exercício e Treinado + Lesão + Exerc

  15. Cultural Transmission of Civicness

    DEFF Research Database (Denmark)

    Ljunge, Jan Martin

    2012-01-01

    This paper estimates the intergeneration transmission of civicness by studying second generation immigrants in 29 European countries with ancestry in 83 nations. There is significant transmission of civicness both on the mother’s and the father’s side. The estimates are quantitatively significant...

  16. Cultural Transmission of Civicness

    DEFF Research Database (Denmark)

    Ljunge, Jan Martin

    This paper estimates the intergeneration transmission of civicness by studying second generation immigrants in 29 European countries with ancestry in 83 nations. There is significant transmission of civicness both on the mother’s and the father’s side. The estimates are quantitatively significant...

  17. Poverty and price transmission

    DEFF Research Database (Denmark)

    Elleby, Christian

    A key parameter determining the welfare impact from a world market shock is the transmission elasticity which measures the average domestic response to an international price change. Many studies have estimated price transmission elasticities for a large number of countries but the variation in t...

  18. Transmission market support system

    International Nuclear Information System (INIS)

    Reinschmidt, K.F.; Coles, B.C.

    1995-01-01

    An interactive, computer-based market support system has been developed for transmission access that is efficient, equitable, and fair to all parties concerned with electrical transmission: utilities, electric generators, owners of transmission networks, and wholesale purchasers of electrical power. Each participant transmits electronically to the computer system his proposed price schedule for buying, selling, or transmitting power for each future time period. The price for transmission on a single line in one direction can differ from the price in the other direction. The total quantity offered in the transmission bid represents the capacity of the line, and the flow on the line cannot exceed this value. The system automatically computes the prices that clear the market; that is, the price that each generator receives at each bus, the price that each transmission operator receives on each line, and the price that each customer pays at each bus. The computer system maximizes the benefits to all three classes while satisfying the electrical characteristics of the transmission system by means of load flow calculations. Customers never pay more than their bid prices (but may pay less), and generators and transmission operators never receive less than their bid prices (but may receive more). The price at each bus applies to all buyers and sellers at that bus: all buyers at the same bus pay the same price and all generators at a bus receive the same price

  19. Pricing transmission services

    International Nuclear Information System (INIS)

    Haaden, E.

    1995-01-01

    The price structure for transmission of electric power through the main lines in Sweden is analyzed. After deregulation of the electricity market, the main transmission lines are owned by a separate national company, with no interests from the power producers. Comparisons are made to ideal marginal price structures. 6 refs

  20. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.

  1. Electric transmission technology

    International Nuclear Information System (INIS)

    Shah, K.R.

    1990-01-01

    Electric transmission technology has matured and can transmit bulk power more reliably and economically than the technology 10 years ago.In 1882, Marcel Depres transmitted 15 kW electric power at 2 kV, using a constant direct current; present transmission voltages have risen to ± 600 kV direct current (DC) and 765 kV alternating current (AC), and it is now possible to transmit bulk electric power at voltages as high as ± 1000 kV DC and 1500 kV AC. Affordable computer systems are now available to optimize transmission reliably. New materials have reduced the bulk of insulation for lines and equipment. New conducting materials and configurations have reduced losses in transmission. Advances in line structures and conductor motion, understanding of flashover characteristics of insulators and air-gaps and electrical performance of lines have resulted in more compact urban transmission lines. (author). 15 refs., 7 tabs., 11 figs

  2. Microwave energy transmission

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Hiroshi [Kyoto Univ. (Japan)

    1989-03-05

    Laying stress on the technological problems and effect on the environment of microwave energy transmission, recent scientific and engineering problems and related subjects are described. Because no fuel is required for the solar power generation, the power generation system can not be considered as an expensive one when the unit cost of energy is taken into consideration. Some of the important technological problems in the microwave energy transmission are accurate microwave beam control technology to receiving stations and improvement in the efficiency of transmission system. Microwave energy beam has effects on living bodies, communication, and plasma atmosphere of the earth. Microwave energy transmission using a space flyer unit is scheduled. Its objective is the development of microwave wireless transmission technology and the study of the correlation between high power microwave and ionosphere plasma. Experiments on such a small scale application as a microwave driven space ship to bring results seem also important. 12 refs., 13 figs.

  3. Kv4 channels underlie the subthreshold-operating A-type K+-current in nociceptive dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Thanawath R Na Phuket

    2009-07-01

    Full Text Available The dorsal root ganglion (DRG contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling.  Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the molecular correlate of the corresponding A-type K+ current (IA has remained hypothetical.  Kv4 channels may underlie the IA in DRG neurons.  We combined electrophysiology, molecular biology (whole-tissue and single-cell RT-PCR and immunohistochemistry to investigate the molecular basis of the IA in acutely dissociated DRG neurons from 7-8 day-old rats.  Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM and 4-aminopyridine-sensitive (5 mM IA.  Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent.  Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs.  Also, single small-medium diameter DRG neurons (~30 mm exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker.  In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent.  Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2.  Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to IA in DRG neurons.  Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

  4. Handheld mechanical nociceptive threshold testing in dairy cows - intra-individual variation, inter-observer agreement and variation over time.

    Science.gov (United States)

    Raundal, Peter M; Andersen, Pia H; Toft, Nils; Forkman, Björn; Munksgaard, Lene; Herskin, Mette S

    2014-11-01

    To examine the use of handheld methodology to assess mechanical nociceptive threshold (MNT) on cows kept loose-housed. Prospective randomized partial cross-over experimental study. A one-factor (test day) design was used to evaluate MNT over time. One hundred and fifteen healthy, loose-housed Danish Holstein cattle. We evaluated intra-individual variation, inter-observer agreement and variation over time of MNT using two handheld devices and two stimulation sites. Mechanical, ramped stimulations were performed with an algometer (6.5 mm diameter steel probe, 0-10.0 kgf) or an electronic von Frey device (plastic tip with diameter 0.8 mm, 0-1000 gf). Each cow received 5-6 consecutive stimulations within a 2 × 5 cm skin area on the dorsal or lateral aspect of the left third metatarsus until an avoidance reaction occurred. We investigated the difference in precision [expressed as coefficient of variation (CV)] between the combinations of devices and stimulation sites. The inter-observer agreement and the difference in MNT between test day 1, 3, 7, 10 and 24 were investigated for selected combinations. Data were analysed in mixed models and Bland-Altman as relevant. The CVs did not differ [range 0.34-0.52 (p = 0.1)]. Difference between observers (95% limits) was 0.2 kgf (2.8) and 4 gf (369) for the algometer and von Frey device, respectively. Mechanical nociceptive threshold increased from 361 on test day one to 495 gf on test day 24 (p < 0.01). All methods showed a high degree of intra-individual variation, and no combination of device and stimulation site showed superior precision. Mean difference between observers was low, and MNT was not consistent over time. Further development of the methods is required before they can be used in research to investigate possible relations between claw lesions and hyperalgesia. © 2014 The Authors Veterinary Anaesthesia and Analgesia published by John Wiley & Sons Ltd on behalf of Association of Veterinary Anaesthetists and the

  5. Nociceptive afferents to the premotor neurons that send axons simultaneously to the facial and hypoglossal motoneurons by means of axon collaterals.

    Directory of Open Access Journals (Sweden)

    Yulin Dong

    Full Text Available It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG or FG/tetramethylrhodamine-dextran amine (TMR-DA were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA was injected into the caudal spinal trigeminal nucleus (Vc. The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt, dorsal and ventral medullary reticular formation (MdD, MdV, supratrigeminal nucleus (Vsup and parabrachial nucleus (PBN with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals.

  6. Nociception contributes to the formation of myogenic contracture in the early phase of adjuvant-induced arthritis in a rat knee.

    Science.gov (United States)

    Kaneguchi, Akinori; Ozawa, Junya; Moriyama, Hideki; Yamaoka, Kaoru

    2017-07-01

    It is unknown how joint contracture is generated in inflamed joints. This study aimed to clarify the role of nociception on the formation of joint contracture secondary to arthritis. Monoarthritis was induced by intra-articular injections of complete Freund's adjuvant (CFA) into rat knees. On day 5 after CFA injection, the passive extension range of motion (ROM) of knee joints were measured, both before and after myotomy of knee flexors, to evaluate the extent of muscular contribution to CFA-induced joint contracture. The steroidal anti-inflammatory drug dexamethasone could prevent ROM restrictions completely, both before and after myotomy. On the other hand, the opioid analgesic drug morphine did not prevent the development of restricted ROM observed after myotomy, while it did before myotomy. This indicates that nociception contributes to joint contracture through alterations in muscular structure (myogenic factors). Next, we tested the hypothesis that nociception-induced reflexive flexor muscle contractions cause myogenic contracture in arthritic joints. To do this, chemical denervation was performed by Botulinum toxin type A (BTX-A) injections into knee flexor muscles, simultaneously with CFA injections into the knee. As expected, BTX-A could alleviate ROM restrictions observed before myotomy. These findings suggest that nociceptive-related muscle contractions play an essential role in the formation of joint contracture. Thus, our study indicates that analgesic management during an early stage of joint arthritis is an essential mean to prevent the formation of joint contracture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1404-1413, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats.

    Science.gov (United States)

    Mahdi, Harith Jameel; Khan, Nurzalina Abdul Karim; Asmawi, Mohd Zaini Bin; Mahmud, Roziahanim; A/L Murugaiyah, Vikneswaran

    2018-03-01

    The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

  8. Polysaccharide rich fractions from barks of Ximenia americana inhibit peripheral inflammatory nociception in mice Antinociceptive effect of Ximenia americana polysaccharide rich fractions

    Directory of Open Access Journals (Sweden)

    Kaira E.S. da Silva-Leite

    Full Text Available Abstract Ximenia americana L., Olacaceae, barks are utilized in folk medicine as analgesic and anti-inflammatory. The objective was to evaluate the toxicity and antinociceptive effect of polysaccharides rich fractions from X. americana barks. The fractions were obtained by extraction with NaOH, followed by precipitation with ethanol and fractionation by ion exchange chromatography. They were administered i.v. or p.o. before nociception tests (writhing, formalin, carragenan-induced hypernociception, hot plate, or during 14 days for toxicity assay. The total polysaccharides fraction (TPL-Xa: 8.1% yield presented 43% carbohydrate (21% uronic acid and resulted in two main fractions after chromatography (FI: 12%, FII: 22% yield. FII showed better homogeneity/purity, content of 44% carbohydrate, including 39% uronic acid, arabinose and galactose as major monosaccharides, and infrared spectra with peaks in carbohydrate range for COO- groups of uronic acid. TPL-Xa (10 mg/kg and FII (0.1 and 1 mg/kg presented inhibitory effect in behavior tests that evaluate nociception induced by chemical and mechanical, but not thermal stimuli. TPL-Xa did not alter parameters of systemic toxicity. In conclusion, polysaccharides rich fractions of X. americana barks inhibit peripheral inflammatory nociception, being well tolerated by animals.

  9. Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.

    Science.gov (United States)

    Morado-Urbina, Carlos Eduardo; Alvarado-Vázquez, Perla Abigail; Montiel-Ruiz, Rosa Mariana; Acosta-González, Rosa Issel; Castañeda-Corral, Gabriela; Jiménez-Andrade, Juan Miguel

    2014-11-01

    This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities. © 2014 Wiley Periodicals, Inc.

  10. Evidence of altered pressure pain thresholds in persons with disorders of consciousness as measured by the Nociception Coma Scale-Italian version.

    Science.gov (United States)

    Sattin, Davide; Schnakers, Caroline; Pagani, Marco; Arenare, Francesca; Devalle, Guya; Giunco, Fabrizio; Guizzetti, GianBattista; Lanfranchi, Maurizio; Giovannetti, Ambra M; Covelli, Venusia; Bersano, Anna; Nigri, Anna; Minati, Ludovico; Rossi Sebastiano, Davide; Parati, Eugenio; Bruzzone, MariaGrazia; Franceschetti, Silvana; Leonardi, Matilde

    2017-02-28

    Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.

  11. Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.

    Directory of Open Access Journals (Sweden)

    Stéphanie Ventéo

    Full Text Available Dorsal root ganglia (DRGs contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury.

  12. Cost characteristics of transmission

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    FERC regulation of transmission is predicated, at least in part, on a belief that, in the absence of regulation, some utilities would be able to exercise monopoly power and the ability to extract monopoly profits. This monopoly power follows from the view that transmission facilities inevitably are a natural monopoly for both economic and social/regulatory reasons. In the first part of this section the authors present the argument that transmission is a natural monopoly. They then consider the impact of this on regulation and the problems that that view creates

  13. Understanding Ebola Virus Transmission

    Directory of Open Access Journals (Sweden)

    Seth Judson

    2015-02-01

    Full Text Available An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus.

  14. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

    Directory of Open Access Journals (Sweden)

    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  15. [Assessment of nociceptive suppression in laparoscopic postoperative status: prospective, randomized and comparative study with a control group].

    Science.gov (United States)

    Jaime, A; Hernández-Favela, P; Zamora, R; Nava, E; Barroso, G; Kably, A

    2001-08-01

    In recent years endoscopic surgery has became a highly demanded procedure because it is an easy method for diagnosis and treatment in gynecological field. Post-operative pain is considered as a condition in the morbidity status. The objective of this study was to evaluate the nociceptive suppression in laparoscopic surgery. A prospective randomized trial was performed in order to evaluate this condition. A total of 45 patients were included. Three groups were randomized using two different anesthetics applied in the cult-de-sac and uterine-bladder union. Group A (n-15) received bupivacaine, group B (n = 15) ropivacaine and group C (control) saline solution was instilled. The pain was scored using the visual analog scale as same as blood pressure and heart rate in a 15 minute intervals in the recovery room. For study design there were no differences in age, weight, height and body mass index (EMI). The surgical and anesthetic times were similar among groups. However there were significant differences when pain was evaluated. For a less toxic effects and good preventive analgesia we recommend to use ropivacaine in the postoperative status.

  16. Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex.

    Directory of Open Access Journals (Sweden)

    José A Biurrun Manresa

    Full Text Available The aim of this study was to determine the reliability of the conditioned pain modulation (CPM paradigm assessed by an objective electrophysiological method, the nociceptive withdrawal reflex (NWR, and psychophysical measures, using hypothetical sample sizes for future studies as analytical goals. Thirty-four healthy volunteers participated in two identical experimental sessions, separated by 1 to 3 weeks. In each session, the cold pressor test (CPT was used to induce CPM, and the NWR thresholds, electrical pain detection thresholds and pain intensity ratings after suprathreshold electrical stimulation were assessed before and during CPT. CPM was consistently detected by all methods, and the electrophysiological measures did not introduce additional variation to the assessment. In particular, 99% of the trials resulted in higher NWR thresholds during CPT, with an average increase of 3.4 mA (p<0.001. Similarly, 96% of the trials resulted in higher electrical pain detection thresholds during CPT, with an average increase of 2.2 mA (p<0.001. Pain intensity ratings after suprathreshold electrical stimulation were reduced during CPT in 84% of the trials, displaying an average decrease of 1.5 points in a numeric rating scale (p<0.001. Under these experimental conditions, CPM reliability was acceptable for all assessment methods in terms of sample sizes for potential experiments. The presented results are encouraging with regards to the use of the CPM as an assessment tool in experimental and clinical pain. Trial registration: Clinical Trials.gov NCT01636440.

  17. Heart rate variability analysis as an index of emotion regulation processes: interest of the Analgesia Nociception Index (ANI).

    Science.gov (United States)

    De Jonckheere, J; Rommel, D; Nandrino, J L; Jeanne, M; Logier, R

    2012-01-01

    Autonomic Nervous System (ANS) variations are strongly influence by emotion regulation processes. Indeed, emotional stimuli are at the origin of an activation of the ANS and the way an individual pass from a state of alert in the case of emotional situation to a state of calm is closely coupled with the ANS flexibility. We have previously described and developed an Analgesia Nociception Index (ANI) for real time pain measurement during surgical procedure under general anesthesia. This index, based on heart rate variability analysis, constitutes a measure of parasympathetic tone and can be used in several other environments. In this paper, we hypothesized that such an index could be used as a tool to investigate the processes of emotional regulation of a human subject. To test this hypothesis, we analyzed ANI's response to a negative emotional stimulus. This analysis showed that the index decreases during the emotion induction phase and returns to its baseline after 2 minutes. This result confirms that ANI could be a good indicator of parasympathetic changes in emotional situation.

  18. Transmissions in vehicles 2010

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    Within the international VDI congress 'Gears in vehicles 2010' of the VDI Wissensforum GmbH (Duesseldorf, Federal Republic of Germany) between 22nd and 23rd June, 2010, in Friedrichshafen (Federal Republic of Germany), the following lectures were held: (1) 8HP70H - The moldhybrid transmission from ZF - Cjallenges and achievements (P. Gutmann); (2) GETRAG boosted range extender - A highly flexible electric powertrain for maximum CO{sub 2} reduction (S. Huepkes); (3) E-Transmission between full-hybrid and E-drive (P. Tenberge); (4) Reducing NO{sub x} and particulate emissions in electrified drivelines (R. Kuberczyk); (5) Simulation aided HEV and EV development: from the component to the whole powertrain (A. Gacometti); (6) Investigations on operating behaviour of the optimized CVT hybrid driveline (B.-R. Hoehn); (7) Customer-oriented dimensioning of electrified drivetrains (M. Eghtessad); (8) Decentralized optimal control strategy for parallel hybrid electric vehicles (A. Frenkel); (9) The new generation 6-speed automatic transmission AF40 (G. Bednarek); (10) Customized mechatronic solutions for integrated transmission control units (M. Wieczorek); (11) The optimal automatic transmission for front-transverse applications - Planetary transmissions or dual clutch transmissions? (G. Gumpoltsberger); (12) The new shift-by-wire gearshift lever for the Audi A8 - Requirements and concept (T. Guttenbergere); (13) The new shift-by-wire gearshift lever for the Audi A8 - Realization (A. Giefer); (14) Fuel-efficient transmissions of the future: Calculation of the efficiency factor for vehicle transmissions (B. Volpert); (15) HT-ACM: A new polymer generation for static and dynamic gearbox sealing solutions (E. Osen); (16) 'Energy efficiency equipped solutions by SKF' for power train applications - A contribution to CO{sub 2} - emission reduction and sustainability (T. Bobke); (17) 6-Ratio planetary shift transmission controlled by 4 external brakes, and design

  19. Transmission issues in Alberta

    International Nuclear Information System (INIS)

    Levson, D.

    2002-01-01

    This paper outlined the major issues and concerns facing users of the transmission system in Alberta. They include congestion management issues that make investors uncertain about power generation. It is necessary to know the difference between which transmission price signals will be faced by low cost cogeneration at Fort McMurray and Cold Lake coal-fired generation near Edmonton compared to combined cycle gas generation near Calgary. Import and export policy tariffs are another concern. Most new generation opportunities in Alberta require access to export markets, but transmission facilities for export need policy support and appropriate tariffs. It was noted that the past actions of Alberta's Transmission Administrator and balancing pool may be distorting market signals for ancillary service markets, and that loss studies and calculations need upgrading

  20. Kansas Electric Transmission Lines

    Data.gov (United States)

    Kansas Data Access and Support Center — This data set is a digital representation of the EletcircTransmission lines for the State of Kansas as maintained by the Kansas Corporation Commission. Data is...

  1. ECRH transmission system

    International Nuclear Information System (INIS)

    Tancredi, J.

    1983-01-01

    Hughes, Electron Dynamics Division is developing gyrotrons for ECRH requirements. In the development program, techniques have been evolved for transmission system components. These techniques include over-moded waveguide tapers, high average power windows, and rf water loads for testing

  2. Electric Power Transmission Lines

    Data.gov (United States)

    Department of Homeland Security — Transmission Lines are the system of structures, wires, insulators and associated hardware that carry electric energy from one point to another in an electric power...

  3. Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

    Science.gov (United States)

    da Silva Arrigo, Jucicléia; Balen, Eloise; Júnior, Ubirajara Lanza; da Silva Mota, Jonas; Iwamoto, Renan Donomae; Barison, Andersson; Sugizaki, Mario Mateus; Leite Kassuya, Cândida Aparecida

    2016-02-17

    Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The

  4. Airspace: Antarctic Sound Transmission

    OpenAIRE

    Polli, Andrea

    2009-01-01

    This paper investigates how sound transmission can contribute to the public understanding of climate change within the context of the Poles. How have such transmission-based projects developed specifically in the Arctic and Antarctic, and how do these works create alternative pathways in order to help audiences better understand climate change? The author has created the media project Sonic Antarctica from a personal experience of the Antarctic. The work combines soundscape recordings and son...

  5. Offshore Transmission Technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-10-15

    The purpose of this document is to give an overview of offshore electricity transmission technologies. In particular this document is concerned with the use of High Voltage Direct Current (HVDC) systems and more specifically with the development of Voltage Source Converter (VSC) technology. This report outlines the current state of the main technology groups required for offshore HVDC transmission as well as giving examples of offshore projects (both current and future). Finally some indications of likely unit costs for HV assets are given.

  6. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.  Created: 11/26/2012 by Division of HIV/AIDS Prevention.   Date Released: 11/26/2012.

  7. Optical analog transmission device

    International Nuclear Information System (INIS)

    Ikawa, Shinji.

    1994-01-01

    The present invention concerns a device such as electro-optical conversion elements, optoelectric-electric elements and optical transmission channel, not undergoing deleterious effects on the efficiency of conversion and transmission due to temperature, and aging change. That is, a sine wave superposing means superposes, on a detector signal to be transmitted, a sine-wave signal having a predetermined amplitude and at a frequency lower than that of the detector signal. An optoelectric conversion means converts the electric signal as the signal of the sine-wave signal superposing means into an optical signal and outputs the same to an optical transmitting channel. The optoelectric conversion means converts the transmitted signal to an electric signal. A discriminating means discriminates the electric signal into a detector signal and a sine-wave signal. A calculating means calculates an optical transmitting efficiency of the transmitting channel based on the amplitude of the discriminated sine-wave signal. A processing means compensates an amplitude value of the detector signals discriminated by the discriminating means based on the optical transmission efficiency. As a result, an optical analog transmission device can be attained, which conducts optical transmission at a high accuracy without undergoing the defective effects of the optical transmission efficiency. (I.S.)

  8. National transmission grid study

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, Spencer [USDOE Office of the Secretary of Energy, Washington, DC (United States)

    2003-05-31

    The National Energy Policy Plan directed the U.S. Department of Energy (DOE) to conduct a study to examine the benefits of establishing a national electricity transmission grid and to identify transmission bottlenecks and measures to address them. DOE began by conducting an independent analysis of U.S. electricity markets and identifying transmission system bottlenecks using DOE’s Policy Office Electricity Modeling System (POEMS). DOE’s analysis, presented in Section 2, confirms the central role of the nation’s transmission system in lowering costs to consumers through increased trade. More importantly, DOE’s analysis also confirms the results of previous studies, which show that transmission bottlenecks and related transmission system market practices are adding hundreds of millions of dollars to consumers’ electricity bills each year. A more detailed technical overview of the use of POEMS is provided in Appendix A. DOE led an extensive, open, public input process and heard a wide range of comments and recommendations that have all been considered.1 More than 150 participants registered for three public workshops held in Detroit, MI (September 24, 2001); Atlanta, GA (September 26, 2001); and Phoenix, AZ (September 28, 2001).

  9. Wireless data signal transmission system

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to a method for providing a radio frequency signal for transmission, a system for providing a radio frequency signal for transmission and a method for wireless data transmission between a transmitter and a receiver.......The present invention relates to a method for providing a radio frequency signal for transmission, a system for providing a radio frequency signal for transmission and a method for wireless data transmission between a transmitter and a receiver....

  10. Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.

    Science.gov (United States)

    Peng, H-Z; Ma, L-X; Lv, M-H; Hu, T; Liu, T

    2016-04-05

    Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial.

