Autonomic Neuroscience: Basic and Clinical RSS feed: Current Issue. The aim of the Journal is to stimulate, publish and disseminate original investigations on the autonomic nervous system: this includes the innervation of blood vessels and viscera, autonomic ganglia, efferent and afferent autonomic pathways, and autonomic nuclei and pathways in the central nervous system. The Editors will consider papers that deal with any aspect of the autonomic nervous system, including structure, physiology, pharmacology, biochemistry, development, evolution, ageing, behavioural aspects, integrative role and influence on emotional and physical states of the body. Interdisciplinary studies will be encouraged. Studies dealing with human pathology will be also welcome. The main types of contribution are full-length articles. These should be as concise as possible and should describe original research that materially advances knowledge of the autonomic nervous system. Short communications, book reviews and short review articles will be considered for publication. Electronic usage An increasing number of readers access the journal online via ScienceDirect, one of the world's most advanced web delivery systems for scientific, technical and medical information. Average monthly article downloads for this journal: 7,511* * Figure is an average based on full text articles downloaded monthly via ScienceDirect between July 2007 and June 2008. http://www.autneu-journal.com/?rss=yesElsevier Inc.en © 2009 Published by Elsevier Inc. All rights reserved. Autonomic Neuroscience: Basic and Clinical1566-07021531-216 February 2010 © 2009 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.autneu-journal.com/article/PIIS1566070209005797/abstract?rss=yesEditorial Board10.1016/S1566-0702(09)00579-7Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-XIFCIFChttp://www.autneu-journal.com/article/PIIS1566070209004305/abstract?rss=yesIt is evident from the rapidly rising numbers of publications on visceral afferents that this is an area of research that is receiving considerable attention. Why is this? On the one hand sensory neurobiology in general is a major growth area impacting on our understanding of the way individuals monitor and respond to the external environment through sight, sound, taste, touch and smell. On the other hand visceral sensory mechanisms are important for homeostasis and dysfunction in these mechanisms is a major cause of morbidity through conditions like irritable bowel syndrome and overactive bladder. A better understanding of these mechanisms is likely to result in novel approaches to treatment. This special issue provides a comprehensive and up-to-date overview of visceral sensory mechanisms describing a number of lines of investigation that are either in the process of identifying major advances, or will likely lead to them in the near future. These investigations have taken full advantage of state of the art methodology and draw increasingly on translational approaches that take advances in basic understanding into the clinic. Therefore the field of visceral afferents has come of age.PrefaceL. Ashley Blackshaw, David Grundy10.1016/j.autneu.2009.08.005Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X12http://www.autneu-journal.com/article/PIIS1566070209004196/abstract?rss=yesAbstract: Visceral afferents play a key role in neural circuits underlying the physiological function of visceral organs. They are responsible for the detection and transmission of a variety of visceral sensations (e.g. satiety, urge, discomfort and pain) from the viscera to the central nervous system. A comprehensive account of the different functional types of visceral sensory neurons would be invaluable in understanding how sensory dysfunction occurs and how it might be diagnosed and treated. Our aim was to explore the morphology of different nerve endings of visceral afferents within the gastrointestinal tract and urinary bladder and how the morphology of these nerve endings may relate to their functional properties. Morphological studies of mechanosensitive endings of visceral afferents to the gut and bladder correlated with physiological recordings have added a new dimension to our ability to distinguish different functional classes of visceral afferents.Structure–function relationship of sensory endings in the gut and bladderVladimir P. Zagorodnyuk, Simon J.H. Brookes, Nick J. Spencer10.1016/j.autneu.2009.07.018Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X311http://www.autneu-journal.com/article/PIIS156607020900424X/abstract?rss=yesAbstract: Vagal afferent nerves are essential for optimal neural regulation of visceral organs, but are not often considered important for their defense. However, there are well-defined subsets of vagal afferent nerves that have activation properties indicative of specialization to detect potentially harmful stimuli (nociceptors). This is clearly exemplified by the vagal bronchopulmonary C-fibers that are quiescent in healthy lungs but are readily activated by noxious chemicals and inflammatory molecules. Vagal afferent nerves with similar activation properties have been also identified in the esophagus and probably exist in other visceral tissues. In addition, these putative vagal nociceptors often initiate defensive reflexes, can be sensitized, and