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Biomolecules Jul 2023Periradicular tissues have a rich supply of peripheral afferent neurons, also known as nociceptive neurons, originating from the trigeminal nerve. While their primary... (Review)
Review
Periradicular tissues have a rich supply of peripheral afferent neurons, also known as nociceptive neurons, originating from the trigeminal nerve. While their primary function is to relay pain signals to the brain, these are known to be involved in modulating innate and adaptive immunity by initiating neurogenic inflammation (NI). Studies have investigated neuroanatomy and measured the levels of biomolecules such as cytokines and neuropeptides in human saliva, gingival crevicular fluid, or blood/serum samples in apical periodontitis (AP) to validate the possible role of trigeminal nociceptors in inflammation and tissue regeneration. However, the contributions of nociceptors and the mechanisms involved in the neuro-immune interactions in AP are not fully understood. This narrative review addresses the complex biomolecular interactions of trigeminal nociceptors with macrophages, the effector cells of the innate immune system, in the clinical manifestations of AP.
Topics: Humans; Nociceptors; Inflammation; Periapical Periodontitis; Pain; Macrophages
PubMed: 37627258
DOI: 10.3390/biom13081193 -
American Journal of Physiology. Renal... Mar 2020Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon... (Review)
Review
Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon after the cloning of the ASIC subunits, almost 20 yr ago, investigators began to use genetically modified mice to assess the role of these channels in physiological processes. These studies provide critical insights about the participation of ASICs in sensory processes, including mechanotransduction, chemoreception, and nociception. Here, we provide an extensive assessment of these findings and discuss the current gaps in knowledge with regard to the functions of ASICs in the peripheral nervous system.
Topics: Acid Sensing Ion Channels; Animals; Pain; Sensory Receptor Cells; Signal Transduction; Touch
PubMed: 31984789
DOI: 10.1152/ajprenal.00546.2019 -
Glia Jul 2021Astrocytes are indispensable for proper neuronal functioning. Given the diverse needs of neuronal circuits and the variety of tasks astrocytes perform, the perceived...
Astrocytes are indispensable for proper neuronal functioning. Given the diverse needs of neuronal circuits and the variety of tasks astrocytes perform, the perceived homogeneous nature of astrocytes has been questioned. In the spinal dorsal horn, complex neuronal circuitries regulate the integration of sensory information of different modalities. The dorsal horn is organized in a distinct laminar manner based on termination patterns of high- and low-threshold afferent fibers and neuronal properties. Neurons in laminae I (L1) and II (L2) integrate potentially painful, nociceptive information, whereas neurons in lamina III (L3) and deeper laminae integrate innocuous, tactile information from the periphery. Sensory information is also integrated by an uncharacterized network of astrocytes. How these lamina-specific characteristics of neuronal circuits of the dorsal horn are of functional importance for properties of astrocytes is currently unknown. We addressed if astrocytes in L1, L2, and L3 of the upper dorsal horn of mice are differentially equipped for the needs of neuronal circuits that process sensory information of different modalities. We found that astrocytes in L1 and L2 were characterized by a higher density, higher expression of GFAP, Cx43, and GLAST and a faster coupling speed than astrocytes located in L3. L1 astrocytes were more responsive to Kir4.1 blockade and had higher levels of AQP4 compared to L3 astrocytes. In contrast, basic membrane properties, network formation, and somatic intracellular calcium signaling were similar in L1-L3 astrocytes. Our data indicate that the properties of spinal astrocytes are fine-tuned for the integration of nociceptive versus tactile information.
Topics: Animals; Astrocytes; Mice; Neurons; Posterior Horn Cells; Spinal Cord; Spinal Cord Dorsal Horn
PubMed: 33694249
DOI: 10.1002/glia.23990 -
Journal of Neurophysiology Sep 2022Integrative functions of spinal interneurons are well recognized but the relative role of different interneuronal populations in this process continues to be... (Review)
Review
Integrative functions of spinal interneurons are well recognized but the relative role of different interneuronal populations in this process continues to be investigated. It therefore appeared useful to review the principles of integration of afferent information by the interneurons analyzed so far as these principles should apply also to those remaining to be analyzed. Considering the results of both functional and morphological studies of spinal interneurons and of the morphology and immunochemistry of afferent fibers that provide input to them, the following five basic principles of processing of afferent information by them will be outlined; ) afferent information of any origin is forwarded to several neuronal populations, ) information from any sources of input is distributed unevenly, ) input from several sources is integrated by individual neurons as well as by their populations, ) specific combinations of input are integrated by different neuronal populations, and ) afferent input to spinal interneurons is only one of the features distinguishing their functional populations. As the spinal neuronal organization and properties of neurons and afferent fibers in the so far investigated species (cat, rodents, and primates) have been found to resemble, future studies using molecular techniques in the mouse should allow the new data to integrate with those of the preceding studies and the principles outlined earlier as well as any new ones should apply also in humans.