    Science.gov (United States)

    Upton, Henry D; Ludbrook, Guy L; Wing, Andrew; Sleigh, Jamie W

    2017-07-01

    The "Analgesia Nociception Index" (ANI; MetroDoloris Medical Systems, Lille, France) is a proposed noninvasive guide to analgesia derived from an electrocardiogram trace. ANI is scaled from 0 to 100; with previous studies suggesting that values ≥50 can indicate adequate analgesia. This clinical trial was designed to investigate the effect of intraoperative ANI-guided fentanyl administration on postoperative pain, under anesthetic conditions optimized for ANI functioning. Fifty patients aged 18 to 75 years undergoing lumbar discectomy or laminectomy were studied. Participants were randomly allocated to receive intraoperative fentanyl guided either by the anesthesiologist's standard clinical practice (control group) or by maintaining ANI ≥50 with boluses of fentanyl at 5-minute intervals (ANI group). A standardized anesthetic regimen (sevoflurane, rocuronium, and nonopioid analgesia) was utilized for both groups. The primary outcome was Numerical Rating Scale pain scores recorded from 0 to 90 minutes of recovery room stay. Secondary outcomes included those in the recovery room period (total fentanyl administration, nausea, vomiting, shivering, airway obstruction, respiratory depression, sedation, emergence time, and time spent in the recovery room) and in the intraoperative period (total fentanyl administration, intraoperative-predicted fentanyl effect-site concentrations over time [CeFent], the correlation between ANI and predicted CeFent and the incidence of movement). Statistical analysis was performed with 2-tailed Student t tests, χ tests, ordinal logistic generalized estimating equation models, and linear mixed-effects models. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes. Over the recovery room period (0-90 minutes) Numerical Rating Scale pain scores were on average 1.3 units lower in ANI group compared to the control group (95% confidence interval [CI], -0.4 to 2.4; P= .01). Patients in the ANI group

  12. Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model

    Directory of Open Access Journals (Sweden)

    Zhi-Hong Wen

    2012-08-01

    Full Text Available Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the analgesic properties of sinularin based on in vivo experiments. In the present study, we found that sinularin significantly inhibits the upregulation of proinflammatory proteins, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2 and upregulates the production of transforming growth factor-β (TGF-β in lipopolysaccharide (LPS-stimulated murine macrophage RAW 264.7 cells according to western blot analysis. We found that subcutaneous (s.c. administration of sinularin (80 mg/kg 1 h before carrageenan injection significantly inhibited carrageenan-induced nociceptive behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia, and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg significantly inhibited carrageenan-induced microglial and astrocyte activation as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord. Moreover, s.c. sinularin (80 mg/kg inhibited carrageenan-induced tissue inflammatory responses, redness and edema of the paw, and leukocyte infiltration. The results of immunohistochemical studies indicate that s.c. sinularin (80 mg/kg could upregulate production of TGF-β1 in carrageenan-induced inflamed paw tissue. The present results demonstrate that systemic sinularin exerts analgesic effects at the behavioral and spinal levels, which are associated with both inhibition of leukocyte infiltration and upregulation of TGF-β1.Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the

  13. The Nociceptive and Anti-Inflammatory Effects of Artemisia dracunculus L. Aqueous Extract on Fructose Fed Male Rats

    Directory of Open Access Journals (Sweden)

    Shahraki Mohammad Reza

    2015-01-01

    Full Text Available Aim & Objective. Artemisia dracunculus L. (Tarragon species have been used as a traditional medicine. The present study was designed to evaluate the nociceptive and anti-inflammatory effects of A. dracunculus L. leaf aqueous extract on fructose drinking water (FDW in male rats. Materials & Methods. Forty-eight Wistar-albino male rats weighing 200–250 g were divided into control (C, control extract (CE, FDW, and FDWE groups (n=12. Group C did not receive any agents; Group CE did 100 mg/kg A. dracunculus L. aqueous extract on a daily basis for duration of four weeks. FDW Group received fructose drinking water (10%, weight/volume but did not receive any agents during trial period. FDWE group received 100 mg/kg A. dracunculus L. aqueous extract during trial period. At the end of experiment, a biphasic pain response was induced following interplanetary injection of formalin (50 µL, 1%. Obtained data were analyzed using SPSS software version 17 and using ANOVA and Tukey post hoc tests. Results were expressed as mean ± SE. Statistical differences were considered significant at P<0.05. Results. Our findings revealed that acute and chronic pain scores in FDW group are significantly higher than other ones and A. dracunculus L. aqueous extract causes significant decreasing of this parameter in FDWE group (P<0.001. Moreover, IL6 and TNF values in this group were significantly decreased compared to FDW group (P<0.05. Conclusion. Results in the present study show that FDW causes the pain response score to increase and cause proinflammatory cytokines in rat model but A. dracunculus L. leaf aqueous extract improves values of these parameters.

  14. Antidepressant, anxiolytic and anti-nociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch leaves in mice model

    Directory of Open Access Journals (Sweden)

    Mohammad Shah Hafez Kabir

    2015-11-01

    Full Text Available Objective: To estimate the antidepressant, anxiolytic and antinociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch (S. colocasiifolia leaves. Methods: Swiss albino mice treated with 1% Tween solution, standard drugs and ethanol extract of S. colocasiifolia, respectively, were subjected to the neurological and antinociceptive investigations. The tail suspension test and forced swimming test were used for testing antidepressant activity, where the parameter is the measurement of immobility time. Anxiolytic activity was evaluated by hole board model. Anti-nociceptive potential of the extract was also screened for centrally acting analgesic activity by using formalin induced licking response model and acetic acid induced writhing test was used for testing peripheral analgesic action. Results: Ethanol extract of S. colocasiifolia significantly decreased the period of immobility in both tested models (tail suspension and forced swimming models of antidepressant activity. In the hole board model, there was a dose dependant (at 100 and 200 mg/kg and a significant increase in the number of head dipping by comparing with control (1% Tween solution (P < 0.05 and P < 0.001. In formalin induced licking model, a significant inhibition of pain compared to standard diclofenac sodium was observed (P < 0.05 and P < 0.001. In acetic acid induced test, there was a significant reduction of writhing response and pain in mice treated with leaves extract of S. colocasiifolia at 200 mg/kg body weight (P < 0.05 and P < 0.001. Conclusions: The results proofed the prospective antidepressant, anxiolytic and antinociceptive activities of ethanol extract of S. colocasiifolia leaves.

  15. Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat.

    Science.gov (United States)

    Zhang, X-L; Albers, K M; Gold, M S

    2015-01-22

    The goals of the present study were to determine (1) the properties of the nicotinic acetylcholine receptor (nAChR) currents in rat cutaneous dorsal root ganglion (DRG) neurons; (2) the impact of nAChR activation on the excitability of cutaneous DRG neurons; and (3) the impact of inflammation on the density and distribution of nAChR currents among cutaneous DRG neurons. Whole-cell patch-clamp techniques were used to study retrogradely labeled DRG neurons from naïve and complete Freund's adjuvant inflamed rats. Nicotine-evoked currents were detectable in ∼70% of the cutaneous DRG neurons, where only one of two current types, fast or slow currents based on rates of activation and inactivation, was present in each neuron. The biophysical and pharmacological properties of the fast current were consistent with nAChRs containing an α7 subunit while those of the slow current were consistent with nAChRs containing α3/β4 subunits. The majority of small diameter neurons with fast current were IB4- while the majority of small diameter neurons with slow current were IB4+. Preincubation with nicotine (1 μM) produced a transient (1 min) depolarization and increase in the excitability of neurons with fast current and a decrease in the amplitude of capsaicin-evoked current in neurons with slow current. Inflammation increased the current density of both slow and fast currents in small diameter neurons and increased the percentage of neurons with the fast current. With the relatively selective distribution of nAChR currents in putative nociceptive cutaneous DRG neurons, our results suggest that the role of these receptors in inflammatory hyperalgesia is likely to be complex and dependent on the concentration and timing of acetylcholine release in the periphery. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Modulates Purinoceptor-Coupled Calcium Signaling and Murine Nociceptive Behavior.

    Science.gov (United States)

    Liu, Pei-Shan; Chueh, Sheau-Huei; Chen, Chin-Chu; Lee, Li-Ya; Shiu, Li-Yen

    2017-01-01

    Hericium erinaceus is well known for the neurotrophic effect it confers by promoting nerve growth factor biosynthesis. We discovered a novel bioactivity of H. erinaceus in its ability to suppress adenosine triphosphate (ATP)-induced calcium signaling in neuronal PC12 cells. ATP, known primarily as a neurotransmitter, also acts on purinoceptors (P2 purinergic receptor [P2R]) to generate the cellular calcium signaling and secretion that mediate P2R physiological manifestations, including pain. Chronic pain reduces quality of life. However, constant analgesic administration can cause liver and kidney injury, as well as loss of the analgesic effect because of desensitization. In this study we investigated the analgesic potential of H. erinaceus through measurements of ATP-induced Ca2+ signaling in cell lines and observation of pain behaviors in mice. In P2R-coupled Ca2+ signaling measurements, extracts of H. erinaceus mycelia (HEEs) blocked ATP-induced Ca2+ signaling in both rat PC12 cells and human HOS cells. HEEs completely blocked ATP-induced Ca2+ signaling in human HOS cells, suggesting that this effect of HEEs is exerted through the P2R subtypes present in HOS cells, which include the P2X4, P2X7, P2Y2, and P2Y4 subtypes. In observations of animal behavior during pain, HEEs significantly reduced heat-induced pain, including postponing both the tail-flick response to heat stimulation and the paw-lifting response to a hot plate. This study demonstrates novel characteristics of H. erinaceus in reducing nociceptive behavior and blocking the functional activity of P2R. Further studies are required to verify this linkage and its molecular mechanisms.

  17. The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord

    Directory of Open Access Journals (Sweden)

    Philip Tröster

    2018-02-01

    Full Text Available A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli.

  18. Transmission line capital costs

    International Nuclear Information System (INIS)

    Hughes, K.R.; Brown, D.R.

    1995-05-01

    The displacement or deferral of conventional AC transmission line installation is a key benefit associated with several technologies being developed with the support of the U.S. Department of Energy's Office of Energy Management (OEM). Previous benefits assessments conducted within OEM have been based on significantly different assumptions for the average cost per mile of AC transmission line. In response to this uncertainty, an investigation of transmission line capital cost data was initiated. The objective of this study was to develop a database for preparing preliminary estimates of transmission line costs. An extensive search of potential data sources identified databases maintained by the Bonneville Power Administration (BPA) and the Western Area Power Administration (WAPA) as superior sources of transmission line cost data. The BPA and WAPA data were adjusted to a common basis and combined together. The composite database covers voltage levels from 13.8 to 765 W, with cost estimates for a given voltage level varying depending on conductor size, tower material type, tower frame type, and number of circuits. Reported transmission line costs vary significantly, even for a given voltage level. This can usually be explained by variation in the design factors noted above and variation in environmental and land (right-of-way) costs, which are extremely site-specific. Cost estimates prepared from the composite database were compared to cost data collected by the Federal Energy Regulatory Commission (FERC) for investor-owned utilities from across the United States. The comparison was hampered because the only design specifications included with the FERC data were voltage level and line length. Working within this limitation, the FERC data were not found to differ significantly from the composite database. Therefore, the composite database was judged to be a reasonable proxy for estimating national average costs

  19. Transmission positron microscopes

    International Nuclear Information System (INIS)

    Doyama, Masao; Kogure, Yoshiaki; Inoue, Miyoshi; Kurihara, Toshikazu; Yoshiie, Toshimasa; Oshima, Ryuichiro; Matsuya, Miyuki

    2006-01-01

    Immediate and near-future plans for transmission positron microscopes being built at KEK, Tsukuba, Japan, are described. The characteristic feature of this project is remolding a commercial electron microscope to a positron microscope. A point source of electrons kept at a negative high voltage is changed to a point source of positrons kept at a high positive voltage. Positional resolution of transmission microscopes should be theoretically the same as electron microscopes. Positron microscopes utilizing trapping of positrons have always positional ambiguity due to the diffusion of positrons

  20. ETR transmission systems

    International Nuclear Information System (INIS)

    Metzler, D.

    1983-01-01

    The presentation concentrates on factors associated with transmission systems for reactors and/or reactor relevant devices. For present day mirrors and their upgrades where power levels are in the few hundred kW range, waveguide systems with mode control are preferred. Beyond the early 1990's time frame are the ETR DEMO and reactor devices. These require injected power levels of about 75 MW. If only power oscillators are available at that time, then a MARS like transmission system may be appropriate or possibly a guided wave waveguide

  1. Transmission grid security

    CERN Document Server

    Haarla, Liisa; Hirvonen, Ritva; Labeau, Pierre-Etienne

    2011-01-01

    In response to the growing importance of power system security and reliability, ""Transmission Grid Security"" proposes a systematic and probabilistic approach for transmission grid security analysis. The analysis presented uses probabilistic safety assessment (PSA) and takes into account the power system dynamics after severe faults. In the method shown in this book the power system states (stable, not stable, system breakdown, etc.) are connected with the substation reliability model. In this way it is possible to: estimate the system-wide consequences of grid faults; identify a chain of eve

  2. Towards an optimal transmission system

    International Nuclear Information System (INIS)

    Calviou, M.

    2005-01-01

    This presentation provided background on National Grid USA and discussed transmission investment in the United States (US) and United Kingdom. It also discussed barriers to transmission investments and improvements, thoughts on solutions and a long-term vision. The presentation identified that transmission investment should follow from clear reliability rules designed to promote better operation and management; investment does not necessarily mean new rights-of-way; and transmission investment should target benefits to customers. It was stated that US transmission investment levels have decreased. A comparison between US and UK transmission investment was presented along with a chart of increasing US congestion costs. Barriers to investment in US transmission include vertical integration; misperception of transmission as a market product; federal and state jurisdiction issues; fragmentation in transmission ownership and operation; rate cap based plans that impact transmission; lack of clarity in cost allocation; and the site selection process. Possible solutions include policy and incentives, promoting independence and resolving structural issues. tabs., figs

  3. 3,6-Dimethoxy-6″,6″-Dimethyl-(7,8,2″,3″)-Chromeneflavone, a Flavonoid Isolated from Lonchocarpus Araripensis Benth. (Fabaceae), Reduces Nociceptive Behaviour in Mice.

    Science.gov (United States)

    Almeida, Jackson R G S; Silva, Juliane C; Guimarães, Amanda L; Oliveira, Ana P; Souza, Grasielly R; Oliveira-Júnior, Raimundo G; Lima-Saraiva, Sarah R G; Barbosa-Filho, José M; Braz-Filho, Raimundo; Queiroz, Dinalva Brito; Botelho, Marco Antônio

    2015-10-01

    Lonchocarpus araripensis Benth. is largely distributed in the northeast region of Brazil. It is popularly known as 'sucupira'. Recent studies have shown that some species of Lonchocarpus have interesting pharmacological activities. In this study, we evaluated the antinociceptive effect of a flavone isolated from L. araripensis. The chemical examination resulted in the isolation of 3,6-dimethoxy-6″,6″-dimethyl-(7,8,2″,3″)-chromeneflavone (DDF). The structure of the compound was established by spectral analysis. Antinociceptive activity of DDF was evaluated by measuring nociception by acetic acid, formalin and hot plate tests. The rota rod test was used to evaluate motor coordination. The results demonstrated that DDF was able to prevent acetic-acid-writhing-induced nociception (p < 0.001) in mice. Furthermore, DDF produced a significant reduction of the nociceptive behaviour at the early and late phases of paw licking in the formalin test. Also, DDF produced an inhibition of the nociceptive behaviour during a hot-plate test. No alteration in motor coordination was observed. These results confirm the hypothesis that DDF reduces the nociceptive behaviour in mice, probably through central mechanisms, but without compromising the motor coordination of animals. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Watching Handball Transmissions

    DEFF Research Database (Denmark)

    Frandsen, Kirsten

    2010-01-01

    and competent when mastering the game and in relation to others. The study shows that entertainment concerns both affective involvement and identity formation, as social and cultural meaning seem to be at the root of involvement. Even though both men and women find great joy in the transmissions, their viewing...

  5. Intergenerational Transmission of Volunteering

    NARCIS (Netherlands)

    Bekkers, René

    2007-01-01

    In this article, I investigate the strength of intergenerational transmission of volunteering for non-profit associations in The Netherlands. Data from the Family Survey of the Dutch Population 2000 reveal that there are significant relations between current volunteering and parental volunteering in

  6. Open access to transmission

    International Nuclear Information System (INIS)

    Keith, D.M.

    1996-01-01

    For the past 12 to 15 years, the US electric power and energy industry and its federal regulators have been going through a prolonged exercise leading to opening up the national interconnected transmission grid for all qualified wholesale users to have open and equal access. The debates have been painful in a sense that not all parties - especially some of the transmission system owning utilities - believe that the concept of Open Access is achievable, due to technical constraints on the systems. The present Open Access activity is limited to wholesales transaction under the federal jurisdiction, but several states are either experimenting with or considering retail wheeling. In fact, the FERC - Federal Energy Regulatory Commission - has already expanded its view to embrace retail transmission, if the retail transaction involves the use of the interstate transmission systems which are under FERC's jurisdiction. This paper delves into some of the results of the technical cost and pricing analysis for open access. The statutes and resulting regulations are not addressed herein. (author). 1 fig

  7. Intergenerational transmission of volunteerism

    NARCIS (Netherlands)

    Bekkers, R.H.F.P.

    2007-01-01

    In this article, I investigate the strength of intergenerational transmission of volunteering for non-profit associations in The Netherlands. Data from the Family Survey of the Dutch Population 2000 reveal that there are significant relations between current volunteering and parental volunteering in

  8. Ventrolateral periaqueductal gray lesion attenuates nociception but does not change anxiety-like indices or fear-induced antinociception in mice.

    Science.gov (United States)

    Mendes-Gomes, Joyce; Amaral, Vanessa Cristiane Santana; Nunes-de-Souza, Ricardo Luiz

    2011-06-01

    The exposure of rodents to an open elevated plus-maze (oEPM: four open arms raised from the floor) elicits naloxone-insensitive antinociception. Midazolam infusion into the dorsal portion of the periaqueductal gray (dPAG), a structure of the descending inhibitory system of pain, failed to alter oEPM-induced antinociception. Chemical lesion of dorsomedial and dorsolateral PAG attenuated defensive behavior in the standard EPM (sEPM), an animal model of anxiety, but failed to change oEPM-induced antinociception. The present study investigated the effects of bilateral lesion, with the injection of NMDA (N-methyl-D-aspartic acid), of the ventrolateral column of PAG (vlPAG) (i) on nociceptive response induced by 2.5% formalin injected into the right hind paw (nociception test) in mice exposed to the enclosed EPM (eEPM: four enclosed arms - a non-aversive situation) or to the oEPM and (ii) on anxiety indices in mice exposed to the sEPM without prior formalin injection. Results showed that oEPM-induced antinociception was not altered by lesion of vlPAG. Nevertheless, the lesion reduced the nociceptive response in mice exposed to the eEPM and increased general locomotor activity during the eEPM and oEPM exposure. Furthermore, vlPAG lesion did not alter anxiety-like indices in mice exposed to the sEPM. The results suggest that vlPAG does not play a role in oEPM-induced antinociception or in defensive reactions assessed in the sEPM. Moreover, vlPAG inactivation induces pain inhibition in mice not exposed to an aversive situation and seems to increase general activity. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

    Science.gov (United States)

    Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

    2012-09-01

    Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Chemical composition and anti-inflamatory, anti-nociceptive and antipyretic activity of rhizome essential oil of Globba sessiliflora Sims. collected from Garhwal region of Uttarakhand

    Directory of Open Access Journals (Sweden)

    Ravendra Kumar

    2017-07-01

    Full Text Available Background & Aim: Family Zingiberaceae is worldwide in distribution. Plants of the zingiberaceae family are used in traditional herbal folk medicine besides their uses in spices, cosmetic, ornamental, food preservatives etc. In Uttarakhand the herbs grow from sub-tropical to temperate region. Globba sessiliflora Simsrhizomes were collected at maturity stage in November from Garhwal region of Uttarakhand, India. In present communication the medicinal use of various zingiberaceous herb provoked us to study the chemical diversity and pharmacological activity determination of this important traditional herb. Experimental: The essential oil was extracted using hydrodistillation method and analyzed by GC-MS. Anti-inflamatory, anti-nociceptive and antipyretic activities of essential oil were experimently determined using mice model. Results: The major compounds identified were β-eudesmol (27.6%, (E-β-caryophyllene (24.3%, α-humulene (3.0%, (6E-nerolidol (4.1%, caryophyllene oxide (9.7%, γ-eudesmol (6.4% and τ-muurolol (8.3% besides other minor constituents. Essential oil of G. sessiliflora rhizome showed good anti-inflamatory, anti-nociceptive and antipyretic activities at the dose level of 100 mg/kg body weight. The oral administration of the essential oil exhibited no toxicity at 400, 600 and 800 mg/kg b.wt. concentration. Ibuprofen, indomthacin and paracetamol were used as standard drugs for comparison. Recommended applications/industries: G. sessiliflora essential oil can be used as herbal remedy for its nontoxicityanti-inflamatory, anti-nociceptive and antipyretic activities.

  11. Mechanisms, Transmissions and Applications

    CERN Document Server

    Corves, Burkhard

    2012-01-01

    The first Workshop on Mechanisms, Transmissions and Applications -- MeTrApp-2011 was organized by the Mechatronics Department at the Mechanical Engineering Faculty, “Politehnica” University of Timisoara, Romania, under the patronage of the IFToMM Technical Committees Linkages and Mechanical Controls and Micromachines. The workshop brought together researchers and students who work in disciplines associated with mechanisms science and offered a great opportunity for scientists from all over the world to present their achievements, exchange innovative ideas and create solid international links, setting the trend for future developments in this important and creative field. The topics treated in this volume are mechanisms and machine design, mechanical transmissions, mechatronic and biomechanic applications, computational and experimental methods, history of mechanism and machine science and teaching methods.

  12. Wireless transmission of power

    International Nuclear Information System (INIS)

    Grotz, T.

    1991-01-01

    This paper reports that it has been proven by researchers that electrical energy can be propagated around the world between the surface of the Earth and the ionosphere at extremely low frequencies in what is known as the Schumann Cavity. Experiments to data have shown that electromagnetic waves with frequencies in the range of 8 Hz, the fundamental Schumann Resonance frequency, propagate with litter attenuation around the planet within the Schumann Cavity. It is the intent of this research to determine if the Schumann Cavity can be resonated, if the power that is delivered to the cavity propagated with very low losses, and if power can be extracted at other locations within the cavity. Experimental data collected and calculations made in recent years support the hypothesis that wireless power transmission is a viable and practical alternative to the present systems of power transmission

  13. Regional transmission subsystem planning

    Energy Technology Data Exchange (ETDEWEB)

    Costa Bortoni, Edson da [Quadrante Softwares Especializados Ltda., Itajuba, MG (Brazil); Bajay, Sergio Valdir; Barros Correia, Paulo de [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Engenharia Mecanica; Santos, Afonso Henriques Moreira; Haddad, Jamil [Escola Federal de Engenharia de Itajuba, MG (Brazil)

    1994-12-31

    This work presents an approach for the planning of transmission systems by employing mixed--integer linear programming to obtain a cost and operating characteristics optimized system. The voltage loop equations are written in a modified form, so that, at the end of the analysis, the model behaves as a DC power flow, with the help of the two Kirchhoff`s laws, exempting the need of interaction with an external power flow program for analysis of the line loading. The model considers the occurrence of contingencies, so that the final result is a network robust to the most severe contingencies. This whole technique is adapted to the regional electric power transmission subsystems. (author) 9 refs., 4 figs.

  14. Available transmission capacity assessment

    Directory of Open Access Journals (Sweden)

    Škokljev Ivan

    2012-01-01

    Full Text Available Effective power system operation requires the analysis of vast amounts of information. Power market activities expose power transmission networks to high-level power transactions that threaten normal, secure operation of the power system. When there are service requests for a specific sink/source pair in a transmission system, the transmission system operator (TSO must allocate the available transfer capacity (ATC. It is common that ATC has a single numerical value. Additionally, the ATC must be calculated for the base case configuration of the system, while generation dispatch and topology remain unchanged during the calculation. Posting ATC on the internet should benefit prospective users by aiding them in formulating their requests. However, a single numerical value of ATC offers little for prospect for analysis, planning, what-if combinations, etc. A symbolic approach to the power flow problem (DC power flow and ATC offers a numerical computation at the very end, whilst the calculation beforehand is performed by using symbols for the general topology of the electrical network. Qualitative analysis of the ATC using only qualitative values, such as increase, decrease or no change, offers some new insights into ATC evaluation, multiple transactions evaluation, value of counter-flows and their impact etc. Symbolic analysis in this paper is performed after the execution of the linear, symbolic DC power flow. As control variables, the mathematical model comprises linear security constraints, ATC, PTDFs and transactions. The aim is to perform an ATC sensitivity study on a five nodes/seven lines transmission network, used for zonal market activities tests. A relatively complicated environment with twenty possible bilateral transactions is observed.