have the capacity to induce central sensitization. This set of properties is a characteristic of nociceptors in somatic tissues.Vagal afferent nerves with the properties of nociceptorsM. Kollarik, F. Ru, M. Brozmanova10.1016/j.autneu.2009.08.001Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X1220http://www.autneu-journal.com/article/PIIS1566070209004263/abstract?rss=yesAbstract: One of the most intriguing abilities of the gut is to function in isolation. This is possible because the gut's own nervous system, the enteric nervous system, contains the necessary elements to control reflex behaviors. Much progress has been made in identifying those neurons that encode mechanical or chemical stimuli. Thus, muscle behaviors in the small and large intestines depend on mechanosensitive neurons which encode a variety of mechanical stimuli, ranging from brief deformation of the neurons soma or processes to sustained tissue stretch. Mechanosensitivity has been recorded in a wide variety of neurons which behave like rapid or slowly adapting mechanosensors. Strikingly, mechanosensitive neurons do not appear to belong to a distinct class of highly specialised neurons but rather differ in their electrophysiology, neurochemistry and morphology. While some mechanosensitive neurons may respond to one stimulus type others appear to be polymodal. Available data would suggest that mechanosensitive enteric neurons are multitasking and hence belong to multifunctional circuits. This review summarises the main arguments in favour of this concept, discusses the stimulus modalities, the response patterns and the functional role of mechanosensitive enteric neurons and concludes with identifying future challenges.Multifunctional mechanosensitive neurons in the enteric nervous systemMichael Schemann, Gemma Mazzuoli10.1016/j.autneu.2009.08.003Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X2125http://www.autneu-journal.com/article/PIIS1566070209004056/abstract?rss=yesAbstract: Sensory nerves of the urinary bladder consist of small diameter Aδ and C fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. Electrophysiological recordings in vitro and in vivo have revealed several distinct classes of afferent fibers that may signal a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The exact mechanisms that underline mechanosensory transduction in bladder afferent terminals remain ambiguous; however, a wide range of ion channels (e.g., TTX-resistant Na+ channels, Kv channels and hyperpolarization-activated cyclic nucleotide-gated cation channels) and receptors (e.g., TRPV1, TRPM8, TRPA1, P2X2/3, etc) have been identified at bladder afferent terminals and implicated in the generation and modulation of afferent signals. Experimental investigations have revealed that expression and/or function of these ion channels and receptors may be altered in animal models and patients with overactive and painful bladder disorders. Some of these ion channels and receptors may be potential therapeutic targets for bladder diseases.Ion channel and receptor mechanisms of bladder afferent nerve sensitivityBiying Sun, Qian Li, Li Dong, Weifang Rong10.1016/j.autneu.2009.07.003Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X2632http://www.autneu-journal.com/article/PIIS1566070209004020/abstract?rss=yesAbstract: Beyond serving as a simple barrier, there is growing evidence that the urinary bladder urothelium exhibits specialized sensory properties and play a key role in the detection and transmission of both physiological and nociceptive stimuli. These urothelial cells exhibit the ability to sense changes in their extracellular environment including the ability to respond to chemical, mechanical and thermal stimuli that may communicate the state of the urothelial environment to the underlying nervous and muscular systems. Here, we review the specialized anatomy of the urothelium and speculate on possible communication mechanisms from urothelial cells to various cell types within the bladder wall.Urothelial signalingLori A. Birder10.1016/j.autneu.2009.07.005Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X3340http://www.autneu-journal.com/article/PIIS1566070209004111/abstract?rss=yesAbstract: Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on a new data on endocrine cells in chemosensing in the GI tract, in particular on new findings on glucose-sensing by gut EEC cells and the importance of incretin peptides and vagal afferents in glucose homeostasis, on the role of G protein coupled receptors in gut chemosensing, and on the possibility that gut endocrine cells may be involved in the detection of a luminal constituent other than nutrients, the microbiota. The role of vagal afferent pathways as a downstream target of EEC cell products will be considered and, in particular, exciting new data on the plasticity of the vagal afferent pathway with respect to expression of receptors for GI hormones and how this may play a role in energy homeostasis will also be discussed.Gut chemosensing: Interactions between gut endocrine cells and visceral afferentsHelen E. Raybould10.1016/j.autneu.2009.07.007Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X4146http://www.autneu-journal.com/article/PIIS1566070209004251/abstract?rss=yesAbstract: The afferent innervation of the gastrointestinal (GI) tract