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1.
Elife ; 122024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742628

RESUMO

Peripheral neurons are heterogeneous and functionally diverse, but all share the capability to switch to a pro-regenerative state after nerve injury. Despite the assumption that the injury response is similar among neuronal subtypes, functional recovery may differ. Understanding the distinct intrinsic regenerative properties between neurons may help to improve the quality of regeneration, prioritizing the growth of axon subpopulations to their targets. Here, we present a comparative analysis of regeneration across four key peripheral neuron populations: motoneurons, proprioceptors, cutaneous mechanoreceptors, and nociceptors. Using Cre/Ai9 mice that allow fluorescent labeling of neuronal subtypes, we found that nociceptors showed the greater regeneration after a sciatic crush, followed by motoneurons, mechanoreceptors, and, finally, proprioceptors. By breeding these Cre mice with Ribotag mice, we isolated specific translatomes and defined the regenerative response of these neuronal subtypes after axotomy. Only 20% of the regulated genes were common, revealing a diverse response to injury among neurons, which was also supported by the differential influence of neurotrophins among neuron subtypes. Among differentially regulated genes, we proposed MED12 as a specific regulator of the regeneration of proprioceptors. Altogether, we demonstrate that the intrinsic regenerative capacity differs between peripheral neuron subtypes, opening the door to selectively modulate these responses.


Assuntos
Traumatismos dos Nervos Periféricos , Animais , Camundongos , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/metabolismo , Regeneração Nervosa/fisiologia , Neurônios Motores/fisiologia , Nociceptores/fisiologia , Nociceptores/metabolismo , Análise de Sequência de RNA , Mecanorreceptores/fisiologia , Mecanorreceptores/metabolismo , Axotomia , Masculino , Nervo Isquiático/lesões , Neurônios/fisiologia
2.
Pain ; 165(6): 1336-1347, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38739766

RESUMO

ABSTRACT: Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.


Assuntos
Modelos Animais de Doenças , Hiperalgesia , Mecanorreceptores , Camundongos Endogâmicos C57BL , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Camundongos , Hiperalgesia/fisiopatologia , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Mecanorreceptores/metabolismo , Mecanorreceptores/fisiologia , Masculino , Humanos , Limiar da Dor/fisiologia , Feminino , Medição da Dor , Camundongos Transgênicos , Neuralgia/etiologia , Neuralgia/metabolismo , Neuralgia/fisiopatologia
3.
Nat Commun ; 15(1): 2911, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575590

RESUMO

The roles of Aß low-threshold mechanoreceptors (LTMRs) in transmitting mechanical hyperalgesia and in alleviating chronic pain have been of great interest but remain contentious. Here we utilized intersectional genetic tools, optogenetics, and high-speed imaging to specifically examine functions of SplitCre labeled mouse Aß-LTMRs in this regard. Genetic ablation of SplitCre-Aß-LTMRs increased mechanical nociception but not thermosensation in both acute and chronic inflammatory pain conditions, indicating a modality-specific role in gating mechanical nociception. Local optogenetic activation of SplitCre-Aß-LTMRs triggered nociception after tissue inflammation, whereas their broad activation at the dorsal column still alleviated mechanical hypersensitivity of chronic inflammation. Taking all data into consideration, we propose a model, in which Aß-LTMRs play distinctive local and global roles in transmitting or alleviating mechanical hyperalgesia of chronic pain, respectively. Our model suggests a strategy of global activation plus local inhibition of Aß-LTMRs for treating mechanical hyperalgesia.


Assuntos
Dor Crônica , Hiperalgesia , Camundongos , Animais , Hiperalgesia/genética , Nociceptividade , Mecanorreceptores/fisiologia , Inflamação/genética
4.
Mol Pain ; 20: 17448069241240452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38438192

