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International Journal of Molecular... May 2022Currently, myofascial pain has become one of the main problems in healthcare systems. Research into its causes and the structures related to it may help to improve its... (Review)
Review
Currently, myofascial pain has become one of the main problems in healthcare systems. Research into its causes and the structures related to it may help to improve its management. Until some years ago, all the studies were focused on muscle alterations, as trigger points, but recently, fasciae are starting to be considered a new, possible source of pain. This systematic review has been conducted for the purpose of analyze the current evidence of the muscular/deep fasciae innervation from a histological and/or immunohistochemical point of view. A literature search published between 2000 and 2021 was made in PubMed and Google Scholar. Search terms included a combination of fascia, innervation, immunohistochemical, and different immunohistochemical markers. Of the 23 total studies included in the review, five studies were performed in rats, four in mice, two in horses, ten in humans, and two in both humans and rats. There were a great variety of immunohistochemical markers used to detect the innervation of the fasciae; the most used were Protein Gene Marker 9.5 (used in twelve studies), Calcitonin Gene-Related Peptide (ten studies), S100 (ten studies), substance P (seven studies), and tyrosine hydroxylase (six studies). Various areas have been studied, with the thoracolumbar fascia being the most observed. Besides, the papers highlighted diversity in the density and type of innervation in the various fasciae, going from free nerve endings to Pacini and Ruffini corpuscles. Finally, it has been observed that the innervation is increased in the pathological fasciae. From this review, it is evident that fasciae are well innerved, their innervation have a particular distribution and precise localization and is composed especially by proprioceptors and nociceptors, the latter being more numerous in pathological situations. This could contribute to a better comprehension and management of pain.
Topics: Animals; Fascia; Horses; Mechanoreceptors; Mice; Musculoskeletal Physiological Phenomena; Pain; Rats; Sensory Receptor Cells
PubMed: 35628484
DOI: 10.3390/ijms23105674 -
Neuron Oct 2020Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of...
Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of distinct receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that all somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor that is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that transcription factors induced early after peripheral nerve injury confer the cellular plasticity required for sensory neurons to transform into a regenerative state.
Topics: Activating Transcription Factor 3; Animals; Axons; Axotomy; Cellular Reprogramming; Crush Injuries; Ganglia, Spinal; Gene Expression Regulation; Lumbar Vertebrae; Mechanoreceptors; Mice; Nerve Regeneration; Neuralgia; Neuronal Plasticity; Nociceptors; Peripheral Nerve Injuries; RNA-Seq; Recovery of Function; Sciatic Nerve; Sensory Receptor Cells; Single-Cell Analysis; Spinal Nerves; Transcriptome
PubMed: 32810432
DOI: 10.1016/j.neuron.2020.07.026 -
Journal of Neurophysiology Aug 2019In addition to being a prerequisite for many activities of daily living, the ability to maintain steady upright standing is a relevant model to study sensorimotor... (Review)
Review
In addition to being a prerequisite for many activities of daily living, the ability to maintain steady upright standing is a relevant model to study sensorimotor integrative function. Upright standing requires managing multimodal sensory inputs to produce finely tuned motor output that can be adjusted to accommodate changes in standing conditions and environment. The sensory information used for postural control mainly arises from the vestibular system of the inner ear, vision, and proprioception. Proprioception (sense of body position and movement) encompasses signals from mechanoreceptors (proprioceptors) located in muscles, tendons, and joint capsules. There is general agreement that proprioception signals from leg muscles provide the primary source of information for postural control. This is because of their exquisite sensitivity to detect body sway during unperturbed upright standing that mainly results from variations in leg muscle length induced by rotations around the ankle joint. However, aging is associated with alterations of muscle spindles and their neural pathways, which induce a decrease in the sensitivity, acuity, and integration of the proprioceptive signal. These alterations promote changes in postural control that reduce its efficiency and thereby may have deleterious consequences for the functional independence of an individual. This narrative review provides an overview of how aging alters the proprioceptive signal from the legs and presents compelling evidence that these changes modify the neural control of upright standing.
Topics: Aging; Humans; Leg; Muscle Spindles; Postural Balance; Proprioception; Standing Position
PubMed: 31166819
DOI: 10.1152/jn.00067.2019 -
Cell Nov 2019Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive...
Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here, we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.
Topics: Agouti-Related Protein; Animals; Brain; Feeding Behavior; Gastrointestinal Tract; Genetic Markers; Genetic Phenomena; Mechanoreceptors; Mice; Sensory Receptor Cells; Vagus Nerve; Viscera
PubMed: 31730854
DOI: 10.1016/j.cell.2019.10.031 -
Nature Reviews. Neuroscience Sep 2021Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces... (Review)
Review
Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. These end organ structures comprise a range of non-neuronal cell types, which may themselves actively contribute to the transformation of tactile forces into neural impulses within the LTMR afferents. Although the mechanism and the site of transduction across end organs remain unclear, PIEZO2 has emerged as the principal mechanosensitive channel involved in light touch of the skin. Here we review the physiological properties of LTMR subtypes and discuss how features of their cutaneous end organ complexes shape subtype-specific tuning.
Topics: Animals; Humans; Mechanoreceptors; Skin; Touch
PubMed: 34312536
DOI: 10.1038/s41583-021-00489-x -
Cell Aug 2023The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology...
The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.
Topics: Ganglia, Spinal; Mechanoreceptors; Colon; Neurons; Skin
PubMed: 37541195
DOI: 10.1016/j.cell.2023.07.007 -
Neuron Jul 2023Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many...
Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.
Topics: Animals; Mice; Core Binding Factor Alpha 3 Subunit; Esophagus; Gastrointestinal Motility; Homeodomain Proteins; Mechanoreceptors; Neurons, Afferent; Sensory Receptor Cells; Stomach; Vagus Nerve
PubMed: 37192624
DOI: 10.1016/j.neuron.2023.04.025 -
Physiological Reviews Apr 2020The transient receptor potential ankyrin (TRPA) channels are Ca-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only... (Review)
Review
The transient receptor potential ankyrin (TRPA) channels are Ca-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This includes a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel and many other chemically unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat, and mechanical stimuli, and its function is modulated by multiple factors, including Ca, trace metals, pH, and reactive oxygen, nitrogen, and carbonyl species. TRPA1 is involved in acute and chronic pain as well as inflammation, plays key roles in the pathophysiology of nearly all organ systems, and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties, and complex regulation to its roles in multiple pathophysiological conditions.
Topics: Animals; Calcium Signaling; Channelopathies; Chemoreceptor Cells; Humans; Inflammation; Mechanoreceptors; Mechanotransduction, Cellular; Nociception; Nociceptors; Pain; Sensory Receptor Cells; TRPA1 Cation Channel; Thermoreceptors; Thermosensing
PubMed: 31670612
DOI: 10.1152/physrev.00005.2019 -
Cell May 2020Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and...
Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.
Topics: Animals; Cell Line; Cell Nucleus; Chromatin; Heterochromatin; Humans; Male; Mechanoreceptors; Mechanotransduction, Cellular; Mesenchymal Stem Cells; Mice; Stress, Mechanical
PubMed: 32302590
DOI: 10.1016/j.cell.2020.03.052 -
Neuron Oct 2023Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How...
Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How forces act on morphologically dissimilar mechanosensory end organs of the skin to gate the requisite mechanotransduction channel Piezo2 and excite mechanosensory neurons is not understood. Here, we report high-resolution reconstructions of the hair follicle lanceolate complex, Meissner corpuscle, and Pacinian corpuscle and the subcellular distribution of Piezo2 within them. Across all three end organs, Piezo2 is restricted to the sensory axon membrane, including axon protrusions that extend from the axon body. These protrusions, which are numerous and elaborate extensively within the end organs, tether the axon to resident non-neuronal cells via adherens junctions. These findings support a unified model for dynamic touch in which mechanical stimuli stretch hundreds to thousands of axon protrusions across an end organ, opening proximal, axonal Piezo2 channels and exciting the neuron.
Topics: Animals; Merkel Cells; Mechanotransduction, Cellular; Imaging, Three-Dimensional; Ion Channels; Mechanoreceptors; Mammals
PubMed: 37725982
DOI: 10.1016/j.neuron.2023.08.023