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Physiological Research Mar 2020Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all... (Review)
Review
Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subservepruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Adelta nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.
Topics: Animals; Capsaicin; Cough; Histamine; Histamine Agonists; Humans; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Neurons, Afferent; Peripheral Nerves; Pruritus; Sensory Receptor Cells; Sensory System Agents
PubMed: 32228011
DOI: 10.33549/physiolres.934403 -
Cellular and Molecular Gastroenterology... 2023Gut functions including motility, secretion, and blood flow are largely controlled by the enteric nervous system. Characterizing the different classes of enteric neurons...
BACKGROUND AND AIMS
Gut functions including motility, secretion, and blood flow are largely controlled by the enteric nervous system. Characterizing the different classes of enteric neurons in the human gut is an important step to understand how its circuitry is organized and how it is affected by disease.
METHODS
Using multiplexed immunohistochemistry, 12 discriminating antisera were applied to distinguish different classes of myenteric neurons in the human colon (2596 neurons, 12 patients) according to their chemical coding. All antisera were applied to every neuron, in multiple layers, separated by elutions.
RESULTS
A total of 164 combinations of immunohistochemical markers were present among the 2596 neurons, which could be divided into 20 classes, with statistical validation. Putative functions were ascribed for 4 classes of putative excitatory motor neurons (EMN1-4), 4 inhibitory motor neurons (IMN1-4), 3 ascending interneurons (AIN1-3), 6 descending interneurons (DIN1-6), 2 classes of multiaxonal sensory neurons (SN1-2), and a small, miscellaneous group (1.8% of total). Soma-dendritic morphology was analyzed, revealing 5 common shapes distributed differentially between the 20 classes. Distinctive baskets of axonal varicosities surrounded 45% of myenteric nerve cell bodies and were associated with close appositions, suggesting possible connectivity. Baskets of cholinergic terminals and several other types of baskets selectively targeted ascending interneurons and excitatory motor neurons but were significantly sparser around inhibitory motor neurons.
CONCLUSIONS
Using a simple immunohistochemical method, human myenteric neurons were shown to comprise multiple classes based on chemical coding and morphology and dense clusters of axonal varicosities were selectively associated with some classes.
Topics: Humans; Myenteric Plexus; Enteric Nervous System; Neurons, Afferent; Motor Neurons; Colon
PubMed: 37355216
DOI: 10.1016/j.jcmgh.2023.06.010 -
Journal of Anatomy Aug 2015I present a brief review of current understanding of the innervation of the mammalian muscle spindle, from a personal historical perspective. The review begins with... (Review)
Review
I present a brief review of current understanding of the innervation of the mammalian muscle spindle, from a personal historical perspective. The review begins with comparative studies on the numbers of spindle afferents and considers how their relative abundance may best be assessed. This is followed by an examination of the distribution and some functional properties of the motor innervation. The primary ending is the subject of the final section, in particular, I look at what can be learned from serial sectioning and volumetric reconstruction, and present new results on a model and simulations concerning sensory terminal deformation during stretch.
Topics: Animals; Mammals; Motor Activity; Muscle Spindles; Muscle, Skeletal; Neurons, Afferent
PubMed: 26095428
DOI: 10.1111/joa.12297 -
Journal of Dental Research Aug 2022Dental pain is a persistent, detrimental public health issue that requires a better understanding of the mechanisms of tooth pain and inflammation in order to develop...
