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PAIN - Novel targets and new technologies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193943 Year: Pages: 95 DOI: 10.3389/978-2-88919-394-3 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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The problem of clinical pain management is complex and far-reaching, as it encompasses many different types of pain, such as arthritis, musculoskeletal conditions, neuropathic pain, and visceral pain. It is widely known that many of the well-established analgesic pathways are centrally based, involving spinal and supraspinal sites. However, pain can also be effectively controlled by peripheral pathways. The analgesics market is growing and the driving forces are the aging population and need for better therapeutic benefits. There are various analgesic products that are available that can be administered by various routes, yet research is active in identifying new technologies for better drug targeting and novel targets to gain improved therapeutic efficiency. This e-Book "PAIN - Novel targets and new technologies" has brought together experts in the field of pain at the physiological, pharmacological and pharmaceutical levels to discuss novel pain targets and new pain technologies across the various types of pain. This information is presented as novel research findings, short communications and review articles. The goal of this e-Book is to generate further collaborative discussion on the future and direction of pain therapies.

Neural circuits underlying emotion and motivation: Insights from optogenetics and pharmacogenetics

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195343 Year: Pages: 172 DOI: 10.3389/978-2-88919-534-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-12-10 11:59:06
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Application of optogenetic and pharmacogenetic tools to study the neural circuits underlying emotional valence, feeding, arousal and motivated behaviors has provided crucial insights into brain function. Expression of light sensitive proteins into specific neurons and subsequent stimulation by light (optogenetics) to control neuronal activity or expression of designer receptors exclusively activated by designer drugs (DREADD) in specific neuronal populations with subsequent activation or suppression of neuronal activity by an otherwise inert ligand (pharmacogenetics) provides control over defined elements of neural circuits. These novel tools have provided a more in depth understanding into several questions about brain function. These include: • Regulation of sleep-wake transition by the interaction of hypocretin neurons of lateral hypothalamus and nor adrenergic neurons of the locus coruleaus • Regulation of feeding by AGRP and POMC neurons in arcuate nucleus of the hypothalamus • Place preference and positive reinforcement by activation of DA neuron of VTA • Place aversion by activation of VTA GABA and lateral habenula neurons • Opposing influences on reinforcement by activation of D1 and D2 expressing medium spiny neurons of dorsal striatum and nucleus accumbens The list still grows... From cell type specific manipulations to signaling properties in the cell (Dietz et al 2012) with unprecedented temporal resolution, these tools revolutionize the exploration of pathways/connectivity. Recent years also witnessed the extension of applying these tools from studying emotional valence and motivated behavior to reactivation of memory. c-fos based genetic approaches allowed us to integrate light sensitive opsins or DREADD receptor into specific neurons that are activated by certain learning events (for example fear) (Garner et al 2012; Liu et al 2012). In this Research Topic, we welcome researchers to contribute original research articles, review articles, methods and commentary on topics utilizing optogenetic and pharmacogenetic tools to study the neural circuits underlying emotional valence, motivation, reinforcement and memory. We believe the Research Topic will shine light on various questions we have about brain function by using novel optogenetic and pharmacogenetic tools and will hopefully inspire ongoing research to overcome the hurdles of using these tools to advance clinical applications.

Brain Reward & Stress Systems in Addiction

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194575 Year: Pages: 184 DOI: 10.3389/978-2-88919-457-5 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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Addiction to drugs and alcohol is a dynamic and multi-faceted disease process in humans, with devastating health and financial consequences for the individual and society-at-large. In humans, drug and alcohol use disorders (i.e., abuse and dependence) are defined by clusters of behavioral symptoms that can be modeled to various degrees in animals. Hallmark behavioral symptoms associated with drug and alcohol dependence are compulsive drug use, loss of control during episodes of drug use, the emergence of a negative emotional state in the absence of the drug, and chronic relapse vulnerability during drug abstinence. The transition to drug dependence is defined by neuroadaptations in brain circuits that, in the absence of drugs, mediate a variety of critical behavioral and physiological processes including natural reward, positive and negative emotional states, nociception, and feeding. Chronic drug exposure during the transition to dependence spurs (1) within-systems changes in neural circuits that contribute to the acute rewarding effects of the drug and (2) recruitment of brain stress systems (neuroendocrine and extra-hypothalamic). There are substantial genetic contributions to the propensity to use and abuse drugs, and drug abuse is highly co-morbid with various other psychiatric conditions (e.g., anxiety disorders, major depressive disorder) that may precede or follow the development of drug use problems. Across drugs of abuse, there are overlapping and dissociable aspects of the behavioral and neural changes that define the transition to dependence. Even within a single drug, people abuse drugs for a variety of reasons. The picture is further complicated by the fact that humans often abuse more than one drug concurrently. Even in the face of these challenges, pre-clinical and clinical research is making exponential gains into understanding the neurobiology of drug addiction. With the advent of new technologies and their combination with traditional approaches, the field is able to ask and answer addiction-related research questions in increasingly sophisticated ways. Here, we hope to assemble a collection of articles that provide an up-to-the-moment snapshot of the prevailing empirical, theoretical and technical directions in the addiction research field. We encourage submissions from all investigators working to understand the neurobiology of addiction, especially as it pertains to reward and stress pathways in the brain.