Topics: Afferent Pathways; Animals; Humans; Interneurons; Mice; Neurons, Afferent; Spinal Cord
PubMed: 36043802
DOI: 10.1152/jn.00344.2022 -
Current Opinion in Neurobiology Jun 2022The muscle spindle (MS) provides essential sensory information for motor control and proprioception. The Group Ia and II MS afferents are low threshold slowly-adapting... (Review)
Review
The muscle spindle (MS) provides essential sensory information for motor control and proprioception. The Group Ia and II MS afferents are low threshold slowly-adapting mechanoreceptors and report both static muscle length and dynamic muscle movement information. The exact molecular mechanism by which MS afferents transduce muscle movement into action potentials is incompletely understood. This short review will discuss recent evidence suggesting that PIEZO2 is an essential mechanically sensitive ion channel in MS afferents and that vesicle-released glutamate contributes to maintaining afferent excitability during the static phase of stretch. Other mechanically gated ion channels, voltage-gated sodium channels, other ion channels, regulatory proteins, and interactions with the intrafusal fibers are also important for MS afferent mechanosensation. Future studies are needed to fully understand mechanosensation in the MS and whether different complements of molecular mediators contribute to the different response properties of Group Ia and II afferents.
Topics: Action Potentials; Ion Channels; Mechanoreceptors; Muscle Spindles; Neurons, Afferent; Proprioception
PubMed: 35430481
DOI: 10.1016/j.conb.2022.102542 -
PLoS Computational Biology Dec 2022Sensory information is conveyed by populations of neurons, and coding strategies cannot always be deduced when considering individual neurons. Moreover, information...
Sensory information is conveyed by populations of neurons, and coding strategies cannot always be deduced when considering individual neurons. Moreover, information coding depends on the number of neurons available and on the composition of the population when multiple classes with different response properties are available. Here, we study population coding in human tactile afferents by employing a recently developed simulator of mechanoreceptor firing activity. First, we highlight the interplay of afferents within each class. We demonstrate that the optimal afferent density to convey maximal information depends on both the tactile feature under consideration and the afferent class. Second, we find that information is spread across different classes for all tactile features and that each class encodes both redundant and complementary information with respect to the other afferent classes. Specifically, combining information from multiple afferent classes improves information transmission and is often more efficient than increasing the density of afferents from the same class. Finally, we examine the importance of temporal and spatial contributions, respectively, to the joint spatiotemporal code. On average, destroying temporal information is more destructive than removing spatial information, but the importance of either depends on the stimulus feature analyzed. Overall, our results suggest that both optimal afferent innervation densities and the composition of the population depend in complex ways on the tactile features in question, potentially accounting for the variety in which tactile peripheral populations are assembled in different regions across the body.
Topics: Humans; Action Potentials; Touch; Mechanoreceptors; Neurons; Neurons, Afferent
PubMed: 36477028
DOI: 10.1371/journal.pcbi.1010763 -
American Journal of Physiology.... Sep 2019The potential role of the intestinal microbiota in modulating visceral pain has received increasing attention during recent years. This has led to the identification of... (Review)
Review
The potential role of the intestinal microbiota in modulating visceral pain has received increasing attention during recent years. This has led to the identification of signaling pathways that have been implicated in communication between gut bacteria and peripheral pain pathways. In addition to the well-characterized impact of the microbiota on the immune system, which in turn affects nociceptor excitability, bacteria can modulate visceral afferent pathways by effects on enterocytes, enteroendocrine cells, and the neurons themselves. Proteases produced by bacteria, or by host cells in response to bacteria, can increase or decrease the excitability of nociceptive dorsal root ganglion (DRG) neurons depending on the receptor activated. Short-chain fatty acids generated by colonic bacteria are involved in gut-brain communication, and intracolonic short-chain fatty acids have pronociceptive effects in rodents but may be antinociceptive in humans. Gut bacteria modulate the synthesis and release of enteroendocrine cell mediators, including serotonin and glucagon-like peptide-1, which activate extrinsic afferent neurons. Deciphering the complex interactions between visceral afferent neurons and the gut microbiota may lead to the development of improved probiotic therapies for visceral pain.