Dental pain is a persistent, detrimental public health issue that requires a better understanding of the mechanisms of tooth pain and inflammation in order to develop more effective treatments. Calcitonin gene-related peptide (CGRP) and dental pulp cells are promising candidates for mediating tooth pain and generating reparative dental tissues, respectively, but their behavior in the context of pulpitis remains elusive. The mouse incisor requires Sonic hedgehog (Shh) secreted from sensory nerves to continuously regenerate. However, it is unknown whether sensory nerves also regulate the comparatively nonregenerative mouse molar through CGRP and Shh. This is an important knowledge gap to fill since mouse incisors differ biologically from human teeth, while mouse and human molars are similar. In this work, we identified that molar pulp cells express CGRP receptor and Gli1, a Hedgehog (Hh) signaling protein found to label a dental stem cell population in the mouse incisor. We also observed in a mouse molar injury model that Hh signaling was activated and Shh expression was upregulated in vivo. We then determined in vitro that Shh and CGRP regulate differentiation of primary mouse molar and incisor pulp cells and a human dental pulp stem cell line. Furthermore, conditioned media from stimulated sensory neurons induced Hh signaling activation and inflammatory gene expression in primary molar pulp cells, which was abolished by inhibition of either Shh or CGRP. Our results suggest that CGRP and Shh signaling may promote an inflammatory response after injury in the molar and that activated sensory nerves secrete CGRP and Shh to regulate molar pulp cell expansion and differentiation into odontoblast-like cells for dentin repair. Thus, CGRP/Shh signaling should be considered for new strategies that seek to manage pain or dentin regeneration in the molar.
Topics: Animals; Calcitonin Gene-Related Peptide; Dental Pulp; Hedgehog Proteins; Humans; Incisor; Mice; Neurons, Afferent; Pain
PubMed: 35403480
DOI: 10.1177/00220345221086858 -
Autonomic Neuroscience : Basic &... May 2017The sympathetic nervous system has been identified as a major contributor to the pathophysiology of chronic heart failure (CHF) and other diseases such as hypertension... (Review)
Review
The sympathetic nervous system has been identified as a major contributor to the pathophysiology of chronic heart failure (CHF) and other diseases such as hypertension and diabetes, both in experimental animal models and patients. The kidneys have a dense afferent sensory innervation positioning it to be the origin of multimodal input to the central nervous system. Afferent renal nerve (ARN) signals are centrally integrated, and their activation results in a general increase in sympathetic tone, which is directed toward the kidneys as well as other peripheral organs innervated by the sympathetic nerves. In the central nervous system, stimulation of ARN increases the neuronal discharge frequency and neuronal activity in the paraventricular nucleus (PVN) of the hypothalamus. The activity of the neurons in the PVN is attenuated during iontophoretic application of glutamate receptor blocker, AP5. An enhanced afferent renal input to the PVN may be critically involved in dictating sympathoexcitation in CHF. Furthermore, renal denervation abrogates the enhanced neuronal activity within the PVN in rats with CHF, thereby possibly contributing to the reduction in sympathetic tone. Renal denervation also restores the decreased endogenous levels of neuronal nitric oxide synthase (nNOS) in the PVN of rats with CHF. Overall, these data demonstrate that sensory information originating in the kidney excites pre-autonomic sympathetic neurons within the PVN and this "renal-PVN afferent pathway" may contribute to elevated sympathetic nerve activity in hyper-sympathetic disease conditions such as CHF and hypertension.
Topics: Afferent Pathways; Animals; Humans; Kidney; Neurons, Afferent; Paraventricular Hypothalamic Nucleus; Sympathetic Nervous System
PubMed: 27527558
DOI: 10.1016/j.autneu.2016.08.008 -
Molecular Metabolism Oct 2017Metabolic viscera and their vasculature are richly innervated by peripheral sensory neurons. Here, we examined the metabolic and inflammatory profiles of mice with... (Review)
Review
OBJECTIVE AND METHODS
Metabolic viscera and their vasculature are richly innervated by peripheral sensory neurons. Here, we examined the metabolic and inflammatory profiles of mice with selective ablation of all Na1.8-expressing primary afferent neurons.
RESULTS
While mice lacking sensory neurons displayed no differences in body weight, food intake, energy expenditure, or body composition compared to controls on chow diet, ablated mice developed an exaggerated inflammatory response to high-fat feeding characterized by bouts of weight loss, splenomegaly, elevated circulating interleukin-6 and hepatic serum amyloid A expression. This phenotype appeared to be directly mediated by the ingestion of saturated lipids.
CONCLUSIONS
These data demonstrate that the Na1.8-expressing afferent neurons are not essential for energy balance but are required for limiting the acute phase response caused by an obesogenic diet.