  15. Dynamic Strategic Information Transmission

    OpenAIRE

    Mikhail Golosov; Vasiliki Skreta; Aleh Tsyvinski; Andrea Wilson

    2011-01-01

    This paper studies strategic information transmission in a dynamic environment where, each period, a privately informed expert sends a message and a decision maker takes an action. Our main result is that, in contrast to a static environment, full information revelation is possible. The gradual revelation of information and the eventual full revelation is supported by the dynamic rewards and punishments. The construction of a fully revealing equilibrium relies on two key features. The first f...

  16. Operational electricity transmission rates

    International Nuclear Information System (INIS)

    Roggen, M.

    1997-01-01

    In a liberalized electricity market both the consumers and the producers of electricity must pay for the use of the power transmission network. Thus, the net manager has unlimited options to realize efficiency improvements. A neutral and transparent management of the power grid is necessary to avoid disturbance of the market. KEMA Consulting translated abstract ideas and strategic advices to operational concepts in its report 'A framework for the determination of tariffs of the transport in the Dutch electricity sector'

  17. [Mumps vaccine virus transmission].

    Science.gov (United States)

    Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

    2013-01-01

    In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

  18. Small passenger car transmission test; Chevrolet LUV transmission

    Science.gov (United States)

    Bujold, M. P.

    1980-01-01

    A 1978 Chevrolet LUV manual transmission tested per the applicable portions of a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the upper ninety percent range for both drive performance tests and coast performance tests. The major results of this test (torque, speed, and efficiency curves) are presented. Graphs map the complete performance characteristics for the Chevrolet LUV transmission.

  19. Benefits of transmission interconnections

    International Nuclear Information System (INIS)

    Lyons, D.

    2006-01-01

    The benefits of new power transmission interconnections from Alberta were discussed with reference to the challenges and measures needed to move forward. Alberta's electricity system has had a long period of sustained growth in generation and demand and this trend is expected to continue. However, no new interconnections have been built since 1985 because the transmission network has not expanded in consequence with the growth in demand. As such, Alberta remains weakly interconnected with the rest of the western region. The benefits of stronger transmission interconnections include improved reliability, long-term generation capability, hydrothermal synergies, a more competitive market, system efficiencies and fuel diversity. It was noted that the more difficult challenges are not technical. Rather, the difficult challenges lie in finding an appropriate business model that recognizes different market structures. It was emphasized that additional interconnections are worthwhile and will require significant collaboration among market participants and governments. It was concluded that interties enable resource optimization between systems and their benefits far exceed their costs. tabs., figs

  20. On the use of information theory for the analysis of synchronous nociceptive withdrawal reflexes and somatosensory evoked potentials elicited by graded electrical stimulation.

    Science.gov (United States)

    Arguissain, Federico G; Biurrun Manresa, José A; Mørch, Carsten D; Andersen, Ole K

    2015-01-30

    To date, few studies have combined the simultaneous acquisition of nociceptive withdrawal reflexes (NWR) and somatosensory evoked potentials (SEPs). In fact, it is unknown whether the combination of these two signals acquired simultaneously could provide additional information on somatosensory processing at spinal and supraspinal level compared to individual NWR and SEP signals. By using the concept of mutual information (MI), it is possible to quantify the relation between electrical stimuli and simultaneous elicited electrophysiological responses in humans based on the estimated stimulus-response signal probability distributions. All selected features from NWR and SEPs were informative in regard to the stimulus when considered individually. Specifically, the information carried by NWR features was significantly higher than the information contained in the SEP features (pinformation carried by the combination of features showed an overall redundancy compared to the sum of the individual contributions. Comparison with existing methods MI can be used to quantify the information that single-trial NWR and SEP features convey, as well as the information carried jointly by NWR and SEPs. This is a model-free approach that considers linear and non-linear correlations at any order and is not constrained by parametric assumptions. The current study introduces a novel approach that allows the quantification of the individual and joint information content of single-trial NWR and SEP features. This methodology could be used to decode and interpret spinal and supraspinal interaction in studies modulating the responsiveness of the nociceptive system. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870 on Mechanical Sensitivity in Diet-Induced Obesity Model

    Directory of Open Access Journals (Sweden)

    Fereshteh Dardmeh

    2016-01-01

    Full Text Available Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU of probiotics (Lactobacillus rhamnosus PB01, DSM14870 supplement on mechanical pain thresholds in behaving diet-induced obese (DIO mice and their normal weight (NW controls. The mice (N=24, 6-week-old male were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P<0.05. Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P<0.05 lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation.

  2. BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response to Thermal Stimulation of the Forepaws.

    Directory of Open Access Journals (Sweden)

    Simone C Bosshard

    Full Text Available Functional magnetic resonance imaging (fMRI in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers.

  3. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    Science.gov (United States)

    Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

  4. Pain and Nociception

    DEFF Research Database (Denmark)

    Falk, Sarah; Dickenson, Anthony H

    2014-01-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditiona...

  5. Alternative approaches to transmission investment

    Energy Technology Data Exchange (ETDEWEB)

    Welch, J.L. [International Transmission Co., Detroit, MI (United States)

    2004-07-01

    The International Transmission Company (ITC) is an independent power transmission company that owns, operates and maintains the high voltage transmission system in southeastern Michigan. The company's current focus is on investing in the transmission infrastructure to improve reliability, relieve congestion, improve access to generation and reduce energy costs for consumers. There is a need for investment in power transmission. Trends indicate that power transactions are on the rise while transmission investment is lagging because pricing protocols are inadequate and there is no regional tariff mechanism to allocate the benefits of new investment. The presentation reviewed the applicability of FTRs to transmission owners and the pitfalls of participant funding pricing. It also outlined the regional benefit allocation mechanism (RBAM) with an illustrative example. It was concluded that existing pricing policies must be improved to address the growing need for transmission investment. RBAM is needed to help investors recover costs from project beneficiaries. figs.

  6. Our views on transmission policy

    International Nuclear Information System (INIS)

    Wellford, W.H.; Sutley, N.H.

    1990-01-01

    In this article the authors discuss the need for predictable and fair access to transmission facilities in order to ensure competitive generation of power. They propose that the Federal Energy Regulatory Commission should regulate transmission to prevent a utility from gaining a competitive advantage in electricity generation markets, the incorporation of transmission access into every bidding program under state jurisdiction, and requirement of transmission rates, terms and conditions for all in-state utilities be included in the request for proposal

  7. Parallel plate transmission line transformer

    NARCIS (Netherlands)

    Voeten, S.J.; Brussaard, G.J.H.; Pemen, A.J.M.

    2011-01-01

    A Transmission Line Transformer (TLT) can be used to transform high-voltage nanosecond pulses. These transformers rely on the fact that the length of the pulse is shorter than the transmission lines used. This allows connecting the transmission lines in parallel at the input and in series at the

  8. Planetary Transmission Diagnostics

    Science.gov (United States)

    Lewicki, David G. (Technical Monitor); Samuel, Paul D.; Conroy, Joseph K.; Pines, Darryll J.

    2004-01-01

    This report presents a methodology for detecting and diagnosing gear faults in the planetary stage of a helicopter transmission. This diagnostic technique is based on the constrained adaptive lifting algorithm. The lifting scheme, developed by Wim Sweldens of Bell Labs, is a time domain, prediction-error realization of the wavelet transform that allows for greater flexibility in the construction of wavelet bases. Classic lifting analyzes a given signal using wavelets derived from a single fundamental basis function. A number of researchers have proposed techniques for adding adaptivity to the lifting scheme, allowing the transform to choose from a set of fundamental bases the basis that best fits the signal. This characteristic is desirable for gear diagnostics as it allows the technique to tailor itself to a specific transmission by selecting a set of wavelets that best represent vibration signals obtained while the gearbox is operating under healthy-state conditions. However, constraints on certain basis characteristics are necessary to enhance the detection of local wave-form changes caused by certain types of gear damage. The proposed methodology analyzes individual tooth-mesh waveforms from a healthy-state gearbox vibration signal that was generated using the vibration separation (synchronous signal-averaging) algorithm. Each waveform is separated into analysis domains using zeros of its slope and curvature. The bases selected in each analysis domain are chosen to minimize the prediction error, and constrained to have the same-sign local slope and curvature as the original signal. The resulting set of bases is used to analyze future-state vibration signals and the lifting prediction error is inspected. The constraints allow the transform to effectively adapt to global amplitude changes, yielding small prediction errors. However, local wave-form changes associated with certain types of gear damage are poorly adapted, causing a significant change in the

  9. Coaxial transmission line - Equalization

    International Nuclear Information System (INIS)

    Bonnerue, J.L.; Fremont, Jacques; Haubtmann, Jack; Pillon, Gerard.

    1981-09-01

    The transmission of electrical signal through a coaxial line is not perfect and signal distortions are increased as much as the frequency spectrum is extended. We have designed and achieved passive filters (named equalizers) with transfer functions which are inverse of coaxial transfer functions. Doing so our attempt is to avoid definitive loss of information in the recorded data. The main feature of our equalization method lies in the fact it could be either an electrical or a numerical correction or both of them. Some examples in the use of this technique are also proposed [fr

  10. Dynamically prioritized progressive transmission

    Science.gov (United States)

    Blanford, Ronald

    1992-04-01

    Retrieval of image data from a centralized database may be subject to bandwidth limitations, whether due to a low-bandwidth communications link or to contention from simultaneous accesses over a high-bandwidth link. Progressive transmission can alleviate this problem by encoding image data so that any prefix of the data stream approximates the complete image at a coarse level of resolution. The longer the prefix, the finer the resolution. In many cases, as little at 1 percent of the image data may be sufficient to decide whether to discard the image, to permit the retrieval to continue, or to restrict retrieval to a subsection of the image. Our approach treats resolution not as a fixed attribute of the image, but rather as a resource which may be allocated to portions of the image at the direction of a user-specified priority function. The default priority function minimizes error by allocating more resolution to regions of high variance. The user may also point to regions of interest requesting priority transmission. More advanced target recognition strategies may be incorporated at the user's discretion. Multispectral imagery is supported. The user engineering implications are profounded. There is immediate response to a query that might otherwise take minutes to complete. The data is transmitted in small increments so that no single user dominates the communications bandwidth. The user-directed improvement means that bandwidth is focused on interesting information. The user may continue working with the first coarse approximations while further image data is still arriving. The algorithm has been implemented in C on Sun, Silicon Graphics, and NeXT workstations, and in Lisp on a Symbolics. Transmission speeds reach as high as 60,000 baud using a Sparc or 68040 processor when storing data to memory; somewhat less if also updating a graphical display. The memory requirements are roughly five bytes per image pixel. Both computational and memory costs may be reduced

  11. Research and Transmission

    Directory of Open Access Journals (Sweden)

    Denise Pumain

    2001-01-01

    Full Text Available The present situation provides a challenge for us to reconsider the necessary link between science and pedagogy, between research and the transmission of knowledge. The Ministry of National education has just inaugurated a broad consultation of teachers on every level with a view to modernising and giving coherence to the programs of secondary education. Armand Frémont will head the group of experts responsible for history and geography. Is this a coincidence? The changeover in the jury for t...

  12. Economy of electric power transmission

    International Nuclear Information System (INIS)

    Manzoni, G.; Delfanti, M.

    2008-01-01

    An analysis is presented of the impact of H V and Ehv transmission costs on the final value of the kWh supplied, with reference both to transmission systems of the European type and to long distance point-to-point transmission links. The analysis is extended to A C transmission by underground cables and to Hvdc submarine and aerial links. In the European power system, the impact of transmission costs results to be usually modest, but it may become important in the case of network congestions [it

  13. The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

    Science.gov (United States)

    Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

    2016-04-01

    It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Small passenger car transmission test-Chevrolet 200 transmission

    Science.gov (United States)

    Bujold, M. P.

    1980-01-01

    The small passenger car transmission was tested to supply electric vehicle manufacturers with technical information regarding the performance of commerically available transmissions which would enable them to design a more energy efficient vehicle. With this information the manufacturers could estimate vehicle driving range as well as speed and torque requirements for specific road load performance characteristics. A 1979 Chevrolet Model 200 automatic transmission was tested per a passenger car automatic transmission test code (SAE J651b) which required drive performance, coast performance, and no load test conditions. The transmission attained maximum efficiencies in the mid-eighty percent range for both drive performance tests and coast performance tests. Torque, speed and efficiency curves map the complete performance characteristics for Chevrolet Model 200 transmission.

  15. Transmission rights and market power

    International Nuclear Information System (INIS)

    Bushnell, J.

    1999-01-01

    Most of the concerns about physical transmission rights relate to the ability to implicitly or explicitly remove that transmission capacity from the market-place. Under a very strict form of physical right, owners could simply choose not to sell it if they don't want to use it. Modifications that require the release of spare capacity back into an open market could potentially alleviate this problem but there is concern that such releases would not occur far enough in advance to be of much use to schedulers. Similarly, the transmission capacity that is made available for use by non-rights holders can also be manipulated by the owners of transmission rights. The alternative form, financial transmission rights, provide to their owners congestion payments, but physical control of transmission paths. In electricity markets such as California's, even financial transmission rights could potentially be utilized to effectively withhold transmission capacity from the marketplace. However, methods for withholding transmission capacity are somewhat more convoluted, and probably more difficult, for owners of financial rights than for owners of physical rights. In this article, the author discusses some of the potential concerns over transmission rights and their use for the exercise of various forms of market power

  16. Stress transmission in soil

    DEFF Research Database (Denmark)

    Lamandé, Mathieu; Schjønning, Per

    We urgently need increased quantitative knowledge on stress transmission in real soils loaded with agricultural machinery. 3D measurements of vertical stresses under tracked wheels were performed in situ in a Stagnic Luvisol (clay content 20 %) continuously cropped with small grain cereals......). Seven load cells were inserted horizontally from a pit with minimal disturbance of soil in each of three depths (0.3, 0.6 and 0.9 m), covering the width of the wheeled area. The position of the wheel relative to the transducers was recorded using a laser sensor. Finally, the vertical stresses near...... the soil-tyre interface were measured in separate tests by 17 stress transducers across the width of the tyres. The results showed that the inflation pressure controlled the level of maximum stresses at 0.3 m depth, while the wheel load was correlated to the measured stresses at 0.9 m depth. This supports...

  17. Information transmission strategy

    International Nuclear Information System (INIS)

    Moreau, A.

    1989-01-01

    The four propositions on which our radiation protection information transmission strategy is based are as follows: 1. Emotion exists. It rules our lives at work as well as at home, particularly when radiation safety is involved. Emotion is therefore the terrain for our strategy. 2. The basic emotion is that of fear. This must be recognized and accepted if we want to transmit objective information. The basis of our strategy is therefore listening. 3. A person cannot be divided into parts. The whole person is concerned about safety. We have to deal with that whole person. 4. To follow a strategy we need strategists. We must look at our own emotions and our own motivation before going into the field

  18. Underground transmission tomography

    International Nuclear Information System (INIS)

    Geibka, C.

    1990-01-01

    Several underground tomographic transmission surveys have been carried out. Targets were cavities, ore veins and fault zones. Examples from measurements in a german heavy/fluor spar mine a lead/zinc mine and a rock laboratory of the Swiss National Cooperative for the Storage of Radioactive waste are presented. Measurements were carried out between boreholes and road ways. The recording equipment was the intrinsically safe SEAMEX85 system built and sold by WBK. Receivers were mounted in a chain of 6 two-component probes. Sources were an inhole hammer a sledge hammer a sparker and explosives from a single detonator to 180 g depending on the distance and absorption of the rock material. Cavities showed very distinct velocity reductions between 30 and 50%. Different vein material showed velocity reduction as well as velocity increase relative to the surrounding rock

  19. Evaluation of anti-nociceptive and anti-inflammatory activities of hydroalcoholic extract derived from root of Apium graveolens L. in mice

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Apium graveolens L. (celery has been considered as sedative, analgesic, carminative, antispasmodic and diuretic plant in traditional Iranian medicine. The aim of the present study was to evaluate the anti-nociceptive and anti-inflammatory effect of celery root in mice. Methods: Analgesic effect of celery root was determined by two animal models of hot plate and acetic acid writhing test. Anti-inflammatory potential of the extract was also determined by formalin induced ear edema and xylene induced paw edema tests.  Results: The result showed no significant difference between the positive control group and the test group in hot plate test and the most effective dose of celery root was 200 mg/kg, while the frequency of writhings was significantly different in whole test groups in comparison with control group (p

  20. Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: their anti-inflammatory and anti-nociceptive activities.

    Science.gov (United States)

    Shafi, Syed; Alam, Mohammad Mahboob; Mulakayala, Naveen; Mulakayala, Chaitanya; Vanaja, G; Kalle, Arunasree M; Pallu, Reddanna; Alam, M S

    2012-03-01

    A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  1. Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms and signs of nociceptive pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'nociceptive pain\\' (NP) refers to pain attributable to the activation of the peripheral receptive terminals of primary afferent neurones in response to noxious chemical, mechanical or thermal stimuli. The symptoms and signs associated with clinical classifications of NP have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of NP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol after which their pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various symptoms and signs. A regression analysis identified a cluster of seven clinical criteria predictive of NP, including: \\'Pain localised to the area of injury\\/dysfunction\\

  2. Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol.

    Science.gov (United States)

    Naziroğlu, Mustafa; Ozgül, Cemil

    2012-02-01

    Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05) on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca(2+) gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons.

  3. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

    Science.gov (United States)

    Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

    2017-04-01

    Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.

  4. Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat.

    Science.gov (United States)

    Martin, Mario; Béjar, Javier; Esposito, Gennaro; Chávez, Diógenes; Contreras-Hernández, Enrique; Glusman, Silvio; Cortés, Ulises; Rudomín, Pablo

    2017-01-01

    In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials ( CDPs ). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs . We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive stimulation. They

  5. Transmission diamond imaging detector

    Energy Technology Data Exchange (ETDEWEB)

    Smedley, John, E-mail: smedley@bnl.gov; Pinelli, Don; Gaoweia, Mengjia [Brookhaven National Laboratory, Upton, NY (United States); Muller, Erik; Ding, Wenxiang; Zhou, Tianyi [Stony Brook University, Stony Brook, NY (United States); Bohon, Jen [Case Center for Synchrotron Biosciences, Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH (United States)

    2016-07-27

    Many modern synchrotron techniques are trending toward use of high flux beams and/or beams which require enhanced stability and precise understanding of beam position and intensity from the front end of the beamline all the way to the sample. For high flux beams, major challenges include heat load management in optics (including the vacuum windows) and a mechanism of real-time volumetric measurement of beam properties such as flux, position, and morphology. For beam stability in these environments, feedback from such measurements directly to control systems for optical elements or to sample positioning stages would be invaluable. To address these challenges, we are developing diamond-based instrumented vacuum windows with integrated volumetric x-ray intensity, beam profile and beam-position monitoring capabilities. A 50 µm thick single crystal diamond has been lithographically patterned to produce 60 µm pixels, creating a >1kilopixel free-standing transmission imaging detector. This device, coupled with a custom, FPGA-based readout, has been used to image both white and monochromatic x-ray beams and capture the last x-ray photons at the National Synchrotron Light Source (NSLS). This technology will form the basis for the instrumented end-station window of the x-ray footprinting beamline (XFP) at NSLS-II.

  6. Control of schistosomiasis transmission

    Directory of Open Access Journals (Sweden)

    Luiz C. de S. Dias

    1995-04-01

    Full Text Available Despite the success of control programmes, schistosomiasis is still a serious public health problem in the world. More than 70 countries where 200 million individuals are evaluated to be infected of a total 600 million at risk. Though there have been important local success in the control of transmission, globally the infection has increased. Economic constrains in developing countries, environmental changes associated with migration and water resources development have been blocking the progress. The main objective of schistosomiasis control is to achieve reduction of disease due to schistosomiasis. We discussed the control measures like: health education, diagnosis and chemotherapy, safe water supplies, sanitation and snail control. We emphasized the need to give priority to school-age children and the importance of integrating the measures of control into locally available systems of health care. The control of schistosomiasis is directly related to the capacity of the preventive health services of an endemic country. The strategy of control requires long-term commitment from the international to the local level.

  7. Transmission acoustic microscopy investigation

    Science.gov (United States)

    Maev, Roman; Kolosov, Oleg; Levin, Vadim; Lobkis, Oleg

    The nature of acoustic contrast, i.e. the connection of the amplitude and phase of the output signal of the acoustic microscope with the local values of the acoustic parameters of the sample (density, elasticity, viscosity) is a central problem of acoustic microscopy. A considerable number of studies have been devoted to the formation of the output signal of the reflection scanning acoustic microscope. For the transmission acoustic microscope (TAM) this problem has remained almost unstudied. Experimental investigation of the confocal system of the TAM was carried out on an independently manufactured laboratory mockup of the TAM with the working frequency of the 420 MHz. Acoustic lenses with the radius of curvature of about 500 microns and aperture angle of 45 deg were polished out in the end faces of two cylindrical sound conductors made from Al2O3 single crystals with an axis parallel to the axis C of the crystal (the length of the sound conductor is 20 mm; diameter, 6 mm). At the end faces of the sound conductor, opposite to the lenses, CdS transducers with a diameter of 2 mm were disposed. The electric channel of the TAM provided a possibility for registering the amplitude of the microscope output signal in the case of the dynamic range of the 50 dB.

  8. HVDC power transmission technology assessment

    Energy Technology Data Exchange (ETDEWEB)

    Hauth, R.L.; Tatro, P.J.; Railing, B.D. [New England Power Service Co., Westborough, MA (United States); Johnson, B.K.; Stewart, J.R. [Power Technologies, Inc., Schenectady, NY (United States); Fink, J.L.

    1997-04-01

    The purpose of this study was to develop an assessment of the national utility system`s needs for electric transmission during the period 1995-2020 that could be met by future reduced-cost HVDC systems. The assessment was to include an economic evaluation of HVDC as a means for meeting those needs as well as a comparison with competing technologies such as ac transmission with and without Flexible AC Transmission System (FACTS) controllers. The role of force commutated dc converters was to be assumed where appropriate. The assessment begins by identifying the general needs for transmission in the U.S. in the context of a future deregulated power industry. The possible roles for direct current transmission are then postulated in terms of representative scenarios. A few of the scenarios are illustrated with the help of actual U.S. system examples. non-traditional applications as well as traditional applications such as long lines and asynchronous interconnections are discussed. The classical ``break-even distance`` concept for comparing HVDC and ac lines is used to assess the selected scenarios. The impact of reduced-cost converters is reflected in terms of the break-even distance. This report presents a comprehensive review of the functional benefits of HVDC transmission and updated cost data for both ac and dc system components. It also provides some provocative thoughts on how direct current transmission might be applied to better utilize and expand our nation`s increasingly stressed transmission assets.

  9. Endoscopic transmission of Helicobacter pylori

    NARCIS (Netherlands)

    Tytgat, G. N.

    1995-01-01

    The contamination of endoscopes and biopsy forceps with Helicobacter pylori occurs readily after endoscopic examination of H. pylori-positive patients. Unequivocal proof of iatrogenic transmission of the organism has been provided. Estimates for transmission frequency approximate to 4 per 1000

  10. Transmission reliability faces future challenges

    International Nuclear Information System (INIS)

    Beaty, W.