Topics: Animals; Colon; Ganglia, Spinal; Gastrointestinal Microbiome; Humans; Microbiota; Neurons, Afferent; Visceral Pain
PubMed: 31290688
DOI: 10.1152/ajpgi.00052.2019 -
Peptides Nov 2020Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we... (Review)
Review
Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we highlight the effect of estrogens on food intake regulation and the latest literature on intracellular estrogen signaling. In addition, gut satiety hormones, such as cholecystokinin, glucagon-like peptide 1 and leptin are essential to regulate ingestive behaviors in the postprandial period. These peripheral signals are sensed by vagal afferent terminals in the gut wall and transmitted to the hindbrain axis. Here we 1. review the role of the vagus-hindbrain axis in response to gut satiety signals and 2. consider the potential synergistic effects of estrogens on gut satiety signals at the level of vagal afferent neurons and nuclei located in the hindbrain. Understanding the action of estrogens in gut-brain axis provides a potential strategy to develop estrogen-based therapies for metabolic diseases and emphasizes the importance of sex difference in the treatment of obesity.
Topics: Animals; Cholecystokinin; Eating; Energy Metabolism; Estrogens; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Leptin; Male; Neurons, Afferent; Receptors, Estrogen; Rhombencephalon; Satiety Response; Vagus Nerve
PubMed: 32860834
DOI: 10.1016/j.peptides.2020.170389 -
International Journal of Molecular... Mar 2021The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry... (Review)
Review
The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry site for peripheral information and the final output site for motor response, placing spinal circuits as paramount in mediating sensory responses and coordinating movement. This is partly accomplished through the activation of complex spinal microcircuits that gate afferent signals to filter extraneous stimuli from various sensory modalities and determine which signals are transmitted to higher order structures in the CNS and to spinal motor pathways. A mechanistic understanding of how inhibitory interneurons are organized and employed within the spinal cord will provide potential access points for therapeutics targeting inhibitory deficits underlying various pathologies including sensory and movement disorders. Recent studies using transgenic manipulations, neurochemical profiling, and single-cell transcriptomics have identified distinct populations of inhibitory interneurons which express an array of genetic and/or neurochemical markers that constitute functional microcircuits. In this review, we provide an overview of identified neural components that make up inhibitory microcircuits within the dorsal and ventral spinal cord and highlight the importance of inhibitory control of sensorimotor pathways at the spinal level.
Topics: Afferent Pathways; Animals; Anterior Horn Cells; Humans; Interneurons; Models, Neurological; Motor Neurons; Movement; Movement Disorders; Nerve Fibers; Nerve Tissue Proteins; Neural Inhibition; Neuropeptides; Posterior Horn Cells; Sensation; Sensation Disorders; Sensory Gating; Sensory Receptor Cells; Spinal Cord; Synapses
PubMed: 33800863
DOI: 10.3390/ijms22052667 -
F1000Research 2019In the last few years, single-cell profiling of taste cells and ganglion cells has advanced our understanding of transduction, encoding, and transmission of information... (Review)
Review
In the last few years, single-cell profiling of taste cells and ganglion cells has advanced our understanding of transduction, encoding, and transmission of information from taste buds as relayed to the central nervous system. This review focuses on new knowledge from these molecular approaches and attempts to place this in the context of previous questions and findings in the field. The individual taste cells within a taste bud are molecularly specialized for detection of one of the primary taste qualities: salt, sour, sweet, umami, and bitter. Transduction and transmitter release mechanisms differ substantially for taste cells transducing sour (Type III cells) compared with those transducing the qualities of sweet, umami, or bitter (Type II cells), although ultimately all transmission of taste relies on activation of purinergic P2X receptors on the afferent nerves. The ganglion cells providing innervation to the taste buds also appear divisible into functional and molecular subtypes, and each ganglion cell is primarily but not exclusively responsive to one taste quality.
Topics: Animals; Humans; Neurons; Signal Transduction; Taste; Taste Buds
PubMed: 32185015
DOI: 10.12688/f1000research.21099.1