RESUMO

We recently used Nav1.8-ChR2 mice in which Nav1.8-expressing afferents were optogenetically tagged to classify mechanosensitive afferents into Nav1.8-ChR2-positive and Nav1.8-ChR2-negative mechanoreceptors. We found that the former were mainly high threshold mechanoreceptors (HTMRs), while the latter were low threshold mechanoreceptors (LTMRs). In the present study, we further investigated whether the properties of these mechanoreceptors were altered following tissue inflammation. Nav1.8-ChR2 mice received a subcutaneous injection of saline or Complete Freund's Adjuvant (CFA) in the hindpaws. Using the hind paw glabrous skin-tibial nerve preparation and the pressure-clamped single-fiber recordings, we found that CFA-induced hind paw inflammation lowered the mechanical threshold of many Nav1.8-ChR2-positive Aß-fiber mechanoreceptors but heightened the mechanical threshold of many Nav1.8-ChR2-negative Aß-fiber mechanoreceptors. Spontaneous action potential impulses were not observed in Nav1.8-ChR2-positive Aß-fiber mechanoreceptors but occurred in Nav1.8-ChR2-negative Aß-fiber mechanoreceptors with a lower mechanical threshold in the saline goup, and a higher mechanical threshold in the CFA group. No significant change was observed in the mechanical sensitivity of Nav1.8-ChR2-positive and Nav1.8-ChR2-negative Aδ-fiber mechanoreceptors and Nav1.8-ChR2-positive C-fiber mechanoreceptors following hind paw inflammation. Collectively, inflammation significantly altered the functional properties of both Nav1.8-ChR2-positive and Nav1.8-ChR2-negative Aß-fiber mechanoreceptors, which may contribute to mechanical allodynia during inflammation.


Assuntos
Mecanorreceptores , Pele , Camundongos , Animais , Pele/inervação , Hiperalgesia , Fibras Nervosas Amielínicas/fisiologia , Inflamação
5.
Nature ; 627(8005): 830-838, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448588

RESUMO

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.


Assuntos
Pulmão , Reflexo , Respiração , Mecânica Respiratória , Nervo Vago , Animais , Feminino , Masculino , Camundongos , Células Epiteliais/metabolismo , Pulmão/citologia , Pulmão/inervação , Pulmão/fisiologia , Mecanorreceptores/metabolismo , Parvalbuminas/metabolismo , Reflexo/fisiologia , Células Receptoras Sensoriais/metabolismo , Nervo Vago/fisiologia , Complacência Pulmonar/fisiologia , Mecânica Respiratória/fisiologia
6.
Nat Commun ; 15(1): 898, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320986

RESUMO

Previous work identified nociceptive Schwann cells that can initiate pain. Consistent with the existence of inherently mechanosensitive sensory Schwann cells, we found that in mice, the mechanosensory function of almost all nociceptors, including those signaling fast pain, were dependent on sensory Schwann cells. In polymodal nociceptors, sensory Schwann cells signal mechanical, but not cold or heat pain. Terminal Schwann cells also surround mechanoreceptor nerve-endings within the Meissner's corpuscle and in hair follicle lanceolate endings that both signal vibrotactile touch. Within Meissner´s corpuscles, two molecularly and functionally distinct sensory Schwann cells positive for Sox10 and Sox2 differentially modulate rapidly adapting mechanoreceptor function. Using optogenetics we show that Meissner's corpuscle Schwann cells are necessary for the perception of low threshold vibrotactile stimuli. These results show that sensory Schwann cells within diverse glio-neural mechanosensory end-organs are sensors for mechanical pain as well as necessary for touch perception.


Assuntos
Percepção do Tato , Tato , Camundongos , Animais , Tato/fisiologia , Nociceptividade , Percepção do Tato/fisiologia , Mecanorreceptores/fisiologia , Células de Schwann , Dor , Limiar Sensorial
7.
Elife ; 122024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386003

RESUMO

Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.


Assuntos
Proteínas de Homeodomínio , Fenômenos Fisiológicos do Sistema Nervoso , Fatores de Transcrição , Animais , Camundongos , Regulação da Expressão Gênica , Mecanorreceptores , Células Receptoras Sensoriais , Fatores de Transcrição/genética , Proteínas de Homeodomínio/genética
8.
Science ; 383(6686): 992-998, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422143

RESUMO

Touch perception is enabled by mechanically activated ion channels, the opening of which excites cutaneous sensory endings to initiate sensation. In this study, we identify ELKIN1 as an ion channel likely gated by mechanical force, necessary for normal touch sensitivity in mice. Touch insensitivity in Elkin1-/- mice was caused by a loss of mechanically activated currents (MA currents) in around half of all sensory neurons activated by light touch (low-threshold mechanoreceptors). Reintroduction of Elkin1 into sensory neurons from Elkin1-/- mice restored MA currents. Additionally, small interfering RNA-mediated knockdown of ELKIN1 from induced human sensory neurons substantially reduced indentation-induced MA currents, supporting a conserved role for ELKIN1 in human touch. Our data identify ELKIN1 as a core component of touch transduction in mice and potentially in humans.