    1993-01-01

    The recently published Washington International Energy Group's 1993 Electric Utility Outlook states that nearly one-third (31 percent) of U.S. utility executives expect reliability to decrease in the near future. Electric power system stability is crucial to reliability. Stability analysis determines whether a system will stay intact under normal operating conditions, during minor disturbances such as load fluctuations, and during major disturbances when one or more parts of the system fails. All system elements contribute to reliability or the lack of it. However, this report centers on the transmission segment of the electric system. The North American Electric Reliability Council (NERC) says the transmission systems as planned will be adequate over the next 10 years. However, delays in building new lines and increasing demands for transmission services are serious concerns. Reliability concerns exist in the Mid-Continent Area Power Pool and the Mid-America Interconnected Network regions where transmission facilities have not been allowed to be constructed as planned. Portions of the transmission systems in other regions are loaded at or near their limits. NERC further states that utilities must be allowed to complete planned generation and transmission as scheduled. A reliable supply of electricity also depends on adhering to established operating criteria. Factors that could complicate operations include: More interchange schedules resulting from increased transmission services. Increased line loadings in portions of the transmission systems. Proliferation of non-utility generators

  11. Energy Transmission and Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Mathison, Jane

    2012-12-31

    The objective of Energy Transmission and Infrastructure Northern Ohio (OH) was to lay the conceptual and analytical foundation for an energy economy in northern Ohio that will: • improve the efficiency with which energy is used in the residential, commercial, industrial, agricultural, and transportation sectors for Oberlin, Ohio as a district-wide model for Congressional District OH-09; • identify the potential to deploy wind and solar technologies and the most effective configuration for the regional energy system (i.e., the ratio of distributed or centralized power generation); • analyze the potential within the district to utilize farm wastes to produce biofuels; • enhance long-term energy security by identifying ways to deploy local resources and building Ohio-based enterprises; • identify the policy, regulatory, and financial barriers impeding development of a new energy system; and • improve energy infrastructure within Congressional District OH-09. This objective of laying the foundation for a renewable energy system in Ohio was achieved through four primary areas of activity: 1. district-wide energy infrastructure assessments and alternative-energy transmission studies; 2. energy infrastructure improvement projects undertaken by American Municipal Power (AMP) affiliates in the northern Ohio communities of Elmore, Oak Harbor, and Wellington; 3. Oberlin, OH-area energy assessment initiatives; and 4. a district-wide conference held in September 2011 to disseminate year-one findings. The grant supported 17 research studies by leading energy, policy, and financial specialists, including studies on: current energy use in the district and the Oberlin area; regional potential for energy generation from renewable sources such as solar power, wind, and farm-waste; energy and transportation strategies for transitioning the City of Oberlin entirely to renewable resources and considering pedestrians, bicyclists, and public transportation as well as drivers

  12. Regional Transmission Projects: Finding Solutions

    Energy Technology Data Exchange (ETDEWEB)

    The Keystone Center

    2005-06-15

    The Keystone Center convened and facilitated a year-long Dialogue on "Regional Transmission Projects: Finding Solutions" to develop recommendations that will help address the difficult and contentious issues related to expansions of regional electric transmission systems that are needed for reliable and economic transmission of power within and across regions. This effort brought together a cross-section of affected stakeholders and thought leaders to address the problem with the collective wisdom of their experience and interests. Transmission owners sat at the table with consumer advocates and environmental organizations. Representatives from regional transmission organizations exchanged ideas with state and federal regulators. Generation developers explored common interests with public power suppliers. Together, the Dialogue participants developed consensus solutions about how to begin unraveling some of the more intractable issues surrounding identification of need, allocation of costs, and reaching consensus on siting issues that can frustrate the development of regional transmission infrastructure. The recommendations fall into three broad categories: 1. Recommendations on appropriate institutional arrangements and processes for achieving regional consensus on the need for new or expanded transmission infrastructure 2. Recommendations on the process for siting of transmission lines 3. Recommendations on the tools needed to support regional planning, cost allocation, and siting efforts. List of Dialogue participants: List of Dialogue Participants: American Electric Power American Transmission Company American Wind Energy Association California ISO Calpine Corporation Cinergy Edison Electric Institute Environmental Defense Federal Energy Regulatory Commission Great River Energy International Transmission Company ISO-New England Iowa Public Utility Board Kanner & Associates Midwest ISO National Association of Regulatory Utility Commissioners National Association

  13. The evolution of transmission mode

    Science.gov (United States)

    Forbes, Mark R.; Hauffe, Heidi C.; Kallio, Eva R.; Okamura, Beth; Sait, Steven M.

    2017-01-01

    This article reviews research on the evolutionary mechanisms leading to different transmission modes. Such modes are often under genetic control of the host or the pathogen, and often in conflict with each other via trade-offs. Transmission modes may vary among pathogen strains and among host populations. Evolutionary changes in transmission mode have been inferred through experimental and phylogenetic studies, including changes in transmission associated with host shifts and with evolution of the unusually complex life cycles of many parasites. Understanding the forces that determine the evolution of particular transmission modes presents a fascinating medley of problems for which there is a lack of good data and often a lack of conceptual understanding or appropriate methodologies. Our best information comes from studies that have been focused on the vertical versus horizontal transmission dichotomy. With other kinds of transitions, theoretical approaches combining epidemiology and population genetics are providing guidelines for determining when and how rapidly new transmission modes may evolve, but these are still in need of empirical investigation and application to particular cases. Obtaining such knowledge is a matter of urgency in relation to extant disease threats. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’. PMID:28289251

  14. Alternative approaches to transmission investment

    Energy Technology Data Exchange (ETDEWEB)

    Thon, S. [AltaLink Management Ltd., Calgary, AB (Canada)

    2004-07-01

    AltaLink is Canada's first stand-alone power transmission company, serving all major centres in Alberta and 85 per cent of Alberta's population. It has more than $1 billion in assets, 11,500 km of transmission lines and 300 substations. It was noted that there has not been any significant investment in power transmission in Alberta for the past 20 years, partly because transmission assets have a very long lifespan. The new role of the power grid is to ensure reliability, safety, efficiency, market effectiveness and supply diversity. The benefits and costs of AltaLink's 500 kV North-South upgrade project were outlined. It was noted that a healthy transmission system is the basis for economic growth throughout the province and for the development of Alberta's resource base. The transmission policy in Alberta endorses that all consumers pay postage stamp tariffs. It also promotes a proactive plan for transmission projects, the time to maximum rate (TMR) in limited cases only, a congestion-free grid under normal conditions, the financial commitment of generators, specific time limits on permitting processes, and regional interconnections to benefit all customers. tabs., figs.

  15. Transmission Line Series Compensation for Wind Energy Transmission

    International Nuclear Information System (INIS)

    Palanichamy, C; Wong, Y C

    2015-01-01

    Wind energy has demonstrated to be a clean, copious and absolutely renewable source of energy, and the large penetration of it into the power grid indicates that wind energy is considered an effective means of power generation, Transmission of wind energy from remote locations to load centers necessitates long transmission lines. Series compensation is a proven and economical transmission solution to address system power transfer strength, grid stability, and voltage profile issues of long transmission lines. In this paper, a programmable approach to determine the capacitive reactance of series capacitor and optimum location for its placement to achieve maximum power transfer gas been presented. The respective program with sample solutions has been provided for real-time applications. (paper)

  16. Midwest Transmission Workshop I Summary

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Bryan

    2001-05-01

    OAK-B135 The meeting was opened with a review of the purposes of the workshop: (1) Present and discuss key studies and assessments of transmission upgrades, additions and related issues for the upper Midwest, including work that addresses the full range of views on these topics; (2) Understand the various transmission issues in the upper Midwest and discuss options for addressing the issues; and (3) Identify the decision makers and entities that need to play an active role if transmission issues are to be resolved, and agree on next steps for engaging these individuals and organizations through education, outreach, and information dissemination.

  17. Markets for financial transmission rights

    International Nuclear Information System (INIS)

    Kristiansen, T.

    2004-01-01

    Results of a survey of markets for financial transmission rights that facilitate competitive, open and non-discriminatory electricity market design are discussed. Specifically, the survey covered Pennsylvania, New Jersey, Maryland (PJM), New York, California, New England, Texas and New Zealand. The main emphasis was on the PJM and the New York markets, since they are the most mature. Interwowen with the results is a thorough discussion of the properties, features and the design of financial transaction rights in the various jurisdictions, the advantages, disadvantages and market performance of financial transmission rights, market performance criteria, and the mechanism for acquiring financial transmission rights. 49 refs., 14 tabs., 6 figs

  18. Transmission eigenvalues and thermoacoustic tomography

    International Nuclear Information System (INIS)

    Finch, David; Hickmann, Kyle S

    2013-01-01

    The spectrum of the interior transmission problem is related to the unique determination of the acoustic properties of a body in thermoacoustic imaging. Under a non-trapping hypothesis, we show that sparsity of the interior transmission spectrum implies a range separation condition for the thermoacoustic operator. In odd dimensions greater than or equal to 3, we prove that the interior transmission spectrum for a pair of radially symmetric non-trapping sound speeds is countable, and conclude that the ranges of the associated thermoacoustic maps have only trivial intersection. (paper)

  19. The evolution of plant virus transmission pathways

    Science.gov (United States)

    Frédéric M. Hamelin; Linda J.S. Allen; Holly R. Prendeville; M. Reza Hajimorad; Michael J. Jeger

    2016-01-01

    The evolution of plant virus transmission pathways is studied through transmission via seed, pollen, oravector. We address the questions: under what circumstances does vector transmission make pollen transmission redundant? Can evolution lead to the coexistence of multiple virus transmission pathways? We restrict the analysis to an annual plant population in which...

  20. Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat

    Directory of Open Access Journals (Sweden)

    Mario Martin

    2017-05-01

    Full Text Available In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials (CDPs. This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs. We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive

  1. Handheld mechanical nociceptive threshold testing in dairy cows – intra-individual variation, inter-observer agreement and variation over time

    Science.gov (United States)

    Raundal, Peter M; Andersen, Pia H; Toft, Nils; Forkman, Björn; Munksgaard, Lene; Herskin, Mette S

    2014-01-01

    Objective To examine the use of handheld methodology to assess mechanical nociceptive threshold (MNT) on cows kept loose-housed. Study design Prospective randomized partial cross-over experimental study. A one-factor (test day) design was used to evaluate MNT over time. Animals One hundred and fifteen healthy, loose-housed Danish Holstein cattle. Methods We evaluated intra-individual variation, inter-observer agreement and variation over time of MNT using two handheld devices and two stimulation sites. Mechanical, ramped stimulations were performed with an algometer (6.5 mm diameter steel probe, 0–10.0 kgf) or an electronic von Frey device (plastic tip with diameter 0.8 mm, 0–1000 gf). Each cow received 5–6 consecutive stimulations within a 2 × 5 cm skin area on the dorsal or lateral aspect of the left third metatarsus until an avoidance reaction occurred. We investigated the difference in precision [expressed as coefficient of variation (CV)] between the combinations of devices and stimulation sites. The inter-observer agreement and the difference in MNT between test day 1, 3, 7, 10 and 24 were investigated for selected combinations. Data were analysed in mixed models and Bland-Altman as relevant. Results The CVs did not differ [range 0.34–0.52 (p = 0.1)]. Difference between observers (95% limits) was 0.2 kgf (2.8) and 4 gf (369) for the algometer and von Frey device, respectively. Mechanical nociceptive threshold increased from 361 on test day one to 495 gf on test day 24 (p < 0.01). Conclusion and clinical relevance All methods showed a high degree of intra-individual variation, and no combination of device and stimulation site showed superior precision. Mean difference between observers was low, and MNT was not consistent over time. Further development of the methods is required before they can be used in research to investigate possible relations between claw lesions and hyperalgesia. PMID:24734991

  2. Echinococcosis : disease, detection and transmission

    NARCIS (Netherlands)

    Craig, P.S.; Rogan, M T; Campos-Ponce, M

    2003-01-01

    Echinococcosis is one of the world's most geographically widespread parasitic zoonoses, with transmission occurring in tropical, temperate and arctic biomes. Most human infections are due to Echinococcus granulosus transmitted between domestic dogs and livestock, but this cosmopolitan species also

  3. Hybrid-Vehicle Transmission System

    Science.gov (United States)

    Lupo, G.; Dotti, G.

    1985-01-01

    Continuously-variable transmission system for hybrid vehicles couples internal-combustion engine and electric motor section, either individually or in parallel, to power vehicle wheels during steering and braking.

  4. Accounting-related transmission issues

    International Nuclear Information System (INIS)

    Niehaus, M.; Bjorn, P.; Pate, G.

    1999-01-01

    Various initiatives have been undertaken by the Federal Energy Regulatory Commission (FERC) to deregulate wholesale electric energy markets. These initiatives have focused on restructuring the transmission systems in the US and recently have culminated in a proposal requiring formation of and participation in regional transmission organizations. The overall form of regulation selected to determine rates for transmission entities as well as underlying regulatory decisions reached on key issues will have profound implications for transmission entities. For example, traditional cost-based regulation would require one set of accounting and reporting rules, while incentive-based regulation may not be subject to those same rules. An overview of some of the major accounting and financial reporting issues that will need to be considered is presented

  5. Transmission of Information: An Overview.

    Science.gov (United States)

    Thoma, George R.

    1981-01-01

    Outlines the basic principles underlying the transmission of information, including analog and digital modulation, limitations to communications, configurations of communications networks, optical fiber cables, and earth satellites. Six references are cited. (FM)

  6. The nociceptive withdrawal reflex does not adapt to joint position change and short-term motor practice [v2; ref status: indexed, http://f1000r.es/2lr

    Directory of Open Access Journals (Sweden)

    Nathan Eckert

    2013-12-01

    Full Text Available The nociceptive withdrawal reflex is a protective mechanism to mediate interactions within a potentially dangerous environment. The reflex is formed by action-based sensory encoding during the early post-natal developmental period, and it is unknown if the protective motor function of the nociceptive withdrawal reflex in the human upper-limb is adaptable based on the configuration of the arm or if it can be modified by short-term practice of a similar or opposing motor action. In the present study, nociceptive withdrawal reflexes were evoked by a brief train of electrical stimuli applied to digit II, 1 in five different static arm positions and, 2 before and after motor practice that was opposite (EXT or similar (FLEX to the stereotyped withdrawal response, in 10 individuals. Withdrawal responses were quantified by the electromyography (EMG reflex response in several upper limb muscles, and by the forces and moments recorded at the wrist. EMG onset latencies and response amplitudes were not significantly different across the arm positions or between the EXT and FLEX practice conditions, and the general direction of the withdrawal response was similar across arm positions. In addition, the force vectors were not different after practice in either the practice condition or between EXT and FLEX conditions. We conclude the withdrawal response is insensitive to changes in elbow or shoulder joint angles as well as remaining resistant to short-term adaptations from the practice of motor actions, resulting in a generalized limb withdrawal in each case. It is further hypothesized that the multisensory feedback is weighted differently in each arm position, but integrated to achieve a similar withdrawal response to safeguard against erroneous motor responses that could cause further harm. The results remain consistent with the concept that nociceptive withdrawal reflexes are shaped through long-term and not short-term action based sensory encoding.

  7. Evidence of localized wave transmission

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    LLNL [Lawrence Livermore National Lab.] experiments to test the feasibility of launching an acoustic, directed-energy pulse train (ADEPT) in water have demonstrated localized transmission of wave energy far beyond the classical Rayleigh length that defines the boundary between near-field and far-field transmission for Gaussian (diffraction-limited) pulses. The results of the experiments are in excellent agreement with computer simulations

  8. Radio and line transmission 2

    CERN Document Server

    Roddy, Dermot

    2013-01-01

    Radio and Line Transmission, Volume 2 gives a detailed treatment of the subject as well as an introduction to additional advanced subject matter. Organized into 14 chapters, this book begins by explaining the radio wave propagation, signal frequencies, and bandwidth. Subsequent chapters describe the transmission lines and cables; the aerials; tuned and coupled circuits; bipolar transistor amplifiers; field-effect transistors and circuits; thermionic valve amplifiers; LC oscillators; the diode detectors and modulators; and the superheterodyne receiver. Other chapters explore noise and interfere

  9. Heartland Alliance for Regional Transmission

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Nancy [Climate and Energy Project, Inc., Hutchinson, KS (United States)

    2017-03-15

    The Heartland Alliance for Regional Transmission (HART) will foster a candid, productive conversation among stakeholders that identifies challenges to and benefits from a massive build out of wind generation and transmission across the Southwest Power Pool. Based on the outcomes of those deliberations, HART will develop and deliver an ambitious, coordinated, peer-to-peer outreach effort that spans the SPP to improve market acceptance for wind.

  10. Essays on electricity transmission investment and financial transmission rights

    Science.gov (United States)

    Shang, Wenzhuo

    The U.S. electric power industry has been going through fundamental restructuring and realignment since the 1990's. Many issues and problems have emerged during the transition, and both economists and engineers have been looking for the solutions fervently. In this dissertation, which consists primarily of three essays, we apply economics theory and techniques to the power industry and address two related issues, transmission investment and financial transmission rights (FTRs). The first essay takes the decentralized perspective and investigates the efficiency attribute of market-based transmission investment under perfect competition. We clarify, for the first time, the nature of the externality created by loop flows that causes transmission investment to be inefficient. Our findings have important implications for better understanding of transmission market design and creating incentives for efficient transmission investment. In the second essay, we define several rules for allocating transmission investment cost within the framework of cooperative game theory. These rules provide fair, stable or efficient cost allocations in theory and are good benchmarks against which the allocation mechanism in practice can be compared and improved upon. In the last essay, we make exploratory efforts in analyzing and assessing empirically the performance of the Midwest independent system operator (MISO) FTR auction market. We reveal some stylized facts about this young market and find that it is not efficient under the risk-neutrality assumption. We also point out and correct the drawbacks in previous related work and suggest about more complete empirical work in future. In all, this dissertation makes both theoretic and empirical analysis of the two hot issues related to the power industry and comes up with findings that have important implications for the development of this industry.

  11. Evaluating the merchant transmission market

    International Nuclear Information System (INIS)

    Hsieh, E.; Bartholomew Fisher, E.

    2007-01-01

    This paper reviewed the North American bulk electric transmission system, with particular reference to the following merchant power transmission projects that have applied to sell transmission at negotiated rates by the Federal Energy Regulatory Commission (FERC): Cross Sound Cable; Neptune Phase 1; TransCanada's Northern Lights HVDC line; Montana Alberta Tie; Juan de Fuca Cable; Linden VFT; Connecticut-Long Island Cable; Lake Erie Link; Empire Connection; Harbor Cable; Chesapeake Transmission; and the Neptune/Green Line. The projects were sorted by status as either active, inactive and restructured. Each summary included the interconnection points, capacity, and sponsor. This paper also identified the major hurdles in their approvals. The relative success of the merchant transmission framework in attracting new investment was then reviewed. The successful projects shared 3 common attributes. They connected areas with large price differentials and they used advanced flow control technology such as HVDC, PARs, and VFTs. The successful projects also bridged some type of border, either geographic, electrical, economic, or a combination. Three of the active projects crossed the Canadian-US border, while the other 3 connected New York City to neighbouring regions. It was shown that merchant transmission fills a niche, enabling market responses to connect areas that may be overlooked by a regional planning process. 27 refs

  12. Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors.

    Science.gov (United States)

    Li, Xiao-Qiu; Li, Man; Zhou, Zhong-He; Liu, Bao-Jun; Chen, Hui-Sheng

    2016-02-01

    Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

  13. Evaluation of anti-inflammatory, anti-nociceptive, and anti-arthritic activities of Indian Apis dorsata bee venom in experimental animals: biochemical, histological, and radiological assessment.

    Science.gov (United States)

    Nipate, S S; Hurali, Prakash B; Ghaisas, M M

    2015-04-01

    Traditionally venoms are used from thousands of years to treat pain, inflammation, and arthritis. In Ayurveda "Suchika Voron" and "Shodhona" were practiced against pain. In the present study, venom composition of the Indian honeybee Apis florea (AF), Apis dorsata (AD), and Apis cerana indica (AC) were analyzed using electrophoresis (SDS-PAGE). This venom analysis was used to shed light upon the correlation in structure and the venom composition among the three species in Indian fields. Among the three species, Indian Apis dorsata bee venom (ADBV) is evaluated for an anti-inflammatory, anti-nociceptive activity, and antiarthritic activity in different animal models. The effect of ADBV is revealed for its anti-arthritic activity in the FCA- and CIA-induced arthritis model in male Wistar rats. The immunosuppressant action of ADBV was studied by hemagglutination antibody titer. It has been found that ADBV possesses anti-inflammatory and antinociceptive activities. In FCA- and CIA-induced arthritis, ADBV able to decrease rheumatoid factor, pain perception parameters, C-reactive protein, erythrocytes sedimentation rate, urinary hydroxyproline, serum transaminase level, and serum nitric oxide level when compared with diseased control arthritic rats. IL-6, TNF-α level was found to be decrease by ADBV treatment in collagen induced arthritis model. Thus this study confirmed the scientific validation behind utilization of venom in Indian Apis dorsata bees in arthritis and inflammatory diseases which has been not reported till date.

  14. 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.

  15. Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

    Directory of Open Access Journals (Sweden)

    Heidi O Nousiainen

    Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

  16. Atlas transmission line breakdown analysis

    CERN Document Server

    Nielsen, K E; Ballard, E O; Elizondo, J M; Gribble, R F; McCuistian, B T; Parsons, W M

    1999-01-01

    The Atlas facility will use 24 radially converging, vertically oriented and tapered, oil insulated, triplate transmission lines between the Marx generators and the central load region. Among the requirements of the transmission lines are low inductance and high reliability. The inter-conductor gap is nominally 2 cm and the lines taper from a height of 1.75 m at the Marx end to 0.32 m at the output end. The aluminum conductors, held together by 20 insulating spacers, are assembled and inserted as a unit into radial oil-filled steel tanks. The negative, high-voltage, center conductor is 2.54-cm thick and the outer ground conductors are 1.59-cm thick. All 24 triplate transmission lines connect to a transition section at near 1 m radius that couples the transmission lines to a disk/conical solid- dielectric-insulated power flow channel transmission line terminating at the load. Peak operating voltage on the lines can be as high as 240 kV with an effective stress time of 0.8 mu s. Testing of small sections of the ...

  17. Plasmodium vivax Transmission in Africa.

    Directory of Open Access Journals (Sweden)

    Rosalind E Howes

    2015-11-01

    Full Text Available Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf. Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health

  18. Topics in lightwave transmission systems

    CERN Document Server

    Li, Tingye

    1991-01-01

    Topics in Lightwave Transmission Systems is a second volume of a treatise on optical fiber communications that is devoted to the science, engineering, and application of information transmission via optical fibers. The first volume, published in 1985, dealt exclusively with fiber fabrication. The present volume contains topics that pertain to subsystems and systems. The book contains five chapters and begins with discussions of transmitters and receivers, which are basic to systems now operating in the field. Subsequent chapters cover topics relating to coherent systems: frequency and phase m

  19. Transmission pricing: paradigms and methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)

    1994-12-31

    In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

  20. Money and transmission of bacteria.

    NARCIS (Netherlands)

    Gedik, H.; Voss, T.A.; Voss, A.

    2013-01-01

    Money is one of the most frequently passed items in the world. The aim of this study was to ascertain the survival status of bacteria including Staphylococcus aureus, Escherichia coli, and Vancomycin- Resistant Enterococci (VRE) on banknotes from different countries and the transmission of bacteria

  1. Solution of the Transmission Problem

    Czech Academy of Sciences Publication Activity Database

    Medková, Dagmar

    2010-01-01

    Roč. 110, č. 3 (2010), s. 1489-1500 ISSN 0167-8019 Institutional research plan: CEZ:AV0Z10190503 Keywords : Laplace equation * transmission problem * single layer potential * double layer potential Subject RIV: BA - General Mathematics Impact factor: 0.979, year: 2010 http://link.springer.com/article/10.1007%2Fs10440-009-9522-5

  2. Neutron Transmission through Sapphire Crystals

    DEFF Research Database (Denmark)

    of simulations, in order to reproduce the transmission of cold neutrons through sapphire crystals. Those simulations were part of the effort of validating and improving the newly developed interface between the Monte-Carlo neutron transport code MCNP and the Monte Carlo ray-tracing code McStas....

  3. Transmission electron microscopy of bone

    NARCIS (Netherlands)

    Everts, Vincent; Niehof, Anneke; Tigchelaar-Gutter, Wikky; Beertsen, Wouter

    2012-01-01

    This chapter describes procedures to process mineralized tissues obtained from different sources for transmission electron microscopy (TEM). Methods for fixation, resin embedding, staining of semi-thin sections and ultrathin sections are presented. In addition, attention will be paid to processing

  4. 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

  5. Effects of intraplantar botulinum toxin-B on carrageenan-induced changes in nociception and spinal phosphorylation of GluA1 and Akt.

    Science.gov (United States)

    Sikandar, Shafaq; Gustavsson, Ynette; Marino, Marc J; Dickenson, Anthony H; Yaksh, Tony L; Sorkin, Linda S; Ramachandran, Roshni

    2016-07-01

    Increasing evidence suggests that botulinum neurotoxins (BoNTs) delivered into the skin and muscle in certain human and animal pain states may exert antinociceptive efficacy though their uptake and transport to central afferent terminals. Cleavage of soluble N-methylaleimide-sensitive attachment protein receptor by BoNTs can impede vesicular mediated neurotransmitter release as well as transport/insertion of channel/receptor subunits into plasma membranes, an effect that can reduce activity-evoked facilitation. Here, we explored the effects of intraplantar botulinum toxin- B (BoNT-B) on peripheral inflammation and spinal nociceptive processing in an inflammatory model of pain. C57BL/6 mice (male) received unilateral intraplantar BoNT (1 U, 30 μL) or saline prior to intraplantar carrageenan (20 μL, 2%) or intrathecal N-methyl-D-aspartate (NMDA), substance P or saline (5 μL). Intraplantar carrageenan resulted in edema and mechanical allodynia in the injected paw and increased phosphorylation of a glutamate subunit (pGluA1ser845) and a serine/threonine-specific protein kinase (pAktser473) in spinal dorsal horn along with an increased incidence of spinal c-Fos positive cells. Pre-treatment with intraplantar BoNT-B reduced carrageenan evoked: (i) allodynia, but not edema; (ii) pGluA1 and pAkt and (iii) c-Fos expression. Further, intrathecal NMDA and substance P each increased dorsal horn levels of pGluA1 and pAkt. Intraplantar BoNT-B inhibited NMDA, but not substance P evoked phosphorylation of GluA1 and Akt. These results suggest that intraplantar toxin is transported centrally to block spinal activation and prevent phosphorylation of a glutamate receptor subunit and a kinase, which otherwise contribute to facilitated states. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. AKAP localizes in a specific subset of TRPV1 and CaV1.2 positive nociceptive rat DRG neurons

    Science.gov (United States)

    Brandao, Katherine E.; Dell’Acqua, Mark L.; Levinson, Simon R.