Keywords

relapse --- reward --- stress --- pain --- alcohol --- Nicotine --- Heroin --- Methamphetamine

Chemokines and chemokine receptors in brain homeostasis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196166 Year: Pages: 124 DOI: 10.3389/978-2-88919-616-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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Virtually involved in all pathologies that present an inflammatory component, it is now evident that, in the central nervous system, chemokines and chemokine receptors possess pleiotropic properties beyond chemotaxis: costitutive brain expression of chemokines and their receptors on endothelial cells, but also on neurons and glia, suggests a role for such molecules in mediating homeostatic cross-talk between cells of the brain perenchyma. Cross-talk between neurons and glia is determinant to the establishment and maintenance of a brain enviroment that ensure normal function, and in particular glial cells are active players that respond to enviromental changes and act for the survival, growth, differentiation and repair of the nervous tissue: in this regard brain endogenous chemokines represent key molecules that play a role in brain development, neurogenesis, neurotransmission and neuroprotection. As important regulators of peripheral immune response, chemokines are molecules of the immune system that play a central role in coordinating communication between the nervous and the immune systems, in the context of infections and brain injury. Indeed, in phatological processes resulting from infections, brain trauma, ischemia and chronic neurodegenerative diseases, chemokines represent important neuroinflammatory mediators that drive leucocytes trafficking into the central nervous system, facilitating an immune response by targeting cells of the innate and adaptive immune system. The third edition of the international conference "Chemokines and Chemokine Receptors in the Nervous System", hold in Rome in October 2013, represented an exciting platform to promote discussion among researchers in different disciplines to understand the role of chemokines in brain homoestasis. This Frontiers Research Topic arises from this conference, and wants to be an opportunity to further discuss and highlight the importance of brain chemokines as key molecules that, not only grant the interplay between the immune and the nervous systems, but in addition drive modulatory functions on brain homeoastasis orchestrating neurons, microglia, and astrocytes communication.

Ca2+ and Ca2+-interlocked Membrane Guanylate Cyclase Modulation

Authors: --- --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195060 Year: Pages: 185 DOI: 10.3389/978-2-88919-506-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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The tale of cyclic GMP has been astonishing. Having overcome an initial disbelief, cyclic GMP has risen to its present eminence as a premium cellular signal transduction messenger of not only hormonal extracellular but also of the intracellular signals. This research topic focuses on the pathways and functions of membrane guanylate cyclases in different tissues of the body and their interplay with intracellular sensory signals where in many cases, cyclic GMP along with Ca2+ have taken on roles as synarchic co-messengers.

The frontiers of clinical research on transcranial direct current stimulation (tDCS) in Neuropsychiatry