Assuntos
Canais Iônicos , Mecanorreceptores , Mecanotransdução Celular , Proteínas de Membrana , Células Receptoras Sensoriais , Percepção do Tato , Animais , Humanos , Camundongos , Células HEK293 , Canais Iônicos/genética , Canais Iônicos/fisiologia , Mecanorreceptores/fisiologia , Mecanotransdução Celular/genética , Mecanotransdução Celular/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , RNA Interferente Pequeno , Tato , Camundongos Mutantes , Masculino , Feminino
9.
Bioinspir Biomim ; 19(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38306671

RESUMO

With increasing attention on the world's oceans, a significant amount of research has been focused on the sensing of marine-related parameters in recent years. In this paper, a bioinspired flow sensor with corrosion resistance, anti-interference capability, a portable design structure, easy integration, and directional sensing ability is presented to realize flow speed sensing in open water. The sensor is realized by a flexible artificial cupula that seals one side of an optical fiber acting as an artificial kinocilium. Below the artificial kinocilium, an encapsulated s-tapered optical fiber mimics the fish neuromast sensory mechanism and is supported by a 3D-printed structure that acts as the artificial supporting cell. To characterize the sensor, the optical transmission spectra of the sensory fiber under a set of water flow velocities and four orthogonal directions were monitored. The sensor's peak intensity responses were found to demonstrate flow sensing ability for velocity and direction, proving that this biomimetic portable sensing structure is a promising candidate for flow sensing in marine environments.


Assuntos
Biomimética , Fibras Ópticas , Animais , Água , Mecanorreceptores , Peixes
10.
Mol Pain ; 20: 17448069241226553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38172079

RESUMO

Ultraviolet B (UVB) radiation induces cutaneous inflammation, leading to thermal and mechanical hypersensitivity. Here, we examine the mechanical properties and profile of tactile and nociceptive peripheral afferents functionally disrupted by this injury and the role of oxytocin (OXT) as a modulator of this disruption. We recorded intracellularly from L4 afferents innervating the irradiated area (5.1 J/cm2) in 4-6 old week male mice (C57BL/6J) after administering OXT intraperitoneally, 6 mg/Kg. The distribution of recorded neurons was shifted by UVB radiation to a pattern observed after acute and chronic injuries and reduced mechanical thresholds of A and C- high threshold mechanoreceptors while reducing tactile sensitivity. UVB radiation did not change somatic membrane electrical properties or fiber conduction velocity. OXT systemic administration rapidly reversed these peripheral changes toward normal in both low and high-threshold mechanoreceptors and shifted recorded neuron distribution toward normal. OXT and V1aR receptors were present on the terminals of myelinated and unmyelinated afferents innervating the skin. We conclude that UVB radiation, similar to local tissue surgical injury, cancer metastasis, and peripheral nerve injury, alters the distribution of low and high threshold mechanoreceptors afferents and sensitizes nociceptors while desensitizing tactile units. Acute systemic OXT administration partially returns all of those effects to normal.


Assuntos
Nociceptividade , Ocitocina , Camundongos , Masculino , Animais , Ocitocina/farmacologia , Ocitocina/uso terapêutico , Camundongos Endogâmicos C57BL , Tato/fisiologia , Pele/inervação , Mecanorreceptores , Nociceptores/fisiologia
11.
Exp Physiol ; 109(1): 17-26, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-36869596

RESUMO

Proprioception is the sense that lets us perceive the location, movement and action of the body parts. The proprioceptive apparatus includes specialized sense organs (proprioceptors) which are embedded in the skeletal muscles. The eyeballs are moved by six pairs of eye muscles and binocular vision depends on fine-tuned coordination of the optical axes of both eyes. Although experimental studies indicate that the brain has access to eye position information, both classical proprioceptors (muscle spindles and Golgi tendon organ) are absent in the extraocular muscles of most mammalian species. This paradox of monitoring extraocular muscle activity in the absence of typical proprioceptors seemed to be resolved when a particular nerve specialization (the palisade ending) was detected in the extraocular muscles of mammals. In fact, for decades there was consensus that palisade endings were sensory structures that provide eye position information. The sensory function was called into question when recent studies revealed the molecular phenotype and the origin of palisade endings. Today we are faced with the fact that palisade endings exhibit sensory as well as motor features. This review aims to evaluate the literature on extraocular muscle proprioceptors and palisade endings and to reconsider current knowledge of their structure and function.