    2016-01-01

    Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and phosphatases by the scaffolding A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 has been implicated in inflammatory pain by targeting PKA and PKC to the TRPV1 channel in peripheral sensory neurons, thus lowering threshold for activation by multiple inflammatory reagents. However, the expression pattern of AKAP79/150 in peripheral sensory neurons is unknown. In this study we use immunofluorescence microscopy to identify in DRG sections the peripheral neuron subtypes that express the rodent isoform AKAP150, as well as the subcellular distribution of AKAP150 and its potential target ion channels. We found that AKAP150 is predominantly expressed in a subset of small DRG sensory neurons where it is localized at the plasma membrane of the soma, axon initial segment and small fibers. The majority of these neurons is peripherin positive and produces c-fibers, though a small portion produces Aδ-fibers. Furthermore, we demonstrate that AKAP79/150 colocalizes with TRPV1 and CaV1.2 in the soma and axon initial segment. Thus AKAP150 is expressed in small, nociceptive DRG neurons where it is targeted to membrane regions and where it may play a role in the modulation of ion channel phosphorylation states required for hyperalgesia. PMID:21674494

  7. 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

  8. Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses.

    Science.gov (United States)

    Rohrbach, Helene; Korpivaara, Toni; Schatzmann, Urs; Spadavecchia, Claudia

    2009-07-01

    To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. Prospective, blinded, randomized cross-over study. Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was

  9. Building, testing and validating a set of home-made von Frey filaments: a precise, accurate and cost effective alternative for nociception assessment.

    Science.gov (United States)

    de Sousa, Marcelo Victor Pires; Ferraresi, Cleber; de Magalhães, Ana Carolina; Yoshimura, Elisabeth Mateus; Hamblin, Michael R

    2014-07-30

    A von Frey filament (vFF) is a type of aesthesiometer usually made of nylon perpendicularly held in a base. It can be used in paw withdrawal pain threshold assessment, one of the most popular tests for pain evaluation using animal models. For this test, a set of filaments, each able to exert a different force, is applied to the animal paw, from the weakest to the strongest, until the paw is withdrawn. We made 20 low cost vFF using nylon filaments of different lengths and constant diameter glued perpendicularly to the ends of popsicle sticks. They were calibrated using a laboratory balance scale. Building and calibrating took around 4h and confirmed the theoretical prediction that the force exerted is inversely proportional to the length and directly proportional to the width of the filament. The calibration showed that they were precise and accurate. We analyzed the paw withdrawal threshold assessed with the set of home-made vFF and with a high quality commercial set of 5 monofilaments vFF (Stoelting, Wood Dale, USA) in two groups (n=5) of healthy mice. The home-made vFF precisely and accurately measured the hind paw withdrawal threshold (20.3±0.9 g). The commercial vFF have different diameters while our set has the same diameter avoiding the problem of lower sensitivity to larger diameter filaments. Building a set of vFF is easy, cost effective, and depending on the kind of tests, can increase precision and accuracy of animal nociception evaluation. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. High voltage transmission of electrical energy over long distances

    Energy Technology Data Exchange (ETDEWEB)

    Tewari, S W

    1962-07-01

    Technical aspects of ac transmission lines, additional means of improving stability ac transmisson lines, insulation problems, ac transmission by cables, high voltage dc transmission, advantages of dc over ac transmission, disadvantages of dc transmission, use of underground cables for dc transmission, history of the development of conversion equipment; transmission schemes adopted on Gotland Island, Sweden; and economics of ac and dc transmission are discussed.

  11. 76 FR 49841 - Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities

    Science.gov (United States)

    2011-08-11

    ... Commission-approved RTOs and ISOs. The Commission stated that it expected all non-public utility transmission... transmission planning processes that public utility transmission providers in regions outside of RTOs and ISOs...

  12. Harmonics in transmission power systems

    DEFF Research Database (Denmark)

    Wiechowski, Wojciech Tomasz

    . The comparison shows that results obtained used both types of the cores are the same, so it is concluded that both cores can be used for harmonic measurements. Low-inductance resistors are introduced in the secondary circuits, in series with the metering and protective relaying. On those resistors, the harmonic......Some time ago, Energinet.dk, the Transmission System Operator of the 150 kV and 400 kV transmission network in Denmark, had experienced operational malfunctions of some of the measuring and protection equipment. Also an overloading of a harmonic filter has been reported, and therefore, a need...... end only so the ground is not used as a return path. A way to reduce the capacitive coupling is to provide shielding. Harmonic currents are measured using the conventional inductive voltage transformers. Both protective and metering cores were compared if they could be used for harmonic measurements...

  13. Alternative approaches to transmission investment

    Energy Technology Data Exchange (ETDEWEB)

    Vlahos, P. [Ontario Energy Board, Toronto, ON (Canada)

    2004-07-01

    The current regulatory framework at the Ontario Energy Board (OEB) was outlined with reference to the 10-year outlook of the Independent Electricity Market Operator (IMO). Power transmitters currently respond to the IMO's outlook, while the OEB approves applications and cost recovery in rates. The Working Group on Congestion has recommended that the IMO produce a 10-year resource plan, that transmitters produce a 10-year expansion plan, and that the OEB develop a framework for project assessment and rate relief. The Task Force has concluded that merchant transmission is not proven, that transmission is an essential public infrastructure, and that regulatory responsibilities and approval processes should be clarified and streamlined. It was noted that the OEB's approach to regulation should be consistent, clear, predictable, fair, timely and in the public interest.

  14. Transmission X-ray mirror

    International Nuclear Information System (INIS)

    Lairson, B.M.; Bilderback, D.H.

    1982-01-01

    Transmission X-ray mirrors have been made from 400 A to 10 000 A thick soap films and have been shown to have novel properties. Using grazing angles of incidence, low energy X-rays were reflected from the front surface while more energetic X-rays were transmitted through the mirror largely unattenuated. A wide bandpass monochromator was made from a silicon carbide mirror followed by a soap film transmission mirror and operated in the white beam at the cornell High Energy Synchrotron Source (CHESS). Bandpasses of ΔE/E=12% to 18% were achieved at 13 keV with peak efficiencies estimated to be between 55% and 75%, respectively. Several wide angle scattering photographs of stretched polyethylene and a phospholipid were obtained in 10 s using an 18% bandpass. (orig.)

  15. Downlink Transmission of Short Packets

    DEFF Research Database (Denmark)

    Trillingsgaard, Kasper Fløe; Popovski, Petar

    2017-01-01

    Cellular wireless systems rely on frame-based transmissions. The frame design is conventionally based on heuristics, consisting of a frame header and a data part. The frame header contains control information that provides pointers to the messages within the data part. In this paper, we revisit...... the principles of frame design and show the impact of the new design in scenarios that feature short data packets, which are central to various 5G and Internet of Things applications. We~treat framing for downlink transmission in an AWGN broadcast channel with $K$ users, where the sizes of the messages....... This requires changes in the way control information is sent, and it requires that the users need to spend power decoding other messages, thereby increasing the average power consumption. We~show that the common heuristic design is only one point on a curve that represents the tradeoff between latency and power...

  16. Probabilistic costing of transmission services

    International Nuclear Information System (INIS)

    Wijayatunga, P.D.C.

    1992-01-01

    Costing of transmission services of electrical utilities is required for transactions involving the transport of energy over a power network. The calculation of these costs based on Short Run Marginal Costing (SRMC) is preferred over other methods proposed in the literature due to its economic efficiency. In the research work discussed here, the concept of probabilistic costing of use-of-system based on SRMC which emerges as a consequence of the uncertainties in a power system is introduced using two different approaches. The first approach, based on the Monte Carlo method, generates a large number of possible system states by simulating random variables in the system using pseudo random number generators. A second approach to probabilistic use-of-system costing is proposed based on numerical convolution and multi-area representation of the transmission network. (UK)

  17. Exploiting a Transmission Grating Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Ronald E. Bell

    2004-12-08

    The availability of compact transmission grating spectrometers now allows an attractive and economical alternative to the more familiar Czerny-Turner configuration for many high-temperature plasma applications. Higher throughput is obtained with short focal length refractive optics and stigmatic imaging. Many more spectra can be obtained with a single spectrometer since smaller, more densely packed optical input fibers can be used. Multiple input slits, along with a bandpass filter, can be used to maximize the number of spectra per detector, providing further economy. Curved slits can correct for the strong image curvature of the short focal length optics. Presented here are the governing grating equations for both standard and high-dispersion transmission gratings, defining dispersion, image curvature, and desired slit curvature, that can be used in the design of improved plasma diagnostics.

  18. Transmission usage cost allocation schemes

    International Nuclear Information System (INIS)

    Abou El Ela, A.A.; El-Sehiemy, R.A.

    2009-01-01

    This paper presents different suggested transmission usage cost allocation (TCA) schemes to the system individuals. Different independent system operator (ISO) visions are presented using the proportional rata and flow-based TCA methods. There are two proposed flow-based TCA schemes (FTCA). The first FTCA scheme generalizes the equivalent bilateral exchanges (EBE) concepts for lossy networks through two-stage procedure. The second FTCA scheme is based on the modified sensitivity factors (MSF). These factors are developed from the actual measurements of power flows in transmission lines and the power injections at different buses. The proposed schemes exhibit desirable apportioning properties and are easy to implement and understand. Case studies for different loading conditions are carried out to show the capability of the proposed schemes for solving the TCA problem. (author)

  19. Exploiting a Transmission Grating Spectrometer

    International Nuclear Information System (INIS)

    Bell, Ronald E.

    2004-01-01

    The availability of compact transmission grating spectrometers now allows an attractive and economical alternative to the more familiar Czerny-Turner configuration for many high-temperature plasma applications. Higher throughput is obtained with short focal length refractive optics and stigmatic imaging. Many more spectra can be obtained with a single spectrometer since smaller, more densely packed optical input fibers can be used. Multiple input slits, along with a bandpass filter, can be used to maximize the number of spectra per detector, providing further economy. Curved slits can correct for the strong image curvature of the short focal length optics. Presented here are the governing grating equations for both standard and high-dispersion transmission gratings, defining dispersion, image curvature, and desired slit curvature, that can be used in the design of improved plasma diagnostics

  20. Transmission of Influenza A Viruses

    Science.gov (United States)

    Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-01-01

    Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

  1. Unpacking the great transmission debate

    Science.gov (United States)

    Denning, Kathryn

    2010-12-01

    The debate about the wisdom of sending interstellar transmissions is well-known to those involved in SETI, and frustrating for many. Its tendency towards intractability is a result of multiple factors, including: different models of the scientist's role as citizen and/or leader; disparate ideas about society's readiness to cope with frontier science; variable political substrates, particularly ideas concerning individual freedom and state control; competing ideologies of globalization; and the perceived relative risks and benefits of contact. (Variations in the latter, i.e. assessments of the risks and benefits of contact, derive partly from different thinking styles, including tolerance for risk, and partly from inferences based upon episodes of biological and cultural contact on Earth.) Unpacking the debate into its components may be of use to those debating policy about SETI transmissions, or at the very least, help keep in focus what, precisely, the perennial arguments are really about.

  2. Midwest Transmission Workshop II Summary

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Bryan

    2002-12-05

    OAK-B135 After introductions of all participants, Abby Arnold, RESOLVE, reviewed the purpose of the meeting and the agenda. The purpose of the workshop was to share the results of the Midwest Independent System Operator (MISO) scenario development for wind and other fuel sources and the corresponding implications for transmission throughout the MISO control area. The workshop agenda is included in Attachment A.

  3. Transmission and distribution electrical engineering

    CERN Document Server

    Bayliss, Colin

    2003-01-01

    This comprehensive treatment of the theory and practice encountered in the installation and design of transmission and distribution systems for electrical power has been updated and revised to provide the project engineer with all the latest, relevant information to design and specify the correct system for a particular application.Thoroughly updated and revised to include latest developmentsLearn from and Author with extensive experience in managing international projectsFind out the reasoning and implicatons behind the different specifications and methods

  4. Integrated Transmission and Distribution Control

    Energy Technology Data Exchange (ETDEWEB)

    Kalsi, Karanjit [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fuller, Jason C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tuffner, Francis K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lian, Jianming [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhang, Wei [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Laurentiu D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fisher, Andrew R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chassin, Forrest S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hauer, Matthew L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-01-01

    Distributed, generation, demand response, distributed storage, smart appliances, electric vehicles and renewable energy resources are expected to play a key part in the transformation of the American power system. Control, coordination and compensation of these smart grid assets are inherently interlinked. Advanced control strategies to warrant large-scale penetration of distributed smart grid assets do not currently exist. While many of the smart grid technologies proposed involve assets being deployed at the distribution level, most of the significant benefits accrue at the transmission level. The development of advanced smart grid simulation tools, such as GridLAB-D, has led to a dramatic improvement in the models of smart grid assets available for design and evaluation of smart grid technology. However, one of the main challenges to quantifying the benefits of smart grid assets at the transmission level is the lack of tools and framework for integrating transmission and distribution technologies into a single simulation environment. Furthermore, given the size and complexity of the distribution system, it is crucial to be able to represent the behavior of distributed smart grid assets using reduced-order controllable models and to analyze their impacts on the bulk power system in terms of stability and reliability.

  5. METHODS OF POLYMODAL INFORMATION TRANSMISSION

    Directory of Open Access Journals (Sweden)

    O. O. Basov

    2015-03-01

    Full Text Available The research results upon the application of the existing information transmission methods in polymodal info communication systems are presented herein. The analysis of the existing commutation ways and multiplexing schemes has revealed that modern means of telecommunication are capable of providing polymodal information delivery with the required quality to the customer correspondent terminal. Under these conditions substantial capacity resource consumption in the data transmission networks with a simultaneous static time multiplexing is required, however, it is easier to achieve the modality synchronization within that kind of an infrastructure. The data networks with a static time multiplexing demand employing more sophisticated supporting algorithms of the guaranteed data blocks delivery quality. However, due to the stochastic data blocks delays modality synchronizing during the off-line processing is more difficult to provide. Nowadays there are objective preconditions for a data networking realization which is invariable to the applied transmission technology. This capability is defined by a wide (person-to-person application of the optical technologies in the transport infrastructure of the polymodal info communication systems. In case of the availability of the customer terminal and networking functioning matching mode it becomes possible to organize channels in the latter which can adaptively select the most effective networking technology according to the current volume allocation and modality types in the messages.

  6. Wave transmission in nonlinear lattices

    International Nuclear Information System (INIS)

    Hennig, D.; Tsironis, G.P.

    1999-01-01

    The interplay of nonlinearity with lattice discreteness leads to phenomena and propagation properties quite distinct from those appearing in continuous nonlinear systems. For a large variety of condensed matter and optics applications the continuous wave approximation is not appropriate. In the present review we discuss wave transmission properties in one dimensional nonlinear lattices. Our paradigmatic equations are discrete nonlinear Schroedinger equations and their study is done through a dynamical systems approach. We focus on stationary wave properties and utilize well known results from the theory of dynamical systems to investigate various aspects of wave transmission and wave localization. We analyze in detail the more general dynamical system corresponding to the equation that interpolates between the non-integrable discrete nonlinear Schroedinger equation and the integrable Albowitz-Ladik equation. We utilize this analysis in a nonlinear Kronig-Penney model and investigate transmission and band modification properties. We discuss the modifications that are effected through an electric field and the nonlinear Wannier-Stark localization effects that are induced. Several applications are described, such as polarons in one dimensional lattices, semiconductor superlattices and one dimensional nonlinear photonic band gap systems. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  7. Coiled transmission line pulse generators

    Science.gov (United States)

    McDonald, Kenneth Fox

    2010-11-09

    Methods and apparatus are provided for fabricating and constructing solid dielectric "Coiled Transmission Line" pulse generators in radial or axial coiled geometries. The pour and cure fabrication process enables a wide variety of geometries and form factors. The volume between the conductors is filled with liquid blends of monomers, polymers, oligomers, and/or cross-linkers and dielectric powders; and then cured to form high field strength and high dielectric constant solid dielectric transmission lines that intrinsically produce ideal rectangular high voltage pulses when charged and switched into matched impedance loads. Voltage levels may be increased by Marx and/or Blumlein principles incorporating spark gap or, preferentially, solid state switches (such as optically triggered thyristors) which produce reliable, high repetition rate operation. Moreover, these Marxed pulse generators can be DC charged and do not require additional pulse forming circuitry, pulse forming lines, transformers, or an a high voltage spark gap output switch. The apparatus accommodates a wide range of voltages, impedances, pulse durations, pulse repetition rates, and duty cycles. The resulting mobile or flight platform friendly cylindrical geometric configuration is much more compact, light-weight, and robust than conventional linear geometries, or pulse generators constructed from conventional components. Installing additional circuitry may accommodate optional pulse shape improvements. The Coiled Transmission Lines can also be connected in parallel to decrease the impedance, or in series to increase the pulse length.

  8. Automatic Transmission Of Liquid Nitrogen

    Directory of Open Access Journals (Sweden)

    Sumedh Mhatre

    2015-08-01

    Full Text Available Liquid Nitrogen is one of the major substance used as a chiller in industry such as Ice cream factory Milk Diary Storage of blood sample Blood Bank etc. It helps to maintain the required product at a lower temperature for preservation purpose. We cannot fully utilise the LN2 so practically if we are using 3.75 litre LN2 for a single day then around 12 of LN2 450 ml is wasted due to vaporisation. A pressure relief valve is provided to create a pressure difference. If there is no pressure difference between the cylinder carrying LN2 and its surrounding it will results in damage of container as well as wastage of LN2.Transmission of LN2 from TA55 to BA3 is carried manually .So care must be taken for the transmission of LN2 in order to avoid its wastage. With the help of this project concept the transmission of LN2 will be carried automatically so as to reduce the wastage of LN2 in case of manual operation.

  9. Fungal transmission of plant viruses.

    Science.gov (United States)

    Campbell, R N

    1996-01-01

    Thirty soilborne viruses or virus-like agents are transmitted by five species of fungal vectors. Ten polyhedral viruses, of which nine are in the family Tombusviridae, are acquired in the in vitro manner and do not occur within the resting spores of their vectors, Olpidium brassicae and O. bornovanus. Fungal vectors for other viruses in the family should be sought even though tombusviruses are reputed to be soil transmitted without a vector. Eighteen rod-shaped viruses belonging to the furo- and bymovirus groups and to an unclassified group are acquired in the in vivo manner and survive within the resting spores of their vector, O. brassicae, Polymyxa graminis, P. betae, and Spongospora subterranea. The viral coat protein has an essential role in in vitro transmission. With in vivo transmission a site in the coat protein-read through protein (CP-RT) of beet necrotic yellow vein furovirus determines vector transmissibility as does a site in a similar 98-kDa polyprotein of barley mild mosaic bymovirus. The mechanisms by which virions move (or are moved) into and out of the protoplasm of zoospores or of thalli needs study.

  10. 47 CFR 25.212 - Narrowband analog transmissions, digital transmissions, and video transmissions in the GSO Fixed...

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Narrowband analog transmissions, digital transmissions, and video transmissions in the GSO Fixed-Satellite Service. 25.212 Section 25.212 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS...

  11. Transmission and archiving of digitalised radiography

    International Nuclear Information System (INIS)

    Zscherpel, U.; Rose, P.; Kaestner, R.; Mayer, R.; Heinrich, W.; Petesch, M.

    1995-01-01

    The 'TRENDT' research project is concerned with the transmission and archiving of digitalised radiography and with the application of wide band transmission networks in nondestructive material testing. (orig./HP) [de

  12. European bat Lyssavirus transmission among cats, Europe.

    Science.gov (United States)

    Dacheux, Laurent; Larrous, Florence; Mailles, Alexandra; Boisseleau, Didier; Delmas, Olivier; Biron, Charlotte; Bouchier, Christiane; Capek, Isabelle; Muller, Michel; Ilari, Frédéric; Lefranc, Tanguy; Raffi, François; Goudal, Maryvonne; Bourhy, Hervé

    2009-02-01

    We identified 2 cases of European bat lyssavirus subtype 1 transmission to domestic carnivores (cats) in France. Bat-to-cat transmission is suspected. Low amounts of virus antigen in cat brain made diagnosis difficult.

  13. Theory of transmission through disordered superlattices

    DEFF Research Database (Denmark)

    Wacker, Andreas; Hu, Ben Yu-Kuang

    1999-01-01

    We derive a theory for transmission through disordered finite superlattices in which the interface roughness scattering is treated by disorder averaging. This procedure permits efficient calculation of the transmission through samples with large cross sections. These calculations can be performed...

  14. Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain.

    Science.gov (United States)

    Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara; Przewlocka, Barbara; Mika, Joanna

    2016-11-15

    Botulinum neurotoxin serotype A (BoNT/A) shows antinociceptive properties, and its clinical applications in pain therapy are continuously increasing. BoNT/A specifically cleaves SNAP-25, which results in the formation of a non-functional SNARE complex, thereby potently inhibiting the release of neurotransmitters and neuropeptides, including those involved in nociception. The aim of the present study was to determine the effects of BoNT/A (300pg/paw) on pain-related behavior and the levels of glial markers and interleukins in the spinal cord and dorsal root ganglia (DRG) after chronic constriction injury (CCI) to the sciatic nerve in rats. Glial activity was also examined after repeated intraperitoneal injection of minocycline combined with a single BoNT/A injection. Our results show that a single intraplantar BoNT/A injection did not influence motor function but strongly diminished pain-related behaviors in naïve and CCI-exposed rats. Additionally, microglial inhibition using minocycline enhanced the analgesic effects of BoNT/A. Western blotting results suggested that CCI induces the upregulation of the pronociceptive proteins IL-18, IL-6 and IL-1β in the ipsilateral lumbar spinal cord and DRG, but no changes in the levels of the antinociceptive proteins IL-18BP, IL-1RA and IL-10 were observed. Interestingly, BoNT/A injection suppressed the CCI-induced upregulation of IL-18 and IL-1β in the spinal cord and/or DRG and increased the levels of IL-10 and IL-1RA in the DRG. In summary, our results suggest that BoNT/A significantly attenuates pain-related behavior and microglial activation and restores the neuroimmune balance in a CCI model by decreasing the levels of pronociceptive factors (IL-1β and IL-18) and increasing the levels of antinociceptive factors (IL-10 and IL-1RA) in the spinal cord and DRG. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Trends in coordination and transmission service

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    Investor-owned utilities increasingly are taking significant advantage of the benefits available from coordination transactions and transmission service. This chapter describes Edison Electric Institute (EEI's) estimate as to the growth in sales-for-resale (including coordination service) over the past two decades. With respect to transmission service, this chapter describes the significant growth in both the level of transmission service and the number of transmission agreements

  16. Orbiting transmission source for positron tomography

    International Nuclear Information System (INIS)

    Huesman, R.H.; Derenzo, S.E.; Cahoon, J.L.; Geyer, A.B.; Moses, W.W.; Uber, D.C.; Vuletich, T.; Budinger, T.F.