consists of intrinsic and extrinsic sensory neurons that respond to nutrients, chemicals or mechanical stimuli within the gut lumen. Most stimuli do not interact directly with the afferent nerves but instead activate specialised cells in the epithelium in a process of sensory transduction. It is thought that one of the first steps in this process is the release of serotonin (5-HT) from the enterochromaffin (EC) cells. The EC cells are a sub-type of enteroendocrine (EE) cells which are found among the enterocytes of the intestinal epithelium. The EC cells are responsible for the production and storage of the largest pool of 5 HT in the body. Released 5-HT can act on the intrinsic nerves and vagal endings. This review will focus on the role of 5-HT in sensory transduction and examine how the EC cell produces and releases 5-HT. We will explore recent developments that have helped to elucidate some of the proteins that allow EC cells to sense the luminal environment. Finally, we will highlight some of the findings from new studies using electrochemical techniques which allow the real-time recording of 5-HT concentrations near to the EC cell.Serotonin release and uptake in the gastrointestinal tractPaul P. Bertrand, Rebecca L. Bertrand10.1016/j.autneu.2009.08.002Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X4757http://www.autneu-journal.com/article/PIIS1566070209004184/abstract?rss=yesAbstract: An organism's ability to perceive mechanical stimuli is vital in determining how it responds to environmental challenges. External mechanosensation is responsible for the senses of touch, hearing, proprioception and aspects of somatic pain. Internally, mechanosensation underlies the initiation of autonomic reflex control and all manner of visceral sensations including chronic pain. Despite our increased knowledge of the molecular identity of invertebrate proteins that convert mechanical stimuli into electrical signals, understanding the complete molecular basis of mammalian mechanotransduction is currently a major challenge. Although the number of candidate molecules that serve as mechanotransducers is ever increasing, debate currently rages as to whether or not they contribute directly or indirectly to mammalian mechanotransduction. Despite these controversies novel molecules have been identified and their contribution to mechanosensation, be it direct or indirect, have improved our understanding of the mechanisms underlying visceral mechanosensation. Moreover, they have provided potential new pharmacological strategies for the control of visceral pain.Molecular basis of mechanosensitivityStuart M. Brierley10.1016/j.autneu.2009.07.017Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X5868http://www.autneu-journal.com/article/PIIS1566070209004214/abstract?rss=yesAbstract: An essential property of visceral sensory afferents is to be able to alter their firing properties in response to changes in the microenvironment at the level of the sensory ending. Significant progress has been made in recent years in understanding the ionic mechanisms of the regulation of afferent neuronal excitability, and in identifying the mechanisms by which this can be altered. This article will review some of the recent developments in the state of knowledge regarding mechanisms of increased excitability after inflammation, and pharmacological modulation of excitability, concentrating on afferent nerves innervating the GI tract and urinary bladder.Visceral afferents — Determinants and modulation of excitabilityMichael J. Beyak10.1016/j.autneu.2009.07.019Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X6978http://www.autneu-journal.com/article/PIIS1566070209004202/abstract?rss=yesAbstract: Several weeks to several months after a bout of inflammation or an infectious event in a visceral organ, while inflammation or infection has resolved, defective nociceptive functions are sometimes still present, characterized by chronic pain symptoms, visceral hyperalgesia and allodynia. Visceral afferents which convey nociceptive messages have been shown to be hyperexcitable in inflammatory states. Only recently, studies have addressed visceral afferent electrical properties and neuroplastic changes in post-inflammatory situations. This review tries to appraise in post-inflammatory hypersensitive states, the most recent advances in the knowledge of visceral afferent inputs, together with in vivo recordings of visceral hyperalgesia and allodynia.Visceral afferents: What role in post-inflammatory pain?Nathalie Vergnolle10.1016/j.autneu.2009.07.015Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X7983http://www.autneu-journal.com/article/PIIS1566070209004032/abstract?rss=yesAbstract: Many forms of chronic pain are more prevalent in women and this is interpreted as the consequence of a direct role of estrogens in the modulation of pain perception. Some functional pain states, i.e. those without a clear and demonstrable pathology, are also more prevalent in women and the pain in these conditions is also modulated by hormonal variations during the menstrual cycle. Increased pain sensitivity is commonly interpreted as the consequence of peripheral or central hyperexcitability of nociceptive pathways. Therefore a role has been suggested for estrogen in the modulation of the excitability of nociceptive