Assuntos
Músculos Oculomotores , Células Receptoras Sensoriais , Animais , Músculos Oculomotores/inervação , Músculos Oculomotores/fisiologia , Mecanorreceptores , Propriocepção/fisiologia , Fusos Musculares , Mamíferos
12.
J Anat ; 244(3): 468-475, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37946592

RESUMO

This study aims to quantitatively analyze the distribution of encapsulated nerve endings in the human thumb interphalangeal (IP) joint capsule. There are three types of nerve endings. Type-I nerve endings (Ruffini-like ending) sense pressure changes, Type II (Pacini-like ending) nerve endings contribute to the kinesthetic sense, and Type III (Golgi-like ending) nerve ending provides proprioceptive information. We dissected five right thumbs IP joints from freshly frozen cadavers (5 men). The mean age of the cadavers at the time of death was 63.4 years (55-73). Sections were stained with the hematoxylin-eosin and antiprotein gene product 9.5 (PGP9.5) to identify encapsulated nerve endings. Transverse sections were cut and divided into volar, dorsal, and then into two equal parts, proximal and distal. The density of encapsulated nerve endings compared to volar versus dorsal and proximal versus distal regions was examined. This study showed that type 1 nerve endings were more common in the distal parts of the IP joint (p < 0.05). Also, type 3 nerve endings were observed in the thumb IP joint. There was no difference between regions in type II and type III nerve endings. The current study demonstrates that the distribution of encapsulated nerve endings in the IP joint is different from the PIP and DIP joints. Moreover, further studies are required to understand the thumb's physiology.


Assuntos
Mecanorreceptores , Polegar , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Polegar/inervação , Mecanorreceptores/fisiologia , Articulações , Terminações Nervosas , Cadáver
13.
Adv Mater ; 36(9): e2305032, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37724482

RESUMO

The perception of object's deformability in unstructured interactions relies on both kinesthetic and cutaneous cues to adapt the uncertainties of an object. However, the existing tactile sensors cannot provide adequate cutaneous cues to self-adaptively estimate the material softness, especially in non-standard contact scenarios where the interacting object deviates from the assumption of an elastic half-infinite body. This paper proposes an innovative design of a tactile sensor that integrates the capabilities of two slow-adapting mechanoreceptors within a soft medium, allowing self-decoupled sensing of local pressure and strain at specific locations within the contact interface. By leveraging these localized cutaneous cues, the sensor can accurately and self-adaptively measure the material softness of an object, accommodating variations in thicknesses and applied forces. Furthermore, when combined with a kinesthetic cue from the robot, the sensor can enhance tactile expression by the synergy of two relevant deformation attributes, including material softness and compliance. It is demonstrated that the biomimetic fusion of tactile information can fully comprehend the deformability of an object, hence facilitating robotic decision-making and dexterous manipulation.


Assuntos
Biomimética , Robótica , Mecanorreceptores , Percepção
14.
Anat Histol Embryol ; 53(1): e12969, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37724616

RESUMO

The mammalian snout has Meissner's corpuscles (MCs), which transmit epicritic sensations as the animal explores its surroundings. To comprehend the somatosensory acuity in mammals, we examined the structural organization and density of bovine Meissner-like corpuscles (BMLCs) at various ages and compared the changes with other mammalian MCs. The skin from the snout of cows or oxen (2-11 years old) was obtained and processed through routine histological technique. Five-µm thick sections were prepared, silver stained according to the Bielschowsky technique as modified by Winkelman and Schmidt (Mayo Clinic Proceedings, 1957, 217), and observed under a compound light microscope quantitatively and qualitatively. The glabrous skin of the cow snout consisted of two types of BMLCs: One was a cylindrical or elongated structure found in the dermal papillae. The other type was spherical and developed in the superficial layers of the epidermis. BMLCs consisted of both coarse and fine nerve fibres. In the young, the corpuscle comprised thin nerve fibres with indistinct cell outlines. In adults, nerve fibres in the corpuscles were closely packed, and networks, varicosities and end bulbs were well developed. With advancing age, the MCs attenuated into a disorganized mass of nerve fibres. The bovine snout is a highly evolved somatosensory organ due to its rich nerve supply and functionally resembles the anthropoid fingertip. Somatosensory acuity will be lower in the glabrous bovine skin than in primate glabrous skin of the fingertip, as the nerve terminals within the BMLCs are less elaborate in content and structural complexity.