    1988-01-01

    Accidental suppression and effective data rates have been measured for the orbiting transmission source as implemented in the Donner 600-Crystal Positron Tomograph. A mechanical description of the orbiting source and a description of the electronics used to discard scattered and accidental events is included. Since accidental coincidences were the rate-limiting factor in transmission data acquisition, the new method allows us to acquire sufficient transmission data in a shorter time with a more active transmission source

  17. HVDC transmission from nuclear power plant

    International Nuclear Information System (INIS)

    Yoshida, Yukio; Takenaka, Kiyoshi; Taniguchi, Haruto; Ueda, Kiyotaka

    1980-01-01

    HVDC transmission directly from a nuclear power plant is expected as one of the bulk power transmission systems from distant power generating area. Successively from the analysis of HVDC transmission from BWR-type nuclear power plant, this report discusses dynamic response characteristics of HVDC transmission (double poles, two circuits) from PWR type nuclear power plant due to dc-line faults (DC-1LG, 2LG) and ac-line faults (3LG) near inverter station. (author)

  18. Differentiation of Nerve Fibers Storing CGRP and CGRP Receptors in the Peripheral Trigeminovascular System

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Warfvinge, Karin; Blixt, Frank W

    2013-01-01

    Primary headaches such as migraine are postulated to involve the activation of sensory trigeminal pain neurons that innervate intracranial blood vessels and the dura mater. It is suggested that local activation of these sensory nerves may involve dural mast cells as one factor in local inflammation...... and in human dural vessels. The relative distributions of CGRP, CLR, and RAMP1 were evaluated with respect to each other and in relationship to mast cells, myelin, substance P, neuronal nitric oxide synthase, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide. CGRP expression...... was found in thin unmyelinated fibers, whereas CLR and RAMP1 were expressed in thicker myelinated fibers coexpressed with an A-fiber marker. CLR and RAMP1 immunoreactivity colocalized with mast cell tryptase in rodent; however, expression of both receptor components was not observed in human mast cells...

  19. Topics on Electricity Transmission Pricing

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerndal, Mette

    2000-02-01

    Within the last decade we have experienced deregulation of several industries, such as airlines, telecommunications and the electric utility industry, the last-mentioned being the focus of this work. Both the telecommunications and the electricity sector depend on network facilities, some of which are still considered as natural monopolies. In these industries, open network access is regarded as crucial in order to achieve the gains from increased competition, and transmission tariffs are important in implementing this. Based on the Energy Act that was introduced in 1991, Norway was among the first countries to restructure its electricity sector. On the supply side there are a large number of competing firms, almost exclusively hydro plants, with a combined capacity of about 23000 MW, producing 105-125 TWh per year, depending on the availability of water. Hydro plants are characterized by low variable costs of operation, however since water may be stored in dams, water has an opportunity cost, generally known as the water value, which is the shadow price of water when solving the generator's inter temporal profit maximization problem. Water values are the main factor of the producers' short run marginal cost. Total consumption amounts to 112-117 TWh a year, and consumers, even households, may choose their electricity supplier independent of the local distributor to which the customer is connected. In fact, approximately 10% of the households have actually changed supplier. The web-site www.konkurransetilsynet.no indicates available contracts, and www.dinside.no provides an ''energy-calculator'' where one can check whether it is profitable to switch supplier. If a customer buys energy from a remote supplier, the local distributor only provides transportation facilities for the energy and is compensated accordingly. Transmission and distribution have remained monopolized and regulated by the Norwegian Water Resources and Energy

  20. Topics in Electricity Transmission Pricing

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerndal, Mette

    2000-02-01

    Within the last decade we have experienced deregulation of several industries, such as airlines, telecommunications and the electric utility industry, the last-mentioned being the focus of this work. Both the telecommunications and the electricity sector depend on network facilities, some of which are still considered as natural monopolies. In these industries, open network access is regarded as crucial in order to achieve the gains from increased competition, and transmission tariffs are important in implementing this. Based on the Energy Act that was introduced in 1991, Norway was among the first countries to restructure its electricity sector. On the supply side there are a large number of competing firms, almost exclusively hydro plants, with a combined capacity of about 23000 MW, producing 105-125 TWh per year, depending on the availability of water. Hydro plants are characterized by low variable costs of operation, however since water may be stored in dams, water has an opportunity cost, generally known as the water value, which is the shadow price of water when solving the generator's inter temporal profit maximization problem. Water values are the main factor of the producers' short run marginal cost. Total consumption amounts to 112-117 TWh a year, and consumers, even households, may choose their electricity supplier independent of the local distributor to which the customer is connected. In fact, approximately 10% of the households have actually changed supplier. The web-site www.konkurransetilsynet.no indicates available contracts, and www.dinside.no provides an ''energy-calculator'' where one can check whether it is profitable to switch supplier. If a customer buys energy from a remote supplier, the local distributor only provides transportation facilities for the energy and is compensated accordingly. Transmission and distribution have remained monopolized and regulated by the Norwegian Water Resources and Energy

  1. Topics on Electricity Transmission Pricing

    International Nuclear Information System (INIS)

    Bjoerndal, Mette

    2000-02-01

    Within the last decade we have experienced deregulation of several industries, such as airlines, telecommunications and the electric utility industry, the last-mentioned being the focus of this work. Both the telecommunications and the electricity sector depend on network facilities, some of which are still considered as natural monopolies. In these industries, open network access is regarded as crucial in order to achieve the gains from increased competition, and transmission tariffs are important in implementing this. Based on the Energy Act that was introduced in 1991, Norway was among the first countries to restructure its electricity sector. On the supply side there are a large number of competing firms, almost exclusively hydro plants, with a combined capacity of about 23000 MW, producing 105-125 TWh per year, depending on the availability of water. Hydro plants are characterized by low variable costs of operation, however since water may be stored in dams, water has an opportunity cost, generally known as the water value, which is the shadow price of water when solving the generator's inter temporal profit maximization problem. Water values are the main factor of the producers' short run marginal cost. Total consumption amounts to 112-117 TWh a year, and consumers, even households, may choose their electricity supplier independent of the local distributor to which the customer is connected. In fact, approximately 10% of the households have actually changed supplier. The web-site www.konkurransetilsynet.no indicates available contracts, and www.dinside.no provides an ''energy-calculator'' where one can check whether it is profitable to switch supplier. If a customer buys energy from a remote supplier, the local distributor only provides transportation facilities for the energy and is compensated accordingly. Transmission and distribution have remained monopolized and regulated by the Norwegian Water Resources and Energy Directorate (NVE). To prevent cross

  2. HVDC transmission from isorated nuclear power plant

    International Nuclear Information System (INIS)

    Takenaka, Kiyoshi; Takasaki, Masahiro; Ichikawa, Tatemi; Hayashi, Toshiyuki

    1985-01-01

    HVDC transmission directly from nuclear power plant is considered as one of the patterns of long distance and large capacity transmission system. This reports considers two route HVDC transmission from PWR type nuclear power plant, and analyzes dynamic response characteristics due to bus fault, main protection failure and etc. using the AC-DC Power System Simulator. (author)

  3. Voluntary transmission access: The PSI proposal

    International Nuclear Information System (INIS)

    Norris, J.E.

    1990-01-01

    This article examines a proposal from PSI Energy, Inc. (formerly Public Service Company of Indiana) to allow open access to its power transmission facilities and the response of the Federal Energy Regulatory Commission's response to that proposal. The topics discussed include transmission tariffs, competition, market share, expansion of transmission capacity and its funding, and reciprocal agreements to provide similar service

  4. [Heterosexual transmission of HIV infection

    Science.gov (United States)

    Coulaud, J P

    1993-02-01

    The AIDS epidemic has spread rapidly in Africa among the urban impoverished where multiple sexual partners and sexually transmitted diseases are common. Over 80% of the 9 million Africans who will develop AIDS before the year 2000 will have been contaminated sexually. Poverty, multiple sexual partners in the framework of prostitution, and drug addiction are responsible for rapid spread of HIV infection in Southeast Asia, the West India, and Brazil. Drug addiction has played a major role in diffusion of HIV into the general population of Europe and the US. Prevalence rates are much higher in sexually transmitted disease centers in France and the US than among blood donors or pregnant women. Sexually transmitted diseases and heterosexual transmission have been studied in Africas since diagnostic tests became available. Several studies, the majority conducted among prostitutes in Nairobi or Kinshasa and their clients, allow establishment of a list of sexually transmitted diseases associated with increased risk of seroconversion. Genital ulcers within the past 6 months presented a relative risk of 2-4 depending on the series. Urethral or cervical gonorrhea has a lower relative risk of 1.2 in most studies. Absence of circumcision was also a risk factor. Studies were subsequently conducted in Europe on factors favoring sexual transmission. 513 heterosexual couples together for a minimum duration of 18 months and an average of 38 months were included in the Multicenter European Study conducted in 10 centers in 9 countries. The "index" subject was male in 400 cases and female in 113. At entry into the study, 73 of 400 males (18.2%) and 10 of 113 females (8.8%) had already infected their partners. Duration of union, frequency of intercourse, mode of transmission of the index subject, and oral contraceptive use had no effect on risk of transmission. Factors increasing risk of infection included the severity of immunosuppression of the index subject, whether judged by

  5. [The control of vectorial transmission].

    Science.gov (United States)

    Silveira, Antônio Carlos; Dias, João Carlos Pinto

    2011-01-01

    Between 1950 and 1951, the first Prophylactic campaign against Chagas Diseases was carried on in Brazil by the so existing Serviço Nacional de Malária. The actions involving chemical vector control comprehended 74 municipalities along the Rio Grande Valley, between the States of São Paulo and Minas Gerais. Ever since, until 1975, the activities were performed according the availability of resources, being executed with more or less regularity and coverage. At that time, Chagas disease did no represent priority, in comparison with other endemic diseases prevalent in the Country. Even so, taking into account the accumulated data along those 25 years, the volume of work realized cannot be considered despicable. Nevertheless, it was few consistent, in terms of its impact on disease transmission. In 1975, with an additional injection of resources surpassed from the malaria program, plus the methodological systematization of the activities, and with the results of two extensive national inquiries (entomologic and serologic), the activities for vector control could be performed regularly, following two basic principles: interventions in always contiguous areas, progressively enlarged, and sustainability (continuity) of the activities, until being attained determined requirements and purpose previously established. Such actions and strategies lead into the exhaustion of the populations of the principal vector species, Triatoma infestans, no autochthonous and exclusively domiciliary, as well as the control of the domiciliary colonization of autochthonous species important to disease transmission. Vector transmission today is being considered residual, by means of some few native and peridomestic species, such as Triatoma brasiliensis and Triatoma pseudomaculata. There is, also, the risk of progressive domiciliation of some species before considered sylvatic, such as Panstrongylus lutzi and Triatoma rubrovaria. Finally, there is the possibility of the occurrence of cases

  6. Transmission system planning in Ontario

    Energy Technology Data Exchange (ETDEWEB)

    Barrie, D; Macedo, F X; Mcconnach, J S [Ontario Hydro, Toronto, ON (Canada)

    1994-12-31

    In recent years, new and modified approaches to planning the large transmission system that serves the province of Ontario, Canada, have been necessary to accommodate the rapidly changing planning environment including slower uncertain growth, ageing of facilities, integration of demand side management and non utility generation options, increased competitiveness, increased financial stresses and affordable constraints. This paper describes some of the new and modified approaches and tools that have been adopted or are being developed by Ontario Hydro to cope with this changing environment. (author) 9 refs., 4 figs.

  7. Transmission analysis in WDM networks

    DEFF Research Database (Denmark)

    Rasmussen, Christian Jørgen

    1999-01-01

    This thesis describes the development of a computer-based simulator for transmission analysis in optical wavelength division multiplexing networks. A great part of the work concerns fundamental optical network simulator issues. Among these issues are identification of the versatility and user...... the different component models are invoked during the simulation of a system. A simple set of rules which makes it possible to simulate any network architectures is laid down. The modelling of the nonlinear fibre and the optical receiver is also treated. The work on the fibre concerns the numerical solution...

  8. Neutron transmission through crystalline Fe

    International Nuclear Information System (INIS)

    Adib, M.; Habib, N.; Kilany, M.; El-Mesiry, M.S.

    2004-01-01

    The neutron transmission through crystalline Fe has been calculated for neutron energies in the range 10 4 < E<10 eV using an additive formula. The formula permits calculation of the nuclear capture, thermal diffuse and Bragg scattering cross-section as a function of temperature and crystalline form. The obtained agreement between the calculated values and available experimental ones justifies the applicability of the used formula. A feasibility study on using poly-crystalline Fe as a cold neutron filter and a large Fe single crystal as a thermal one is given

  9. Force transmission in epithelial tissues.

    Science.gov (United States)

    Vasquez, Claudia G; Martin, Adam C

    2016-03-01

    In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues. © 2016 Wiley Periodicals, Inc.

  10. nociceptive activities of Elephantorrhiza elephantina

    African Journals Online (AJOL)

    PRECIOUS

    2009-06-15

    Jun 15, 2009 ... The acute toxicity test showed that the plant is relatively safe to use. Key words: Inflammation ... MATERIALS AND METHODS. Plant material ..... plants: An inventory, Natal, South Africa: University of Natal Press. pp. 266-267.

  11. Imaging dopamine transmission in schizophrenia

    International Nuclear Information System (INIS)

    Laruelle, M.

    1998-01-01

    Over the last ten years, several positron emission tomography (PET) and single photon computerized tomography (SPECT) studies of the dopamine (DA) system in patients with schizophrenia were performed to test the hypothesis that DA hyperactivity is associated with this illness. In this paper are reviewed the results of fifteen brain imaging studies comparing indices of DA function in drug naive or drug free patients with schizophrenia and healthy controls: thirteen studies included measurements of Da D 2 receptor density, two studies compared amphetamine-induced DA release, and two studies measured DOPA decarboxylase activity, an enzyme involved in DA synthesis. It was conducted a meta-analysis of the studies measuring D 2 receptor density parameters, under the assumption that all tracers labeled the same population of D 2 receptors. This analysis revealed that, compared to healthy controls, patients with schizophrenia present a significant but mild elevation of D 2 receptor density parameters and a significant larger variability of these indices. It was found no statistical evidence that studies performed with radiolabeled butyrophenones detected a larger increase in D 2 receptor density parameters than studies performed with other radioligands, such as benzamides. Studies of presynaptic activity revealed an increase in DA transmission response to amphetamine challenge, and an increase in DOPA decarboxylase activity. Together, these data are compatible with both pre- and post-synaptic alterations of DA transmission in schizophrenia. Future studies should aim at a better characterization of these alterations, and at defining their role in the pathophysiology of the illness

  12. Wildlife and electric power transmission

    Science.gov (United States)

    Ellis, D.H.; Goodwin, J.G.; Hunt, J.R.; Fletcher, John L.; Busnel, R.G.

    1978-01-01

    Hundreds of thousands of miles of transmission lines have been introduced into our natural environment. These lines and their corridors can be damaging or beneficial to wildlife communities depending on how they are designed, where they are placed, and when they are constructed and maintained. With the current trend toward UHV systems, new problems (associated with additional increments in audible noise, electric and magnetic force fields, etc.) must be addressed. We recommend the following areas for careful study: (1) the response of wilderness species to transmission lines and line construction and maintenance activities (2) the magnitude of bird collision and electrocution mortality, (3) the response of power corridor and power tower in habiting wildlife to laboratory and field doses of electro-chemical oxidants, corona noise, electric and magnetic fields, etc., (4) the productivity of tower inhabiting birds compared with nearby non-tower nesters, and (5) the influence of powerline corridors on mammalian and avian migration patterns. It is our hope that the questions identified in this study will help stimulate further research so that we can maximize wildlife benefits and minimize wildlife detriments.

  13. neutron transmission through crystalline materials

    International Nuclear Information System (INIS)

    El Mesiry, M.S.

    2011-01-01

    The aim of the present work is to study the neutron transmission through crystalline materials. Therefore a study of pyrolytic graphite (PG) as a highly efficient selective thermal neutron filter and Iron single crystal as a whole one, as well as the applicability of using their polycrystalline powders as a selective cold neutron filters is given. Moreover, the use of PG and iron single crystal as an efficient neutron monochromator is also investigated. An additive formula is given which allows calculating the contribution of the total neutron cross-section including the Bragg scattering from different )(hkl planes to the neutron transmission through crystalline iron and graphite. The formula takes into account their crystalline form. A computer CFe program was developed in order to provide the required calculations for both poly- and single-crystalline iron. The validity of the CFe program was approved from the comparison of the calculated iron cross-section data with the available experimental ones. The CFe program was also adapted to calculate the reflectivity from iron single crystal when it used as a neutron monochromator The computer package GRAPHITE, developed in Neutron Physics laboratory, Nuclear Research Center, has been used in order to provide the required calculations for crystalline graphite in the neutron energy range from 0.1 meV to 10 eV. A Mono-PG code was added to the computer package GRAPHITE in order to calculate the reflectivity from PG crystal when it used as a neutron monochromator.

  14. [Human transmissible subacute spongiform encephalopathy].

    Science.gov (United States)

    Dormont, D

    1994-05-01

    Human transmissible spongiform encephalopathies (TSE) are rare chronic subacute degenerative diseases of the central nervous system (CNS) which include Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia (FFI). CJD can be either inherited or sporadic. All these diseases are always fatal. Neuropathological features are mainly constituted of neuronal vacuolisation, neuronal death, gliosis with hyperastrocytosis; plaques might be evidenced in kuru and GSS. Neither inflammatory syndrome nor demyelination is detectable. No virus like structure could be identified reproducibly. Human TSE are transmissible to non human primates and rodents. Iatrogenic CJD have been described after tissue grafting (cornea, dura mater), neurosurgery, electrophysiology investigation, and treatment with pituitary derived gonadotrophins and growth hormone. Molecular biochemistry of the CNS investigation revealed that a host encoded protein, the prion protein (PrP), accumulates proportionally to the infectious titer: this abnormality is the only detectable hallmark in TSE. Infectious fractions contain no detectable specific nucleic acid, and are mainly constituted of PrP under an isoform which resists to proteinase K digestion (PrP-res). The PrP gene (PRNP) is located on chromosome 20 in humans. Several mutations of this gene have been described in all inherited TSE (CJD, GSS, and IFF). No treatment is available today. Agents inducing TSE (TSA) are not known: several authors claim that TSA are only constituted of PrP-res; others support the hypothesis of a conventional agent with a specific genetic information.

  15. Money and transmission of bacteria.

    Science.gov (United States)

    Gedik, Habip; Voss, Timothy A; Voss, Andreas

    2013-08-28

    Money is one of the most frequently passed items in the world. The aim of this study was to ascertain the survival status of bacteria including Staphylococcus aureus, Escherichia coli, and Vancomycin- Resistant Enterococci (VRE) on banknotes from different countries and the transmission of bacteria to people who come in contact with the banknotes. The survival rate was highest for the Romanian Leu yielding all three microorganisms used after both three and six hours of drying. Furthermore, the Leu was the only banknote to yield VRE after one day of drying. Other currencies either enabled the survival of Extended-Spectrum Beta-Lactamases (ESBL) and VRE (e.g. Euro), but not of MRSA, or the other way round (e.g. US Dollar). While a variety of factors such as community hygiene levels, people's behaviour, and antimicrobial resistance rates at community level obviously have influence on the transmission of resistant microorganisms, the type of banknote-paper may be an additional variable to consider.

  16. TRANSMISSIBLE VENEREAL TUMOR - LITERATURE REVIEW

    Directory of Open Access Journals (Sweden)

    T. R. B Berndt

    2016-11-01

    Full Text Available Transmissible venereal tumor (TVT is a contagious disease among the family of canines. Has a high prevalence in temperate regions and mainly affects male and female dogs wandering. Transmissible venereal tumor's main characteristic is a sexually transmitted cancer, through intercourse, and also transmitted through cell transplantation, an animal that has the disease to another Sound, which has an abrasion or epithelial discontinuity through licking or contact direct to neoplasia. It has no known etiology, although some authors suggest that there may be some virus as an agent. Is macroscopically observed as a crumbly mass, ulcerated, hemorrhagic, with the appearance of cauliflower. Their cells, if observed microscopically, have very clear, round and giant nucleus stained cytoplasm, and the presence of vacuolated cells in mitosis. The diagnosis can be accomplished by fine needle aspiration cytology, "imprint", histopathology, imaging tests such as x-ray and ultrasound, which are used for observation of metastases in internal organs. The main treatment is chemotherapy with substances such as vincristine dose of 0.5 to 0.7 mg / m², intra venous (IV, or from 0.0125 to 0.025 mg / kg IV once a week, four to eight weeks, and for animals which have acquired resistance to vincristine sulfate, is associated with the chemotherapeutic doxorubicin at a dose of 30 mg / m² IV once a week for four to eight weeks. Some protocols include prednisolone associated with vincristine sulfate for the treatment of Extragenital TVT.

  17. The limits of HVDC transmission

    International Nuclear Information System (INIS)

    Pickard, William F.

    2013-01-01

    Renewable energy is abundant, but not necessarily near the urban centers where it will be used. Therefore, it must be transported; and this transport entails a systemic energy penalty. In this paper simple qualitative calculations are introduced to show (i) that high-voltage direct-current (HVDC) power lines for megameter and greater distances are unlikely to achieve power capacities much beyond 2 GW, although they can be paralleled; (ii) that most sources and sinks of electric power are rather less than 10,000 km apart; (iii) that such long lines can be constructed to have transmission losses -tilde 2%; and (iv) that lines of such low loss in fact meet minimal standards of intergenerational equity. - Highlights: • Renewable Energy is abundant, but not necessarily near population centers. • Its transportation requires energy and can be a major systemic inefficiency. • HVDC can be transmitted 10,000 km with 2% loss and near-optimal embodied energy. • Such transmission meets the requirements of intergenerational equity

  18. Information transmission on hybrid networks

    Science.gov (United States)

    Chen, Rongbin; Cui, Wei; Pu, Cunlai; Li, Jie; Ji, Bo; Gakis, Konstantinos; Pardalos, Panos M.

    2018-01-01

    Many real-world communication networks often have hybrid nature with both fixed nodes and moving modes, such as the mobile phone networks mainly composed of fixed base stations and mobile phones. In this paper, we discuss the information transmission process on the hybrid networks with both fixed and mobile nodes. The fixed nodes (base stations) are connected as a spatial lattice on the plane forming the information-carrying backbone, while the mobile nodes (users), which are the sources and destinations of information packets, connect to their current nearest fixed nodes respectively to deliver and receive information packets. We observe the phase transition of traffic load in the hybrid network when the packet generation rate goes from below and then above a critical value, which measures the network capacity of packets delivery. We obtain the optimal speed of moving nodes leading to the maximum network capacity. We further improve the network capacity by rewiring the fixed nodes and by considering the current load of fixed nodes during packets transmission. Our purpose is to optimize the network capacity of hybrid networks from the perspective of network science, and provide some insights for the construction of future communication infrastructures.

  19. Transmission access issues: Present and future

    International Nuclear Information System (INIS)

    Bahl, P.K.; Gray, R.G.

    1992-01-01

    In recent years, the electric industry has undergone dramatic changes as the federal and state governments have encouraged bulk power production by Independent Power Producers (IPPS) and Qualified Facilities (QFs). With decentralization and the consequent competition in the field of bulk power production, there has emerged the problem of non-utility generators (NUGS) and of transmission dependent utilities accessing the existing transmission systems owned by electric utilities. This paper presents current and future issues related to transmission access by IPPS, QFs and transmission dependent utilities. These issues include: (a) impact on system reliability, (b) impact of pricing strategies, (c) changes in state and federal regulations, (d) transmission proposals by various entities, (e) present access arrangements, (f) formation of the Western Systems Power Pool (WSPP), and (g) siting difficulties. The transmission access problem warrants consideration of transmission services, coordination among electric utilities, joint planning on a regional basis, and accommodation of IPPs and NUGs

  20. APEnet+ 34 Gbps data transmission system and custom transmission logic

    International Nuclear Information System (INIS)

    Ammendola, R; Biagioni, A; Frezza, O; Lonardo, A; Cicero, F Lo; Paolucci, P S; Rossetti, D; Simula, F; Tosoratto, L; Vicini, P

    2013-01-01

    APEnet+ is a point-to-point, low-latency, 3D-torus network controller integrated in a PCIe Gen2 board based on the Altera Stratix IV FPGA. We characterize the transmission system (embedded transceivers driving external QSFP+ modules) analyzing signal integrity, throughput, latency, BER and jitter at different data rates up to 34 Gbps. We estimate the efficiency of a custom logic able to sustain 2.6 GB/s per link with an FPGA on-chip memory footprint of 40 KB, providing deadlock-free routing and systemic awareness of faults. Finally, we show the preliminary results obtained with the embedded transceivers of a next-generation FPGA and outline some ideas to increase the performance with the same FPGA memory footprint

  1. APEnet+ 34 Gbps data transmission system and custom transmission logic

    Energy Technology Data Exchange (ETDEWEB)

    Ammendola, R [INFN Sezione di Roma Tor Vergata, Via della Ricerca Scientifica, 1 - 00133 Roma Italy (Italy); Biagioni, A; Frezza, O; Lonardo, A; Cicero, F Lo; Paolucci, P S; Rossetti, D; Simula, F; Tosoratto, L; Vicini, P [INFN Sezione di Roma, P.le Aldo Moro, 2 - 00185 Roma Italy (Italy)

    2013-12-01

    APEnet+ is a point-to-point, low-latency, 3D-torus network controller integrated in a PCIe Gen2 board based on the Altera Stratix IV FPGA. We characterize the transmission system (embedded transceivers driving external QSFP+ modules) analyzing signal integrity, throughput, latency, BER and jitter at different data rates up to 34 Gbps. We estimate the efficiency of a custom logic able to sustain 2.6 GB/s per link with an FPGA on-chip memory footprint of 40 KB, providing deadlock-free routing and systemic awareness of faults. Finally, we show the preliminary results obtained with the embedded transceivers of a next-generation FPGA and outline some ideas to increase the performance with the same FPGA memory footprint.