afferents and central neurons. The literature on the sign of this modulation is not uniform, with reports pointing to estrogen as either pro- or anti-nociceptive. In our hands, a permanent reduction in the levels of estrogen, such as that induced by surgical ovariectomy (OVX) generates a hyperalgesic state of slow onset and long duration that can be prevented or reversed by exogenous administration of estrogen. The hyperalgesia is characterized by mechanical and thermal hyperalgesia in the abdominal and pelvic regions as well as by visceral hypersensitivity. The possible role of estrogen in the prevention of chronic painful states is discussed.Estrogen-dependent changes in visceral afferent sensitivityRaul Sanoja, Fernando Cervero10.1016/j.autneu.2009.07.001Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X8489http://www.autneu-journal.com/article/PIIS156607020900410X/abstract?rss=yesAbstract: Recent progress in understanding visceral afferents, some of it reviewed in the present issue, serves to underscore how little is known about the aging of the visceral afferents in the gastrointestinal (GI) tract. In spite of the clinical importance of the issue—with age, GI function often becomes severely compromised—only a few initial observations on age-related structural changes of visceral afferents are available. Primary afferent cell bodies in both the nodose ganglia and dorsal root ganglia lose Nissl material and accumulate lipofucsin, inclusions, aggregates, and tangles. Additionally, in changes that we focus on in the present review, vagal visceral afferent terminals in both the muscle wall and the mucosa of the GI tract exhibit age-related structural changes. In aged animals, both of the vagal terminal types examined, namely intraganglionic laminar endings and villus afferents, exhibit dystrophic or regressive morphological changes. These neuropathies are associated with age-related changes in the structural integrity of the target organs of the affected afferents, suggesting that local changes in trophic environment may give rise to the aging of GI innervation. Given the clinical relevance of GI tract aging, a more complete understanding both of how aging alters the innervation of the gut and of how such changes might be mitigated should be made research priorities.Age-related changes in vagal afferents innervating the gastrointestinal tractRobert J. Phillips, Gary C. Walter, Terry L. Powley10.1016/j.autneu.2009.07.009Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X9098http://www.autneu-journal.com/article/PIIS1566070209004068/abstract?rss=yesAbstract: Multiple organs are targeted by the stress response, but the focus of this article is on stress-induced activation of visceral afferents in the gut. During recent years it became apparent that mast cells are pivotal in this response. Peripheral corticotrophin releasing factor (CRF) induces their degranulation whereupon mast cell mediators activate visceral afferents. In addition, these mediators are responsible for gut barrier dysfunction and subsequent influx of luminal antigens and bacteria. Some research groups have begun to investigate the possible importance of barrier dysfunction for enhanced visceral sensitivity. After reviewing the current knowledge on CRF-induced mast cell degranulation we will discuss these groundbreaking papers in a more elaborate way. They form the basis for a hypothesis in which not only CRF-induced but also antigen-mediated mast cell degranulation is relevant to stress-related afferent activation. Part of this hypothesis is certainly speculative and needs further investigation. At the end of this article we sum up some of the unanswered questions raised by others and during this review.Peripheral relays in stress-induced activation of visceral afferents in the gutRené M. van den Wijngaard, Tamira K. Klooker, Wouter J. de Jonge, Guy E. Boeckxstaens10.1016/j.autneu.2009.07.004Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X99105http://www.autneu-journal.com/article/PIIS1566070209004093/abstract?rss=yesAbstract: Viscero-somatic referral and sensitization has been well documented clinically and widely investigated, whereas viscero-visceral referral and sensitization (termed cross-organ sensitization) has only recently received attention as important to visceral disease states. Because second order neurons in the CNS have been extensively shown to receive convergent input from different visceral organs, it has been assumed that cross-organ sensitization arises by the same convergence-projection mechanism as advanced for viscero-somatic referral and sensitization. However, increasing evidence also suggests participation of peripheral mechanisms to explain referral and sensitization. We briefly summarize behavioral, morphological and physiological support of and focus on potential mechanisms underlying cross-organ sensitization.Visceral organ cross-sensitization — An integrated perspectiveP.R. Brumovsky, G.F. Gebhart10.1016/j.autneu.2009.07.006Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-X106115http://www.autneu-journal.com/article/PIIS1566070209005839/abstract?rss=yesNotes To Authors10.1016/S1566-0702(09)00583-9Autonomic Neuroscience: Basic and Clinical 153, 1 (2010)2010-02-16Autonomic Neuroscience: Basic and Clinical2010-02-161531-2S1566-0702(09)X0010-XII