Topics: Acute-Phase Reaction; Animals; Body Composition; Body Weight; Diet, High-Fat; Dietary Fats; Eating; Energy Metabolism; Homeostasis; Mice; NAV1.8 Voltage-Gated Sodium Channel; Neurons, Afferent; Obesity; Sensory Receptor Cells; Viscera; Weight Loss
PubMed: 29031710
DOI: 10.1016/j.molmet.2017.07.012 -
The Journal of Physiology Aug 2021The present study aimed to determine the sensory adaptation characteristics of hair cell ribbon synapses in vivo. Hair cells of the zebrafish lateral line transmit...
KEY POINTS
The present study aimed to determine the sensory adaptation characteristics of hair cell ribbon synapses in vivo. Hair cells of the zebrafish lateral line transmit hydrodynamic stimuli to the posterior lateral line ganglion afferent neurons. Excitatory hair bundle deflections by water-jet stimuli cause glutamate release at hair cell synapses with a rapid (phasic) and a sustained component, which are likely linked to the exocytosis of distinct vesicle pools. The glutamate-induced increase in afferent neuron firing rate adapts over time, which is mirrored by the depression of neurotransmitter release, without preventing phase-locking. Adaptation also occurs during inhibitory hair bundle displacements, highlighting a shift in the sensitivity range of the lateral line during prolonged stimulation. Postsynaptic mechanisms exert some degree of regulation on the afferent firing adaptation. We conclude that vesicle depletion is the primary determinant of firing rate adaptation, allowing lateral line hair cell ribbon synapses to maintain sensitivity to sustained stimuli.
ABSTRACT
Adaptation is used by sensory systems to adjust continuously their sensitivity to match changes in environmental stimuli. In the auditory and vestibular systems, the release properties of glutamate-containing vesicles at the hair cell ribbon synapses play a crucial role in sensory adaptation, thus shaping the neural response to sustained stimulation. How ribbon synapses regulate the release of glutamate and how they modulate afferent responses in vivo is still largely unknown. Here, we have used two-photon imaging and electrophysiology to investigate the synaptic transfer characteristics of the hair cells in the context of sensory adaptation in live zebrafish. Prolonged and repeated water-jet stimulation of the hair cell stereociliary bundles caused adaptation of the action potential firing rate elicited in the afferent neurons. By monitoring glutamate at ribbon synapses using time-lapse imaging, we identified two kinetically distinct release components: a rapid response that was exhausted within 50-100 ms and a slower and sustained response lasting the entire stimulation. After repeated stimulations, the recovery of the fast component followed a biphasic time course. Depression of glutamate release was largely responsible for the rapid firing rate adaptation recorded in the afferent neurons. However, postsynaptic Ca responses had a slower recovery time course compared to that of glutamate release, indicating that they are likely to contribute to the afferent firing adaptation. Hair cells also exhibited a form of adaptation during inhibitory bundle stimulations. We conclude that hair cells have optimised their synaptic machinery to encode prolonged stimuli and to maintain their sensitivity to new incoming stimuli.
Topics: Animals; Hair Cells, Auditory; Lateral Line System; Synapses; Synaptic Transmission; Zebrafish
PubMed: 34047358
DOI: 10.1113/JP281646 -
The Journal of Biological Chemistry Nov 2014Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded... (Review)
Review
Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded important insights into mechanisms of somatosensation, as well as other mechano-associated biologic processes such as sensing of shear stress, particularly in the vasculature, and regulation of urine flow and bladder distention. Other roles for Piezo proteins have emerged, some unexpected, including participation in cellular development, volume regulation, cellular migration, proliferation, and elongation. Mutations in human Piezo proteins have been associated with a variety of disorders including hereditary xerocytosis and several syndromes with muscular contracture as a prominent feature.