Assuntos
Mecanorreceptores , Pele , Feminino , Bovinos , Animais , Mecanorreceptores/fisiologia , Fibras Nervosas , Evolução Biológica , Mamíferos
15.
Exp Physiol ; 109(1): 45-54, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37417654

RESUMO

Proprioceptors are non-nociceptive low-threshold mechanoreceptors. However, recent studies have shown that proprioceptors are acid-sensitive and express a variety of proton-sensing ion channels and receptors. Accordingly, although proprioceptors are commonly known as mechanosensing neurons that monitor muscle contraction status and body position, they may have a role in the development of pain associated with tissue acidosis. In clinical practice, proprioception training is beneficial for pain relief. Here we summarize the current evidence to sketch a different role of proprioceptors in 'non-nociceptive pain' with a focus on their acid-sensing properties.


Assuntos
Dor Musculoesquelética , Humanos , Canais Iônicos Sensíveis a Ácido/fisiologia , Células Receptoras Sensoriais/fisiologia , Mecanorreceptores , Propriocepção/fisiologia
16.
Ann Anat ; 252: 152206, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154784

RESUMO

BACKGROUND: Afferent innervation of shoulder joints plays a fundamental role in nociception and mechanoception and its alteration result in shoulder´s disease that course with pain and functional disability. METHODS: Joints shoulder from healthy subjects (n = 20) and with chronic pain shoulder syndromes (n = 17) were analyzed using immunohistochemistry for S100 protein to identify nerve structures (nerve fibers and sensory corpuscles), coupled with a quantification of the sensory formations. Sensory nerve formations were quantified in 13 distinct areas in healthy joint shoulder and in the available equivalent areas in the pathological joints. Statistical analyses were conducted to assess differences between healthy shoulder and pathological shoulder joint (p< 0.05). RESULTS: All analyzed structures, i.e., glenohumeral capsule, acromioclavicular capsule, the extraarticular structures (subcoracoid region and subacromio-subdeltoid bursa) and intraarticular structures (biceps brachii tendon and labrum articulare) are variably innervated except the extrinsic coracoacromial ligament, which was aneural. The afferent innervation of healthy human shoulder joints consists of free nerve endings, simple lamellar corpuscles and Ruffini's corpuscles. Occasionally, Golgi-Mazzoni's and Pacinian corpuscles were found. However, the relative density of each one varied among joints and/or the different zones within the same joint. As a rule, the upper half and anterior half of healthy glenohumeral capsules have a higher innervation compared to the lower and posterior respectably. On the other hand, in joints from subjects suffering chronic shoulder pain, a reduced innervation was found, involving more the corpuscles than free nerve endings. CONCLUSIONS: Our findings report a global innervation map of the human shoulder joints, especially the glenohumeral one, and this knowledge might be of interest for arthroscopic surgeons allowing to develop more selective and unhurt treatments, controlling the pain, and avoiding the loss of afferent innervation after surgical procedures. To the light of our results the postero-inferior glenohumeral capsular region seems to be the more adequate to be a surgical portal (surgical access area) to prevent nerve lesions.


Assuntos
Dor Crônica , Articulação do Ombro , Humanos , Articulação do Ombro/inervação , Ombro , Mecanorreceptores , Células Receptoras Sensoriais
17.
Ann Anat ; 252: 152200, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38109982

RESUMO

BACKGROUND: The cutaneous end organ complexes or cutaneous sensory corpuscles are specialized sensory organs associated to low-threshold mechanoreceptors. Mechano-gated proteins forming a part of ion channels have been detected in both the axon and terminal glial cells of Meissner corpuscles, a specific cutaneous end organ complex in the human glabrous skin. The main candidates to mechanotransduction in Meissner corpuscles are members of the Piezo family of cationic ion channels. PIEZO2 has been detected in the axon of these sensory structures whereas no data exists about the occurrence and cell localization of PIEZO1. METHODS: Skin samples (n = 18) from the palmar aspect of the distal phalanx of the first and second fingers were analysed (8 female and 10 males; age range 26 to 61 26-61 years). Double immunofluorescence for PIEZO1 and PIEZO2 together with axonal or terminal glial cell markers was captured by laser confocal microscopy, and the percentage of PIEZOs positive Meissner corpuscles was evaluated. RESULTS: MCs from human fingers showed variable morphology and degree of lobulation. Regarding the basic immunohistochemical profile, in all cases the axons were immunoreactive for neurofilament proteins, neuron specific enolase and synaptophysin, while the lamellar cells displayed strong S100P immunoreactivity. PIEZO1 was detected co-localizing with axonal markers, but never with terminal glial cell markers, in the 56% of Meissner corpuscles; weak but specific immunofluorescence was additionally detected in the epidermis, especially in basal keratinocytes. Similarly, PIEZO2 immunoreactivity was found restricted to the axon in the 85% of Meissner corpuscles. PIEZO2 positive Merkel cells were also regularly found. CONCLUSIONS: PIEZO1 and PIEZO2 are expressed exclusively in the axon of a subpopulation of human digital Meissner corpuscles, thus suggesting that not only PIEZO2, but also PIEZO1 may be involved in the mechanotransduction from low-threshold mechanoreceptors.