  2. Effectiveness of monopolar dielectric transmission of pulsed electromagnetic fields for multiple sclerosis-related pain: A pilot study.

    Science.gov (United States)

    Hochsprung, A; Escudero-Uribe, S; Ibáñez-Vera, A J; Izquierdo-Ayuso, G

    2018-05-08

    Pain is highly prevalent in patients with multiple sclerosis (MS); it is chronic in 50% of cases and is classified as nociceptive, neuropathic, or mixed-type. Pain affects quality of life, sleep, and the activities of daily living. Electrotherapy is an interesting alternative or complementary treatment in the management of pain in MS, with new innovations constantly appearing. This study evaluates the effectiveness of treatment with monopolar dielectric transmission of pulsed electromagnetic fields (PEMF) for pain associated with MS. We performed a randomised, placebo-controlled clinical trial including 24 patients, who were assessed with the Brief Pain Inventory, the Multiple Sclerosis International Quality of Life questionnaire, the Beck Depression Inventory, and the Modified Fatigue Impact Scale. Statistically significant improvements were observed in maximum and mean pain scores, as well as in the impact of pain on work, personal relationships, and sleep and rest. Not significant differences were found between the treatment and placebo groups. Treatment with PEMF may be effective in reducing pain in patients with MS, although further research is necessary to confirm its effectiveness over placebo and to differentiate which type of pain may be more susceptible to this treatment. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Transmission policy in the United States

    International Nuclear Information System (INIS)

    Joskow, P.L.

    2005-01-01

    This paper provides an overview of the development of electric power transmission access, pricing and investment policies in the US over the last 15 years and evaluates the current state of those policies. Pre-liberalization transmission access and pricing policies are reviewed first since more recent policies have evolved from them. FERC's efforts to ensure that transmission owning utilities provide non-discriminatory access and pricing to wholesale transmission customers, culminating in Order 888 and 889 are discussed. These rules did not respond to problems created by a highly balkanized transmission system and only partially responded to problems caused by common ownership and operation of transmission networks with generating and marketing businesses in the same regions. These problems motivated FERC to seek to create Regional Transmission Organizations (RTO) meeting a long list of criteria related to governance, network operations, transmission pricing and investment as reflected in Order 2000. The slow pace of 'voluntary' reform following Order 2000 led FERC to issue a proposed Standard Market Design Rule (SMD) which provided more detailed prescriptions for wholesale market design, network operations, regional planning, resource adequacy, and transmission investment. The SMD rule confronted enormous resistance from groups of utilities and states that had not embraced an electricity sector liberalization agenda. However, many of the provisions of the SMD are being implemented by the RTOs and ISOs in the Northeast and Midwest. PJM's market rules and transmission pricing, planning and investment policies are reviewed as an articulation of FERC's RTO and SMD visions. (author)

  4. Magnetically insulated transmission line oscillator

    Science.gov (United States)

    Bacon, L.D.; Ballard, W.P.; Clark, M.C.; Marder, B.M.

    1987-05-19

    A magnetically insulated transmission line oscillator employs self-generated magnetic fields to generate microwave energy. An anode of the oscillator includes slow-wave structures which are formed of a plurality of thin conductive vanes defining cavities therebetween, and a gap is formed between the anode and a cathode of the oscillator. In response to a pulsed voltage applied to the anode and cathode, self-generated magnetic fields are produced in a cross-field orientation with respect to the orientation of the electric field between the anode and the cathode. The cross-field magnetic fields insulate the flow of electrons in the gap and confine the flow of electrons within the gap. 11 figs.

  5. Multimedia signal coding and transmission

    CERN Document Server

    Ohm, Jens-Rainer

    2015-01-01

    This textbook covers the theoretical background of one- and multidimensional signal processing, statistical analysis and modelling, coding and information theory with regard to the principles and design of image, video and audio compression systems. The theoretical concepts are augmented by practical examples of algorithms for multimedia signal coding technology, and related transmission aspects. On this basis, principles behind multimedia coding standards, including most recent developments like High Efficiency Video Coding, can be well understood. Furthermore, potential advances in future development are pointed out. Numerous figures and examples help to illustrate the concepts covered. The book was developed on the basis of a graduate-level university course, and most chapters are supplemented by exercises. The book is also a self-contained introduction both for researchers and developers of multimedia compression systems in industry.

  6. Electricity transmission pricing and technology

    International Nuclear Information System (INIS)

    Einhorn, M.; Siddiqi, R.

    1996-01-01

    The electric utility industry and its stake holders in the United States appear to be at a critical juncture in time. Powerful forces of global proportions are propelling the industry instinctively and in a secular fashion towards restructuring. That the industry will change is a fait accomplii. The nature and timing of the change is still a matter of intense debate, however. Because of the evolution of the industry into its present-day form, i.e. regulated local monopolies in their designated franchise service territories, the relative roles and expectations of various institutions would have to change to conform to the new state in the future. In either encouraging, or allowing this change to happen, society is essentially saying that future societal welfare would be better served by the changed structure contemplated. What that assumption translates into in more direct terms is that creation of future wealth would be better accomplished through redistribution of wealth today. Thoughtful individuals recognize the enormous responsibility placed upon the various entities empowered with jurisdiction over the timing and nature of the structural change. They are trying hard to bring analytical rigor to bear on the debate. One very critical element of this debate on restructuring is the issue of the treatment of transmission. The issue has been variously labeled transmission access, or pricing. Volumes have been written and spoken on this topic. We felt that there was a pressing need to assemble a volume which would serve as a one-stop source for varied viewpoints and comprehensive coverage of the subject, both technical and economic. 58 figs., 23 tabs., 103 refs

  7. Transmission : key to the Alberta market

    International Nuclear Information System (INIS)

    Lyons, D.

    2003-01-01

    AltaLink is Canada's first independent transmission company with 11,000 kilometres (km) of lines and 250 substations. It possesses a unique ownership structure with strong technical partners and financial capability. No major transmission system has been built in the last fifteen years in Alberta. The author examined the situation of power transmission in Alberta, indicating that developments should include capacity increase out of Fort McMurray, and better market integration with both British Columbia and the Pacific Northwest. An efficient and effective market requires ample transmission capacity, which would allow for trade and competition, access for efficient generators, and access to regional markets. New transmission must be planned and achieved in a proactive manner. Generation developers must be assured that transmission will be available, and that tariffs and loss factors will be predictable and stable. figs

  8. Why transmission is still the critical link

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, V. [ESBI Alberta Ltd., Calgary, AB (Canada)

    2002-07-01

    This paper describes the important role that transmission plays in the competitive electric power industry in North America and around the world. In the past several years the transmission sector has experienced a lack of investment, congestion on transmission networks, merchant transmission development, and the creation of Regional Transmission Organizations (RTOs). The transmission grid is central to the reliability of the entire electricity system. It also plays a vital role in promoting efficient markets in electricity. The author discusses the consequences of inadequate investment to this critical link within the power industry. He also discusses how much investment is needed, and the challenges and solutions to building an infrastructure. The integrated electric system and the electricity industry in Alberta is very different from those in the United Sates, but the issues facing the industry are the same. The challenge is the sharp increase in the number of system access requests by new generators combined with the difficulties in siting new transmission lines. There are 17,000 km of transmission lines in Alberta, at voltages ranging from 69 kV to 500 kV. There are also connections between neighbouring provinces. The transmission lines have a value of C$1.5 billion. Since there have been no major additions to the transmission grid since the mid-1980s, significant investments in the coming years will have a disproportionate impact on the cost of transmission. Two merchant transmission projects have been proposed. The first will enhance transfer of electricity between Alberta and Saskatchewan by 150 MW, and the second is proposed to be a 1,500 MW, 500 kV DC line from the Fort McMurray area to the Pacific Northwest. 5 figs.

  9. Transmission and capacity pricing and constraints

    International Nuclear Information System (INIS)

    Fusco, M.

    1999-01-01

    A series of overhead viewgraphs accompanied this presentation which discussed the following issues regarding the North American electric power industry: (1) capacity pricing transmission constraints, (2) nature of transmission constraints, (3) consequences of transmission constraints, and (4) prices as market evidence. Some solutions suggested for pricing constraints included the development of contingent contracts, back-up power in supply regions, and new line capacity construction. 8 tabs., 20 figs

  10. Transmissible Spongiform Encephalopathy and Meat Safety

    Science.gov (United States)

    Ward, Hester J. T.; Knight, Richard S. G.

    Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.

  11. Macedonian transmission grid capability and development

    International Nuclear Information System (INIS)

    Naumoski, K.; Achkoska, E.; Paunoski, A.

    2015-01-01

    The main task of the transmission grid is to guarantee evacuation of electricity from production facilities and, at the same time, supply the electricity to all customers, in a secure, reliable and qualitative manner. During the last years, transmission grid goes through the period of fast and important development, as a result of implementation of renewable and new technologies and creation of internal European electricity market. Due to these reasons, capacity of the existing grid needs to be upgraded either with optimization of existing infrastructure or constructing the new transmission projects. Among the various solutions for strengthening the grid, the one with the minimal investment expenses for construction is selected. While planning the national transmission grid, MEPSO planners apply multi-scenarios analyses, in order to handle all uncertainties, particularly in the forecasts on loads, production and exchange of electricity, location and size of the new power plants, hydrological conditions, integration of renewable sources and the evolution of the electricity market. Visions for development of European transmission grid are also considered. Special attention in the development plan is paid to modelling of power systems in the region of South-Eastern Europe and covering a wider area of the regional transmission grid with simulations of various market transactions. Macedonian transmission grid is developed to satisfy all requirements for electricity production/supply and transits, irrespective which scenario will be realized on long-term basis. Transmission development plan gives the road map for grid evolution from short-term and mid-term period towards long-term horizons (15-20 years ahead). While creating long-term visions, a big challenge in front of transmission planners is implementation of NPP. The paper gives overview of the planning process of Macedonian transmission grid,comprising: definition of scenarios,planning methodology and assessment of

  12. Response analysis on nonuniform transmission line

    Directory of Open Access Journals (Sweden)

    Cvetković Zlata

    2005-01-01

    Full Text Available Transients on a loss less exponential transmission line with a pure resistance load are presented in this paper. The approach is based on the two-port presentation of the transmission line. Using Picard-Carson's method the transmission line equations are solved. The relationship between source voltage and the load voltage in s-domain is derived. All the results are plotted using program package Mathematica 3.0.

  13. Power transmission pricing: issues and international experience

    International Nuclear Information System (INIS)

    Bodenhoefer, H.J.; Wohlgemuth, N.

    2001-01-01

    A key aspect of electricity industry reorganization is transmission pricing because it heavily influences the degree of effective competition in 'liberalized' electricity markets. this paper presents an overview transmission pricing models, of issues related to an effective design of a transmission pricing approach, and presents approaches implemented internationally. A conclusion is that, due to the great number of institutional designs of electricity market organizations, particularly in Europe, it will be difficult to design/implement a model of cross-border transmission pricing that is capable of inducing a high degree of non-discriminatory international competition in electricity markets. (author)

  14. Transmission Line Security Monitor: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    John Svoboda

    2011-04-01

    The Electric Power Transmission Line Security Monitor System Operational Test is a project funded by the Technical Support Working Group (TSWG). TSWG operates under the Combating Terrorism Technical Support Office that functions under the Department of Defense. The Transmission Line Security Monitor System is based on technology developed by Idaho National Laboratory. The technology provides a means for real-time monitoring of physical threats and/or damage to electrical transmission line towers and conductors as well as providing operational parameters to transmission line operators to optimize transmission line operation. The end use is for monitoring long stretches of transmission lines that deliver electrical power from remote generating stations to cities and industry. These transmission lines are generally located in remote transmission line corridors where security infrastructure may not exist. Security and operational sensors in the sensor platform on the conductors take power from the transmission line and relay security and operational information to operations personnel hundreds of miles away without relying on existing infrastructure. Initiated on May 25, 2007, this project resulted in pre-production units tested in realistic operational environments during 2010. A technology licensee, Lindsey Manufacturing of Azusa California, is assisting in design, testing, and ultimately production. The platform was originally designed for a security monitoring mission, but it has been enhanced to include important operational features desired by electrical utilities.

  15. Fundamental study of bulk power HVDC transmission

    International Nuclear Information System (INIS)

    1981-01-01

    Study on the HVDC power transmission have been conducted since 1956. Shinshinano-Frequency Changer had been operated at first on 1977, as our home product, and Hokkaido-Honshu DC transmission also realized at 1979. Research and Development of the bulk power HVDC have been promoted by the UHV transmission special committee in our Institute from 1980. This paper is a comprehensive report published in the parts of operating control, insulation of DC line and countermeasure of fault current, and interferences in order to contribute for planning, design and operating of the UHV DC transmission in future. (author)

  16. VT Digital Line Graph Miscellaneous Transmission Lines

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This datalayer is comprised of Miscellaineous Transmission Lines. Digital line graph (DLG) data are digital representations of cartographic...

  17. Nuclear stopping in transmission experiments

    International Nuclear Information System (INIS)

    Glazov, Lev G.; Sigmund, Peter

    2003-01-01

    Energy-loss spectra, mean and peak energy loss, and straggling due to elastic nuclear scattering have been studied theoretically as a function of target thickness and deflection angle of an initially monochromatic and well-collimated ion beam. The goal of this work has been to provide a generally valid scheme for nuclear-stopping corrections, allowing to determine electronic-stopping forces from energy-loss spectra measured in transmission geometry. Calculations have been based on the generalized Bothe-Landau theory of energy loss and multiple scattering. Our peak energy losses at zero emergence angle show close (∼10%) agreement with predictions of Fastrup et al. on the basis of the Bohr-Williams theory. However, predicted mean and peak energy losses are found to more sensitively depend on the underlying interatomic potential than unrestricted, i.e. angle-integrated mean or peak energy losses. Both elastic energy loss and multiple scattering are known to obey scaling laws involving only two combinations of the pertinent variables and atomic parameters. The dependence on deflection angle and foil thickness of mean and peak energy loss obeys a simple combination of these scaling laws. Comments are made on potential errors due to uncertainties in the nuclear-stopping correction applied in the literature with specific reference to central papers in low-velocity stopping

  18. Beta attenuation transmission system (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm/sup 2/, of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A /sup 90/Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (..mu..P) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined.

  19. Monochromated scanning transmission electron microscopy

    International Nuclear Information System (INIS)

    Rechberger, W.; Kothleitner, G.; Hofer, F.

    2006-01-01

    Full text: Electron energy-loss spectroscopy (EELS) has developed into an established technique for chemical and structural analysis of thin specimens in the (scanning) transmission electron microscope (S)TEM. The energy resolution in EELS is largely limited by the stability of the high voltage supply, by the resolution of the spectrometer and by the energy spread of the source. To overcome this limitation a Wien filter monochromator was recently introduced with commercially available STEMs, offering the advantage to better resolve EELS fine structures, which contain valuable bonding information. The method of atomic resolution Z-contrast imaging within an STEM, utilizing a high-angle annular dark-field (HAADF) detector can perfectly complement the excellent energy resolution, since EELS spectra can be collected simultaneously. In combination with a monochromator microscope not only high spatial resolution images can be recorded but also high energy resolution EELS spectra are attainable. In this work we investigated the STEM performance of a 200 kV monochromated Tecnai F20 with a high resolution Gatan Imaging Filter (HR-GIF). (author)

  20. Preserving information in neural transmission.

    Science.gov (United States)

    Sincich, Lawrence C; Horton, Jonathan C; Sharpee, Tatyana O

    2009-05-13

    Along most neural pathways, the spike trains transmitted from one neuron to the next are altered. In the process, neurons can either achieve a more efficient stimulus representation, or extract some biologically important stimulus parameter, or succeed at both. We recorded the inputs from single retinal ganglion cells and the outputs from connected lateral geniculate neurons in the macaque to examine how visual signals are relayed from retina to cortex. We found that geniculate neurons re-encoded multiple temporal stimulus features to yield output spikes that carried more information about stimuli than was available in each input spike. The coding transformation of some relay neurons occurred with no decrement in information rate, despite output spike rates that averaged half the input spike rates. This preservation of transmitted information was achieved by the short-term summation of inputs that geniculate neurons require to spike. A reduced model of the retinal and geniculate visual responses, based on two stimulus features and their associated nonlinearities, could account for >85% of the total information available in the spike trains and the preserved information transmission. These results apply to neurons operating on a single time-varying input, suggesting that synaptic temporal integration can alter the temporal receptive field properties to create a more efficient representation of visual signals in the thalamus than the retina.

  1. Transmission of Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Giuseppina Oderda

    1999-01-01

    Full Text Available Helicobacter pylori infection is one of the most common bacterial infections worldwide. It is accepted as the major cause of chronic gastritis, peptic ulcer, carcinoma of the distal part of the stomach and gastric lymphoma. However, how and when the infection is acquired remain largely unknown. Identification of mode of transmission is vital for developing preventive measures to interrupt its spread, but studies focused on this issue are difficult to implement. From epidemiological studies, it is known that there are great differences in the prevalence of infection in different populations and in ethnic groups originating from high prevalence regions. This is likely related to inferior hygienic conditions and sanitation. In developing countries, infection occurs at a much earlier age. In developed countries, the prevalence of infection is related to poor socioeconomic conditions, particularly density of living. Humans seem to be the only reservoir of H pylori, which spread from person to person by oral-oral, fecal-oral or gastro-oral routes. Most infections are acquired in childhood, possibly from parents or other children living as close contacts. Infection from the environment or from animals cannot be entirely excluded.

  2. Beta attenuation transmission system (BATS)

    International Nuclear Information System (INIS)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm 2 , of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A 90 Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (μP) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined

  3. 77 FR 64890 - Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities

    Science.gov (United States)

    2012-10-24

    ... regional transmission organizations (RTOs) are required to follow regarding the availability of long-term.... P 649. \\51\\ Id. P 746. \\52\\ As Transmission Access Policy Study Group also recognizes, not all RTOs...

  4. Quantifying Transmission Investment in Malaria Parasites.

    Directory of Open Access Journals (Sweden)

    Megan A Greischar

    2016-02-01

    Full Text Available Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.

  5. Wireless transmission: state of research, applications, trends

    International Nuclear Information System (INIS)

    Berger, A.

    2016-01-01

    At the end of the 19th century Nikola Tesla started his work in the field of wireless energy transmission. More than 100 years after Tesla, the progress in modern semiconductor technology offer developers the possibility to realize highly efficient systems and have led to a revival of wireless energy transmission. The application ranges from the transmission of a few milliwatts in biomedical applications, over a few watts for the charging of mobile phones, to hundreds of kilowatts in the automotive sector. Depending on the used method, the possible transmission distances vary between a few centimeters up to thousands of kilometers. The physical basis of these technologies is the transmission of energy by electromagnetic waves. State-of-the-art systems use wavelengths ranging from radio waves to microwaves, to ultraviolet light. Current research focuses on optimizing transmission efficiency, increasing the possible transmission distance between transmitter and receiver, and improving spatial freedom of movement. This lecture gives an overview of the different approaches of wireless energy transmission and their physical background, the established industrial standards and the current state of research. In addition, the advantages and disadvantages of the individual methods are illustrated by selected commercial and scientific applications. (rössner) [de

  6. Virus isolation: Specimen type and probable transmission

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Virus isolation: Specimen type and probable transmission. Over 500 CHIK virus isolations were made. 4 from male Ae. Aegypti (?TOT). 6 from CSF (neurological involvement). 1 from a 4-day old child (transplacental transmission.

  7. Transmission tariffs - Principles, structure, aims and demands

    International Nuclear Information System (INIS)

    Groenli, Helle; Sand, Kjell

    1997-11-01

    The report deals with several optimization techniques for increasing the efficiency of electric grid operation in Norway. Methods and tools used for the determination of transmission costs are discussed such as partial transmission tariffs and Ramsey-pricing etc. 7 refs., 13 figs., 6 tabs

  8. Contract networks for competition in transmission grids

    International Nuclear Information System (INIS)

    Hogan, W.W.

    1992-01-01

    Increased reliance on competition in energy markets requires pricing, access, and investment reform for the essential transmission grids. Due to the complexity of the network interactions, the usual analogies to economic concepts from other settings have little or no meaning in transmission grids. A contract network framework builds from first principles to define the conditions of an efficient market. 8 refs

  9. The interior transmission spectrum in one dimension

    International Nuclear Information System (INIS)

    Hickmann, Kyle S

    2012-01-01

    This paper seeks conditions on acoustic profiles c(x) and b(x) which imply the existence of intervals free of transmission eigenvalues. The existence of intervals free of transmission eigenvalues has important implications in the question of unique recovery of the acoustic profile for inverse acoustic scattering theory using the linear sampling method and for the inverse source problem in thermoacoustic tomography. We examine the interior transmission spectrum relative to two acoustic profiles on the unit interval. This research includes the case when the difference of the two acoustic profiles changes sign and is, to the author's knowledge, the only work to date on the interior transmission spectrum allowing this behavior. It is shown that for a large class of acoustic profiles the transmission spectrum is asymptotically sparse. The spectrum exhibits three distinct types of behavior dependent on the relation of the two acoustic profiles. Numerical examples of each type of behavior are given which show how the transmission eigenvalues are distributed depending on the relation between c(x) and b(x). Our method of study is to reduce the interior transmission problem on [0, 1] to a problem of finding roots of a determinant of fundamental solutions to a Sturm–Liouville problem. The asymptotic expansion of solutions of the Sturm–Liouville problem then allows us to analyze properties of the transmission spectrum for large values of the wavenumber. (paper)

  10. Gear shift strategies for automotive transmissions

    NARCIS (Netherlands)

    Ngo, D.V.

    2012-01-01

    The development history of automotive engineering has shown the essential role of transmissions in road vehicles primarily powered by internal combustion engines. The engine with its physical constraints on the torque and speed requires a transmission to have its power converted to the drive power

  11. Transmission dynamics and resistance in staphylococci

    NARCIS (Netherlands)

    Hetem, D.J.

    2015-01-01

    This thesis will focus on nosocomial transmission and resistance of S. aureus and CoNS. After the general introduction on S. aureus and coagulase-negative staphylococci, part II focuses on the nosocomial transmission capacity of different MRSA clones in the hospital setting. In chapter 2 the

  12. Transmission : roadway to a competitive electricity market

    Energy Technology Data Exchange (ETDEWEB)

    Thon, S. [AltaLink L.P., AB (Canada)

    2002-07-01

    Having a variety of suppliers, marketers and retailers is the key to developing a successful electricity market which is more competitive on pricing, with less price volatility, more innovative customer products and higher levels of customer services. Some areas of Alberta are developing their own power markets with limited capacity to interact. These include Pincher Creek, Empress, Calgary, Edmonton, and Fort McMurray. It was noted that increasing transmission capacity is the key to ensuring a bigger and more competitive electricity market. Transmission constraints only encourage a small number of suppliers to control the market. The current cost of transmission capacity accounts for less than 5 per cent of an average residential customer's bill, but it plays a major role in providing more choice to competitive electricity suppliers. Developing more transmission capacity will create an even more competitive market that benefits both consumers and suppliers. Prices in Alberta have been very volatile in the past couple of years because of supply and demand issues, and there is a need to increase market liquidity. Alberta's Transmission Administrator is looking to expand the transmission network to alleviate constraints and to lower the cost of power generation, regardless of location. These expansions are not expected to affect customers' bills by more than 2 to 3 per cent. Such transmission concerns are being felt all over North America. The Federal Energy Regulatory Commission (FERC) in the United States also recognizes the link between transmission and creating a competitive electricity market.

  13. Elephant-to-Human Transmission of Tuberculosis

    Centers for Disease Control (CDC) Podcasts

    This podcast reports on the transmission of TB from elephants to humans. Dr. Rendi Murphree, Epidemic Intelligence Service Officer at the Centers for Disease Control and Prevention and Vanderbilt University Visiting Scholar, discusses the recent elephant-to-human transmission of tuberculosis at an elephant refuge in Tennessee.