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192878 Year: Pages: 210 DOI: 10.3389/978-2-88919-287-8 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Medicine (General)
Added to DOAB on : 2015-12-10 11:59:07
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Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that induces changes in cortical activity and excitability according to the parameters of stimulation. TDCS effects have been reported since the 1800s with the development of the galvanic cell, although more systematic research has been conducted only from 1950-1970 and then from 1998 onwards. At the present time, most tDCS studies have been conducted in healthy volunteers, proving the properties of tDCS as a technique that induces long-lasting, polarity-dependent changes on specific brain areas. In addition, some studies have applied tDCS in selected neuropsychiatric samples, as to investigate its therapeutic effects, obtaining mixed albeit mostly positive results. Using tDCS in clinical practice could bring enormous gains for the treatment of several neuropsychiatric disorders, as tDCS is a portable, non-expensive and straightforward therapy, being therefore a putative candidate as an add-on or substitutive therapy for pharmacological treatments. However, there is still a gap between tDCS basic and clinical research, as it is still unknown whether and how the potent neuromodulatory effects observed after one tDCS session can be carried over for several weeks; therefore proving that tDCS is also a reliable clinical tool. In addition, another gap is observed in tDCS translational research, as results obtained from experimental animal models might not be fully generalizable to neuropsychiatric disorders in humans. Thus, advancing basic and experimental tDCS research as well as tailoring the optimal parameters of stimulation represents the frontiers of tDCS use in neuropsychiatry. In this special edition, our aim is to gather studies that contribute to the proposal of using tDCS for the treatment and investigation of neuropsychiatric disorders. Desired studies include (but are not limited to) the following topics: (1) clinical trials using tDCS as a treatment for neuropsychiatric disorders. (2) original studies investigating optimal parameters for daily tDCS stimulation. (3) safety and tolerability of tDCS, including reports of unexpected and serious adverse effects. (4) comprehensive reviews of putative mechanisms of action of tDCS for neuropsychiatric disorders. (5) translational research, testing different protocols of stimulation in experimental animals. (6) modeling tDCS studies, including studies testing different tDCS devices and montages. (7) studies of cost-efficacy analysis. (8) development of appropriate study designs for tDCS. (9) development of novel employments of tDCS, such as portable, safe devices that allow domestic utilization. (10) development of more precise and focal tDCS devices. To conclude, our ultimate aim is to host studies that contribute to bridge findings from basic and experimental tDCS research with clinical practice, therefore accelerating tDCS use as a novel arsenal for treating neuropsychiatric disorders.

New Perspectives in Neurosteroids action: a Special Player Allopregnanolone

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195558 Year: Pages: 86 DOI: 10.3389/978-2-88919-555-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Early in the 80’s date the first observations on the existence of hormonal steroids that may be synthesized and act in the nervous system. In order to refer to these endogenous steroids, proved important to control both central and peripheral nervous system, it was proposed the term “neurosteroids” (NSs). Over the years, their importance in regulating the physiological functions of neuronal and glial cells increased progressively. These steroids can be involved in several pathophysiological conditions such as depression, anxiety, premenstrual syndrome (PMS), schizophrenia and Alzheimer disease. Among the different classes of NSs, the progestagens revealed particularly important. The progesterone metabolite 5a-pregnan-3a-ol-20-one, also named tetrahydroprogesterone or allopregnanolone (ALLO) was one of the first most important steroid that was originally shown to act as neurosteroid. ALLO is synthesized through the action of the 5aR-3a-HSD, which converts P into DHP and subsequently, via a bidirectional reaction, into ALLO. NSs exert complex effects in the nervous system through ‘classic’, genomic, and ‘non-classic’, non-genomic actions. ALLO displays a rapid ‘non-genomic’ effect, which mainly involves the potent modulation of the GABA type A (GABA-A) receptor function. Recently a membrane receptor has been identified as target for ALLO effects, i.e. the membrane progesterone receptors (mPRs) that are able to activate a signalling cascade through G protein dependent mechanisms. By these ways, ALLO is able to modulate several cell functions, acting as neurogenic molecule on neural progenitor cells, as well as by activating proliferation and differentiation of glial cells in the central and peripheral nervous system. In this topic, we review the most recent acquisitions in the field of neurosteroids, focusing our attention on ALLO because its effects on the physiology of neurons and glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues and for the treatment of neuropsychiatric disorders.

Vitamin D and Human Health

ISBN: 9783038420569 9783038420576 Year: Pages: 476 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-10-22 08:50:54
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Vitamin D research has expanded greatly over the last 10 years, with a more than two-fold increase in annual publications listed in Pubmed with the key word ‘vitamin D’ from 1675 in 2005 to 3953 in 2014. Part of this increase is due to research showing that vitamin D deficiency is associated with a wide range of diseases and health outcomes. Until the 1980s, the primary focus of vitamin D research (in combination with calcium supplementation) was on bone diseases. Since then, observational studies have linked vitamin D deficiency with increased risk of many diseases: both acute and chronic. This book contains publications on several of these disease groups linked to vitamin D deficiency.

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2015 (8)