Assuntos
Mecanotransdução Celular , Corpúsculos de Pacini , Feminino , Humanos , Masculino , Canais Iônicos/metabolismo , Mecanorreceptores , Células de Merkel , Corpúsculos de Pacini/química , Pele/metabolismo , Adulto , Pessoa de Meia-Idade
18.
Sci Adv ; 9(51): eadj3003, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134286

RESUMO

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. We designed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill, an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release and yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, P < 0.0001) and minimized the weight gain rate (P < 0.05) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.


Assuntos
Obesidade , Estômago , Humanos , Animais , Suínos , Obesidade/terapia , Obesidade/metabolismo , Mecanorreceptores/metabolismo , Aumento de Peso , Nervo Vago/fisiologia
19.
Sci Rep ; 13(1): 21149, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036579

RESUMO

Spatial acuity is a fundamental property of any sensory system. In the case of the somatosensory system, the two-point discrimination (2PD) test has long been used to investigate tactile spatial resolution. However, the somatosensory system comprises three main mechanoreceptive channels: the slowly adapting channel (SA) responds to steady pressure, the rapidly adapting channel (RA) responds to low-frequency vibration, and the Pacinian channel (PC) responds to high-frequency vibration. The use of mechanical stimuli in the classical 2PD test means that previous studies on tactile acuity have primarily focussed on the pressure-sensitive channel alone, while neglecting other submodalities. Here, we used a novel ultrasound stimulation to systematically investigate the spatial resolution of the two main vibrotactile channels. Contrary to the textbook view of poor spatial resolution for PC-like stimuli, across four experiments we found that high-frequency vibration produced surprisingly good spatial acuity. This effect remained after controlling for interchannel differences in stimulus detectability and perceived intensity. Laser doppler vibrometry experiments confirmed that the acuity of the PC channel was not simply an artifact of the skin's resonance to high-frequency mechanical stimulation. Thus, PC receptors may transmit substantial spatial information, despite their sparse distribution, deep location, and large receptive fields.


Assuntos
Mecanorreceptores , Tato , Tato/fisiologia , Mecanorreceptores/fisiologia , Corpúsculos de Pacini/fisiologia , Vias Aferentes/fisiologia , Vibração
20.
J Morphol ; 284(11): e21654, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37856275

RESUMO

The neuromast is a sensory structure of the lateral line system in aquatic vertebrates, which consists of hair cells and supporting cells. Hair cells are mechanosensory cells, generally arranged with bidirectional polarity. Here, we describe a neuromast with hair cells arranged radially instead of bidirectionally in the first cranial neuromast of four teleost species: red seabream (Pagrus major), spotted halibut (Verasper variegatus), brown sole (Pseudopleuronectes herzensteini), and marbled sole (Pseudopleuronectes yokohamae). In these four species, this polarity was identified only in the first cranial neuromast, where it appeared at the rostral edge of the otic vesicle before hatching. We investigated the initial appearance and fate of this unique neuromast using scanning electron microscopy. We also assessed characteristics of radial neuromast pertaining to morphogenesis, development, and innervation using a vital fluorescent marker and immunohistochemistry in V. variegatus. The kinocilium initially appears at the center of each hair cell, then moves to its outer perimeter to form radial polarity by around 7 days postfertilization. However, hair cells arranged radially disappear about 15 days after hatching. This is followed by the appearance of bidirectionally arranged hair cells, indicating that polarity replacement from radial to bidirectional has occurred. In P. herzensteini, both afferent and efferent synapses between the nerve fibers and hair cells were observed by transmission electron microscopy, suggesting that radial neuromast is functional. Our discovery suggests that neuromasts with radial polarity could enable larval fish to assimilate multiaxial stimuli during this life stage, potentially assisting them in detecting small water vibrations or water pressure changes.


Assuntos
Sistema da Linha Lateral , Mecanorreceptores , Animais , Peixes , Crânio , Microscopia Eletrônica de Varredura , Água , Peixe-Zebra
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