  14. Current issues and strategies for transmission planning

    Energy Technology Data Exchange (ETDEWEB)

    Isaacs, A.L. [Electranix, Winnipeg, MB (Canada); Rajapakse, A. [Manitoba Univ., Winnipeg, MB (Canada)

    2008-07-01

    Following the widespread deregulation of the electric power industry in the early 1990s, significant changes occurred in the regulatory and planning environments of the industry. Several regions of North America remain fully or partially regulated in the traditional sense including most Canadian provinces, except for Alberta and Ontario. Although the Mexican system has separate generation and transmission companies and current restructuring efforts are underway, all companies are state-owned, and private investment in energy is heavily constrained by the Mexican constitution. In these regulated regions, traditional generation and transmission expansion planning methods remain in use. This paper presented an overview of current trends in transmission planning strategies that have evolved in response to the restructuring of the power industry, and a conceptual framework of a procedure that would guide planners faced with the challenges of incorporating large scale wind generation in deregulated environments. The paper provided background information on the effect of deregulation on transmission planning. Planning strategies that were discussed included quantifying risk to help identify best alternatives; use of reference systems to estimate generator costs and reduce uncertainty; project based transmission expansion; transmission construction ahead of generation; and generation ahead of transmission. The impact of wind on transmission planning as well as future work addressing challenges posed by wind were also addressed. Research is continuing in this area to illustrate the concepts proposed through a detailed case study. 15 refs., 2 figs.

  15. Wireless Transmission of Big Data: A Transmission Time Analysis over Fading Channel

    KAUST Repository

    Wang, Wen-Jing; Yang, Hong-Chuan; Alouini, Mohamed-Slim

    2018-01-01

    In this paper, we investigate the transmission time of a large amount of data over fading wireless channel with adaptive modulation and coding (AMC). Unlike traditional transmission systems, where the transmission time of a fixed amount of data is typically regarded as a constant, the transmission time with AMC becomes a random variable, as the transmission rate varies with the fading channel condition. To facilitate the design and optimization of wireless transmission schemes for big data applications, we present an analytical framework to determine statistical characterizations for the transmission time of big data with AMC. In particular, we derive the exact statistics of transmission time over block fading channels. The probability mass function (PMF) and cumulative distribution function (CDF) of transmission time are obtained for both slow and fast fading scenarios. We further extend our analysis to Markov channel, where transmission time becomes the sum of a sequence of exponentially distributed time slots. Analytical expression for the probability density function (PDF) of transmission time is derived for both fast fading and slow fading scenarios. These analytical results are essential to the optimal design and performance analysis of future wireless transmission systems for big data applications.

  16. Wireless Transmission of Big Data: A Transmission Time Analysis over Fading Channel

    KAUST Repository

    Wang, Wen-Jing

    2018-04-10

    In this paper, we investigate the transmission time of a large amount of data over fading wireless channel with adaptive modulation and coding (AMC). Unlike traditional transmission systems, where the transmission time of a fixed amount of data is typically regarded as a constant, the transmission time with AMC becomes a random variable, as the transmission rate varies with the fading channel condition. To facilitate the design and optimization of wireless transmission schemes for big data applications, we present an analytical framework to determine statistical characterizations for the transmission time of big data with AMC. In particular, we derive the exact statistics of transmission time over block fading channels. The probability mass function (PMF) and cumulative distribution function (CDF) of transmission time are obtained for both slow and fast fading scenarios. We further extend our analysis to Markov channel, where transmission time becomes the sum of a sequence of exponentially distributed time slots. Analytical expression for the probability density function (PDF) of transmission time is derived for both fast fading and slow fading scenarios. These analytical results are essential to the optimal design and performance analysis of future wireless transmission systems for big data applications.

  17. Peculiarities of Pattern Information Transmission

    Directory of Open Access Journals (Sweden)

    Evgeniy V. Yurkevich

    2017-01-01

    Full Text Available The rates of modern technologies development is such that educational programs are constantly required to be enlarged with new material. However, the introduced supplements often do not take into account the limited possibilities of perceiving amounts of information offered in class. As a result, a significant number of graduates get diplomas of educational institutions with a number of pathologies. Despite heavy load during training, the knowledge of a graduate is often not enough to recognize him ready to participate in modern production. The problem of providing quality education by creating a technology making it possible to maximize students’ knowledge while reducing the number of messages transmitted in the classroom. Consideration of the educational process in the form of an information system with messages transmitted in the form of images is proposed as one of the ways of solving it. The work assumed that each message is reflected in the consciousness of the source and receiver of information in the form of mental images. Mental images of the teacher and student are considered as a convolution of information. The analysis of peculiarities of mental images formation and development is given, a model of the mechanism of pattern information transmission is proposed. The model of transmitting sign, pattern, and symbol information is described. The communication bandwidth between the participants  of the educational process is considered as depending on their goal setting, training, physiological and emotional features, as well as a number of other non-formalized factors. Graduates of educational institutions are considered as means of producing intellectual products, and the purpose of obtaining knowledge is proposed to be formed based on the definition of the attractor of developing the “teacher-student” system. A principle of organizing educational processes is proposed: the education technology should not violate the consistency

  18. Gas transmission : a paradigm shift

    International Nuclear Information System (INIS)

    Cornelson, D.W.

    1997-01-01

    The evolution of energy markets in North America was discussed. The investment opportunities that are possible in a deregulated energy market, be it in production or in the generation of energy commodities, in the development of midstream infrastructure, or in the provision of energy services, were outlined. Deregulation of crude oil, natural gas and electricity has resulted in significant changes in the structure of energy markets and the way in which customers are served. One of the advantages of competition regarding power generation is that it has turned energy into a commodity which has resulted in greater customer choice and efficiency. As one example of midstream infrastructure development, the Alliance Pipeline project was described. This project was conceived as a means to enhance the value of western Canadian natural gas. The 1,900 mile pipeline will run from British Columbia, through Alberta into Chicago where it will interconnect with the North American gas transmission grid. The pipeline is an efficient means of transporting energy from Western Canada to North American markets, and Alliance, as a lowest cost transporter, will continue to put pressure on the traditional infrastructure to become even more competitive at the margin. As such, Alliance represents a paradigm shift in energy transportation, and serves as an excellent example of the type of investment opportunity that a deregulated market can provide. It was suggested that innovation and competition in a deregulated North American energy market will continue to increase. As electricity is deregulated, the energy market will respond more quickly to changes in supply and demand than it did in the past, in an effort to satisfy the needs of investors and customers. This will provide increased opportunities for restructuring and further competition

  19. Transmission policy in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Joskow, P.L. [Massachusetts Institute of Technology, Cambridge, MA (United States). Department of Economics

    2005-06-01

    This paper provides an overview of the development of electric power transmission access, pricing and investment policies in the US over the last 15 years and evaluates the current state of those policies. Pre-liberalization transmission access and pricing policies are reviewed first since more recent policies have evolved from them. FERC's efforts to ensure that transmission owning utilities provide non-discriminatory access and pricing to wholesale transmission customers, culminating in Order 888 and 889 are discussed. These rules did not respond to problems created by a highly balkanized transmission system and only partially responded to problems caused by common ownership and operation of transmission networks with generating and marketing businesses in the same regions. These problems motivated FERC to seek to create Regional Transmission Organizations (RTO) meeting a long list of criteria related to governance, network operations, transmission pricing and investment as reflected in Order 2000. The slow pace of 'voluntary' reform following Order 2000 led FERC to issue a proposed Standard Market Design Rule (SMD) which provided more detailed prescriptions for wholesale market design, network operations, regional planning, resource adequacy, and transmission investment. The SMD rule confronted enormous resistance from groups of utilities and states that had not embraced an electricity sector liberalization agenda. However, many of the provisions of the SMD are being implemented by the RTOs and ISOs in the Northeast and Midwest. PJM's market rules and transmission pricing, planning and investment policies are reviewed as an articulation of FERC's RTO and SMD visions. (author)

  20. [Basic research on BSE transmission to people].

    Science.gov (United States)

    Bodemer, W; Kaup, F J

    2002-08-01

    Prion diseases of animal and man belong to neurological diseases with amyloidal deposition of the respective proteins. As to prion disease, the cellular prionprotein is in its abnormal isoform(s) an essential component of prionprotein aggregates found in affected tissue. In contrast to all neurodegenerative diseases like Morbus Alzheimer or Huntington's disease, prion diseases are transmissible. Therefore, prion diseases were designated Transmissible Spongiform Encephalopathies (TSE). The diseases are well known since decades. Scrapie was first described around 1750, a BSE case was reported in the 1850, most likely a misdiagnosis, and in 1920/1930 the human Creutzfeldt-Jakob disease (CJD) had been described. Transmission of CJD i.e. Kuru had been suspected in the early 1950s and erronously classified as slow virus disease. The CJD transmission posed a problem to humans when transplants from CJD cases were used for treatment. Fortunately, these iatrogenic transmissions remained limited. But with the advent of BSE and appearance of variant CJD cases in the UK and some places in Europe scientists suspected that transmission from cattle to man could have happened. From animal models we know of successful transmission via several routes. Species barriers do not completely prevent transmission. Rather transmission barriers might exist controlling individual susceptibility against prions. Modes of transmission, susceptibility for transmission, identification of receptor molecules as well as molecular mechanisms of the transmission process are intensely investigated. Current knowledge let us to assume that inapparent stages of prion infection pretend a (not existing) species barrier. This inapparent infection preceeds overt disease and, thus, most re-search focuses on the development of highly sensitive assay systems for detection of minute amounts of pathological prionprotein in suspected cases. Inapparence also should warn us to underestimate BSE or human vCJD cases; at

  1. Nipah virus transmission in a hamster model.

    Directory of Open Access Journals (Sweden)

    Emmie de Wit

    2011-12-01

    Full Text Available Based on epidemiological data, it is believed that human-to-human transmission plays an important role in Nipah virus outbreaks. No experimental data are currently available on the potential routes of human-to-human transmission of Nipah virus. In a first dose-finding experiment in Syrian hamsters, it was shown that Nipah virus was predominantly shed via the respiratory tract within nasal and oropharyngeal secretions. Although Nipah viral RNA was detected in urogenital and rectal swabs, no infectious virus was recovered from these samples, suggesting no viable virus was shed via these routes. In addition, hamsters inoculated with high doses shed significantly higher amounts of viable Nipah virus particles in comparison with hamsters infected with lower inoculum doses. Using the highest inoculum dose, three potential routes of Nipah virus transmission were investigated in the hamster model: transmission via fomites, transmission via direct contact and transmission via aerosols. It was demonstrated that Nipah virus is transmitted efficiently via direct contact and inefficiently via fomites, but not via aerosols. These findings are in line with epidemiological data which suggest that direct contact with nasal and oropharyngeal secretions of Nipah virus infected individuals resulted in greater risk of Nipah virus infection. The data provide new and much-needed insights into the modes and efficiency of Nipah virus transmission and have important public health implications with regards to the risk assessment and management of future Nipah virus outbreaks.

  2. Investigation of hydraulic transmission noise sources

    Science.gov (United States)

    Klop, Richard J.

    Advanced hydrostatic transmissions and hydraulic hybrids show potential in new market segments such as commercial vehicles and passenger cars. Such new applications regard low noise generation as a high priority, thus, demanding new quiet hydrostatic transmission designs. In this thesis, the aim is to investigate noise sources of hydrostatic transmissions to discover strategies for designing compact and quiet solutions. A model has been developed to capture the interaction of a pump and motor working in a hydrostatic transmission and to predict overall noise sources. This model allows a designer to compare noise sources for various configurations and to design compact and inherently quiet solutions. The model describes dynamics of the system by coupling lumped parameter pump and motor models with a one-dimensional unsteady compressible transmission line model. The model has been verified with dynamic pressure measurements in the line over a wide operating range for several system structures. Simulation studies were performed illustrating sensitivities of several design variables and the potential of the model to design transmissions with minimal noise sources. A semi-anechoic chamber has been designed and constructed suitable for sound intensity measurements that can be used to derive sound power. Measurements proved the potential to reduce audible noise by predicting and reducing both noise sources. Sound power measurements were conducted on a series hybrid transmission test bench to validate the model and compare predicted noise sources with sound power.

  3. Valuation anomalies for interconnector transmission rights

    International Nuclear Information System (INIS)

    McInerney, Celine; Bunn, Derek

    2013-01-01

    Whilst the acquisition of physical transmission interconnector rights between two or more electricity markets can be structured as spread options on the spot prices of electricity between connected markets, empirical evidence suggests that actual prices may be quite different. This raises issues for the valuation of transmission rights, particularly in the European context of market harmonisation, and the use of transmission rights with increasing levels of wind penetration. We examine the price differentials between the Irish and British electricity markets, where explicit transmission capacity auctions have been persistently undersubscribed and transmission rights acquired but not fully utilised. We find significant empirical indications that auction prices for transmission rights are undervalued against both arbitrage and spread option valuations. We also find significant power flows against the efficient price spread direction. A survey of a group of experts with an interest in trading power between Ireland and Britain inform a number of possible explanations for the apparent inefficiencies. These include ex-post pricing in the Irish market, intermittent wind and strategic behaviour by dominant firms. - Highlights: ► Valuation anomalies for transmission rights highlight lack of market integration. ► Exports constrained from market with ex post pricing and no hedging mechanisms. ► High start-up costs for balancing plant may deter exports from high wind regions. ► Deadband created by capacity payments based on flows versus availability

  4. Hysteresis in simulations of malaria transmission

    Science.gov (United States)

    Yamana, Teresa K.; Qiu, Xin; Eltahir, Elfatih A. B.

    2017-10-01

    Malaria transmission is a complex system and in many parts of the world is closely related to climate conditions. However, studies on environmental determinants of malaria generally consider only concurrent climate conditions and ignore the historical or initial conditions of the system. Here, we demonstrate the concept of hysteresis in malaria transmission, defined as non-uniqueness of the relationship between malaria prevalence and concurrent climate conditions. We show the dependence of simulated malaria transmission on initial prevalence and the initial level of human immunity in the population. Using realistic time series of environmental variables, we quantify the effect of hysteresis in a modeled population. In a set of numerical experiments using HYDREMATS, a field-tested mechanistic model of malaria transmission, the simulated maximum malaria prevalence depends on both the initial prevalence and the initial level of human immunity in the population. We found the effects of initial conditions to be of comparable magnitude to the effects of interannual variability in environmental conditions in determining malaria prevalence. The memory associated with this hysteresis effect is longer in high transmission settings than in low transmission settings. Our results show that efforts to simulate and forecast malaria transmission must consider the exposure history of a location as well as the concurrent environmental drivers.

  5. Modeling of Viral Aerosol Transmission and Detection

    KAUST Repository

    Khalid, Maryam; Amin, Osama; Ahmed, Sajid; Alouini, Mohamed-Slim

    2018-01-01

    The objective of this work is to investigate the spread mechanism of diseases in the atmosphere as an engineering problem. Among the viral transmission mechanisms that do not include physical contact, aerosol transmission is the most significant mode of transmission where virus-laden droplets are carried over long distances by wind. In this work, we focus on aerosol transmission of virus and introduce the idea of viewing virus transmission through aerosols and their transport as a molecular communication problem, where one has no control over transmission source but a robust receiver can be designed using nano-biosensors. To investigate this idea, a complete system is presented and end-toend mathematical model for the aerosol transmission channel is derived under certain constraints and boundary conditions. In addition to transmitter and channel, a receiver architecture composed of air sampler and Silicon Nanowire field effect transistor is also discussed. Furthermore, a detection problem is formulated for which maximum likelihood decision rule and the corresponding missed detection probability is discussed. At the end, simulation results are presented to investigate the parameters that affect the performance and justify the feasibility of proposed setup in related applications.

  6. Considering FACTS in Optimal Transmission Expansion Planning

    Directory of Open Access Journals (Sweden)

    K. Soleimani

    2017-10-01

    Full Text Available The expansion of power transmission systems is an important part of the expansion of power systems that requires enormous investment costs. Since the construction of new transmission lines is very expensive, it is necessary to choose the most efficient expansion plan that ensures system security with a minimal number of new lines. In this paper, the role of Flexible AC Transmission System (FACTS devices in the effective operation and expansion planning of transmission systems is examined. Effort was taken to implement a method based on sensitivity analysis to select the optimal number and location of FACTS devices, lines and other elements of the transmission system. Using this method, the transmission expansion plan for a 9 and a 39 bus power system was performed with and without the presence of FACTS with the use of DPL environment in Digsilent software 15.1. Results show that the use of these devices reduces the need for new transmission lines and minimizes the investment cost.

  7. Expression of BKCa channels and the modulatory ß-subunits in the rat and porcine trigeminal ganglion

    DEFF Research Database (Denmark)

    Wulf-Johansson, Helle; Hay-Schmidt, Anders; Poulsen, Asser Nyander

    2009-01-01

    Large conductance calcium-activated potassium (BK(Ca)) channels contribute to electrical impulses, proper signal transmission of information and regulation of neurotransmitter release. Migraine has been proposed to be a trigeminovascular disease involving the sensory trigeminal pathways and the c...

  8. Transmission delays in hardware clock synchronization

    Science.gov (United States)

    Shin, Kang G.; Ramanathan, P.

    1988-01-01

    Various methods, both with software and hardware, have been proposed to synchronize a set of physical clocks in a system. Software methods are very flexible and economical but suffer an excessive time overhead, whereas hardware methods require no time overhead but are unable to handle transmission delays in clock signals. The effects of nonzero transmission delays in synchronization have been studied extensively in the communication area in the absence of malicious or Byzantine faults. The authors show that it is easy to incorporate the ideas from the communication area into the existing hardware clock synchronization algorithms to take into account the presence of both malicious faults and nonzero transmission delays.

  9. Renewable Energy Zone (REZ) Transmission Planning Process

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Nathan [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-03-08

    A REZ is a geographical area that enables the development of profitable, cost-effective, grid-connected renewable energy (RE). The REZ Transmission Planning Process is a proactive approach to plan, approve, and build transmission infrastructure connecting REZs to the power system which helps to increase the share of solar, wind and other RE resources in the power system while maintaining reliability and economics, and focuses on large-scale wind and solar resources that can be developed in sufficient quantities to warrant transmission system expansion and upgrades.

  10. Transmission congestion management in the electricity market

    Science.gov (United States)

    Chen, Yue

    2018-04-01

    In this paper we mainly discuss how to optimize the arrangement to decrease the loss of each line when the power generation side of the system transmission congestion occurs in a safe and economical manner. We respectively set the adjust model if the transmission can be eliminated which can calculate the best scheme and safety margin model when transmission cannot be eliminated which is a multi-objective planning problem. We solve the two models on the condition of the load power demands are 982.4MW and 1052.8 MW by Lingo and get the optimal management scheme.

  11. Integrated approach to transmission services pricing

    International Nuclear Information System (INIS)

    Yu, C.W.; David, A.K.

    1999-01-01

    The paper presents an intuitively logical split between: (a) embedded, (b) operating, and (c) expansion cost based pricing and methodologies for implementation, for transmission services. A conceptually straightforward mechanism for the equitable allocation of transmission network embedded cost recovery based on capacity-use and reliability benefit is proposed, expansion cost is charged on a long-run marginal cost basis and finally, operating cost recovery is based on short-run marginal pricing. This is followed by co-ordinating these alternatives and integrating the pricing mechanisms to achieve appropriate price signals for bulk power users of transmission systems. (author)

  12. Methicillin-resistant Staphylococcus aureus transmission

    DEFF Research Database (Denmark)

    Andersen, Leif Percival; Nielsen, Xiaohui

    2015-01-01

    INTRODUCTION: Even though methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of nosocomial infections, it may often be difficult to evaluate the exact route of transmission. METHODS: In this study, we describe four cases of nosocomial transmission of MRSA in a hospital with a low...... increase the risk of contaminating hands, arms and the front of the uniform. Hand hygiene is therefore essential, but the use of protection gowns with long sleeves is also important in order to prevent transmission of MRSA. After culture of MRSA and implementation of specific precautions to prevent...

  13. AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT II, MECHANICAL TRANSMISSIONS.

    Science.gov (United States)

    Human Engineering Inst., Cleveland, OH.

    THIS MODULE OF A 25-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE OPERATION AND MAINTENANCE OF MECHANICAL TRANSMISSIONS USED ON DIESEL POWERED VEHICLES. TOPICS ARE (1) PURPOSE OF TRANSMISSIONS, (2) RATIO DIFFERENCE, (3) CONSTANT MESH TRANSMISSIONS, (4) FOUR-SPEED TRUCK TRANSMISSION POWER FLOW, AND (5) TRANSMISSION TROUBLESHOOTING.…

  14. Superconducting power transmission: the perils and promise

    Energy Technology Data Exchange (ETDEWEB)

    Forsyth, E B

    1976-06-01

    The development of bulk electricity transmission systems must be considered in the light of changing growth rates, increasing resistances to ehv overhead transmission and the tendency to concentrate generation in fewer sites. Helium-cooled or superconducting cables possess technical characteristics which will make them suitable as utility network components for power transmission over distances of ten to several hundred miles. These properties are illustrated by considering two applications in existing electrical networks. The first is a 43 mile system to transmit 4800 MVA and the second is a potential application under study in Pennsylvania to transmit 10,000 MVA over a distance of 350 miles or so. Helium-cooled versions of these transmission systems were designed to permit technical and economic evaluations. The major groups and institutions throughout the world engaged in the development of helium-cooled cables are listed and aspects of the technical approaches are briefly described.

  15. Depistage clinique des infections sexuellement transmissibles chez ...

    African Journals Online (AJOL)

    Depistage clinique des infections sexuellement transmissibles chez les personnes vivant avec le VIH suivies au Centre de Traitement Ambulatoire du Centre National Hospitalier Universitaire Hubert Koutoukou Maga de Cotonou.

  16. Prevalence of Human Immunodeficiency Virus Transmission among ...

    African Journals Online (AJOL)

    sex, and social status with the subjects served as control. Voluntary counseling ... to HIV antibody. Conclusions: Blood transfusion is still a risk factor for HIV transmission .... 1.6% documented by Al-Mahroos and Ebrahim[15] in Bahrain. Island.

  17. Feasibility study of wireless power transmission systems

    Science.gov (United States)

    Robinson, W. J., Jr.

    1968-01-01

    Wireless microwave or laser energy transfers power from a manned earth-orbiting central station to unmanned astronomical substations. More efficient systems are required for the microwave power transmission.

  18. ASSESSMENT OF LONG TRANSMISSION AND DIS SESSMENT ...

    African Journals Online (AJOL)

    eobe

    cost (AIC) methodology and marginal incremental ... ing, distribution planning, power system economics, long run marginal costing .... and distribution); gas transmission, water supply and ..... future decision making on possible investments.

  19. High Voltage Power Transmission for Wind Energy

    Science.gov (United States)

    Kim, Young il

    The high wind speeds and wide available area at sea have recently increased the interests on offshore wind farms in the U.S.A. As offshore wind farms become larger and are placed further from the shore, the power transmission to the onshore grid becomes a key feature. Power transmission of the offshore wind farm, in which good wind conditions and a larger installation area than an onshore site are available, requires the use of submarine cable systems. Therefore, an underground power cable system requires unique design and installation challenges not found in the overhead power cable environment. This paper presents analysis about the benefit and drawbacks of three different transmission solutions: HVAC, LCC/VSC HVDC in the grid connecting offshore wind farms and also analyzed the electrical characteristics of underground cables. In particular, loss of HV (High Voltage) subsea power of the transmission cables was evaluated by the Brakelmann's theory, taking into account the distributions of current and temperature.

  20. Transmission planning in a deregulated environment

    DEFF Research Database (Denmark)

    Xu, Zhao

    2006-01-01

    The worldwide trend for the deregulation of the electricity generation and transmission industries has led to dramatic changes in system operation and planning procedures. The optimum approach to transmission-expansion planning in a deregulated environment is an open problem especially when the r...... electricity market grid are performed. In addition, the proposed method is compared with a traditional planning method to further verify its effectiveness....... the responsibilities of the organisations carrying out the planning work need to be addressed. To date there is a consensus that the system operator and network manager perform the expansion planning work in a centralised way. However, with an increasing input from the electricity market, the objectives, constraints...... and approaches toward transmission planning should be carefully designed to ensure system reliability as well as meeting the market requirements. A market-oriented approach for transmission planning in a deregulated environment is proposed. Case studies using the IEEE 14-bus system and the Australian national...