Topics: Amino Acid Sequence; Anemia, Hemolytic, Congenital; Animals; Electrophysiological Phenomena; Erythrocytes; Humans; Hydrops Fetalis; Ion Channels; Mice; Molecular Sequence Data; Mutation; Neurons, Afferent; Osteoclasts; Phylogeny; Protein Structure, Tertiary; Sequence Homology, Amino Acid
PubMed: 25305018
DOI: 10.1074/jbc.R114.612697 -
The European Journal of Neuroscience Mar 2019The dorsomedial striatum, a key site of reward-sensitive motor output, receives extensive afferent input from cortex, thalamus and midbrain. These projections are...
The dorsomedial striatum, a key site of reward-sensitive motor output, receives extensive afferent input from cortex, thalamus and midbrain. These projections are integrated by striatal microcircuits containing both spiny projection neurons and local circuit interneurons. To explore target cell specificity of these projections, we compared inputs onto D1-dopamine receptor-positive spiny neurons, parvalbumin-positive fast-spiking interneurons and somatostatin-positive low-threshold-spiking interneurons, using cell type-specific rabies virus tracing and optogenetic-mediated projection neuron recruitment in mice. While the relative proportion of retrogradely labelled projection neurons was similar between target cell types, the convergence of inputs was systematically higher for projections onto fast-spiking interneurons. Rabies virus is frequently used to assess cell-specific anatomical connectivity but it is unclear how this correlates to synaptic connectivity and efficacy. To test this, we compared tracing data with target cell-specific measures of synaptic efficacy for anterior cingulate cortex and parafascicular thalamic projections using novel quantitative optogenetic measures. We found that target-specific patterns of convergence were extensively modified according to region of projection neuron origin and postsynaptic cell type. Furthermore, we observed significant divergence between cell type-specific anatomical connectivity and measures of excitatory synaptic strength, particularly for low-threshold-spiking interneurons. Taken together, this suggests a basic uniform connectivity map for striatal afferent inputs upon which presynaptic-postsynaptic interactions impose substantial diversity of physiological connectivity.
Topics: Animals; Gyrus Cinguli; Interneurons; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neostriatum; Nerve Net; Neurons, Afferent; Optogenetics; Thalamus
PubMed: 29359830
DOI: 10.1111/ejn.13829 -
Frontiers in Immunology 2021Increased afferent input resulting from painful injury augments the activity of central nociceptive circuits both neuron-neuron and neuron-glia interactions. Microglia,...
Increased afferent input resulting from painful injury augments the activity of central nociceptive circuits both neuron-neuron and neuron-glia interactions. Microglia, resident immune cells of the central nervous system (CNS), play a crucial role in the pathogenesis of chronic pain. This study provides a framework for understanding how peripheral joint injury signals the CNS to engage spinal microglial responses. During the first week of monosodium iodoacetate (MIA)-induced knee joint injury in male rats, inflammatory and neuropathic pain were characterized by increased firing of peripheral joint afferents. This increased peripheral afferent activity was accompanied by increased Iba1 immunoreactivity within the spinal dorsal horn indicating microglial activation. Pharmacological silencing of C and A afferents with co-injections of QX-314 and bupivacaine, capsaicin, or flagellin prevented the development of mechanical allodynia and spinal microglial activity after MIA injection. Elevated levels of ATP in the cerebrospinal fluid (CSF) and increased expression of the ATP transporter vesicular nucleotide transporter (VNUT) in the ipsilateral spinal dorsal horn were also observed after MIA injections. Selective silencing of primary joint afferents subsequently inhibited ATP release into the CSF. Furthermore, increased spinal microglial reactivity, and alleviation of MIA-induced arthralgia with co-administration of QX-314 with bupivacaine were recapitulated in female rats. Our results demonstrate that early peripheral joint injury activates joint nociceptors, which triggers a central spinal microglial response. Elevation of ATP in the CSF, and spinal expression of VNUT suggest ATP signaling may modulate communication between sensory neurons and spinal microglia at 2 weeks of joint degeneration.
Topics: Adenosine Triphosphate; Animals; Arthralgia; Arthritis, Experimental; Disease Models, Animal; Female; Hyperalgesia; Iodoacetic Acid; Male; Microglia; Neurons, Afferent; Rats; Rats, Sprague-Dawley; Spinal Cord
PubMed: 33897685
DOI: 10.3389/fimmu.2021.626884