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INTRODUCTION: Sensory nerve endings transmit mechanical stimuli into afferent neural signals and form the basis of proprioception, giving rise to the self-perception of dynamic stability of joints. We aimed to analyze the three-dimensional structure of periarticular corpuscular sensory nerve endings in a carpal ligament to enhance our understanding of their microstructure. METHODS: Two dorsal parts of the scapholunate ligament were excised from two human cadaveric wrist specimens. Consecutive cryosections were stained with immunofluorescence markers protein S100B, neurotrophin receptor p75, protein gene product 9.5 (PGP 9.5), and 4',6-diamidino-2-phenylindole. Three-dimensional images of sensory nerve endings were obtained using confocal laser scanning microscopy, and subsequent analysis was performed using Imaris software. RESULTS: Ruffini endings were characterized by a PGP 9.5-positive central axon, with a median diameter of 4.63 µm and a median of 25 cells. The p75-positive capsule had a range in thickness of 0.94 µm and 15.5 µm, consisting of single to three layers of lamellar cells. Ruffini endings were significantly smaller in volume than Pacini corpuscles or Golgi-like endings. The latter contained a median of three intracorpuscular structures. Ruffini endings and Golgi-like endings presented a similar structural composition of their capsule and subscapular space. The central axon of Pacini corpuscles was surrounded by S100-positive cells forming the inner core which was significantly smaller than the outer core, which was immunoreactive for p75 and PGP 9.5. CONCLUSION: This study reports new data regarding the intricate outer and intracorpuscular three-dimensional morphology of periarticular sensory nerve endings, including the volume, number of cells, and structural composition. These results may form a basis to differ between normal and pathological morphological changes in periarticular sensory nerve endings in future studies.
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BACKGROUND: To determine whether sensory nerve conduction stimulus threshold measurements of the infraorbital nerve are able to differentiate horses with idiopathic trigeminal-mediated headshaking (i-TMHS) from healthy horses and from horses with secondary trigeminal-mediated headshaking (s-TMHS). In a prospective trial, headshaking horses were examined using a standardized diagnostic protocol, including advanced diagnostics such as computed tomography and 3-Tesla-magnetic resonance imaging (MRI), to differentiate s-TMHS from i-TMHS. Clinically healthy horses served as controls. Within this process, patients underwent general anesthesia, and the minimal sensory nerve conduction stimulus threshold (SNCT) of the infraorbital nerve was measured using a bipolar concentric needle electrode. Sensory nerve action potentials (SNAP) were assessed in 2.5-5 mA intervals. Minimal SNCT as well as additional measurements were calculated. RESULTS: In 60 horses, SNAP could be recorded, of which 43 horses had i-TMHS, six had suspected s-TMHS, three horses had non-facial headshaking, and eight healthy horses served as controls. Controls had a minimal SNCT ≥ 15 mA, whereas 14/43 horses with i-TMHS and 2/6 horses with s-TMHS showed a minimal SNCT ≤ 10 mA. Minimal SNCT ≤ 10 mA showed 100% specificity to distinguish TMHS from controls, but the sensitivity was only 41%. CONCLUSION: A minimal SNCT of the infraorbital nerve ≤ 10 mA was able to differentiate healthy horses from horses with TMHS. Nevertheless, a higher minimal SNCT did not exclude i-TMHS or s-TMHS and minimal SNCT does not distinguish s-TMHS from i-TMHS.
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Enfermedades de los Caballos , Conducción Nerviosa , Animales , Caballos , Enfermedades de los Caballos/diagnóstico , Femenino , Masculino , Conducción Nerviosa/fisiología , Cabeza , Estudios Prospectivos , Nervio Trigémino/fisiologíaRESUMEN
PURPOSE: Sensory nerve terminals are highly distributed in the cornea, and regulate ocular surface sensation and homeostasis in response to various endogenous and exogenous stimuli. However, little is known about mediators regulating the physiological and pathophysiological activities of corneal sensory nerves. The aim of this study was to investigate the presence of cholinergic regulation in sensory nerves in the cornea. METHODS: Localization of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (vAChT) was evaluated using western blotting and immunohistochemical analysis. The synthesis and liberation of acetylcholine from the cornea were assessed using corneal segments pre-incubated with [3H]choline. The responsiveness of corneal neurons and nerves to cholinergic drugs was explored using calcium imaging with primary cultures of trigeminal ganglion neurons and extracellular recording from corneal preparations in guinea pigs. RESULTS: ChAT, but not vAChT, was highly distributed in the corneal epithelium. In corneal segments, [3H] acetylcholine was synthesized from [3H]choline, and was also released in response to electrical stimuli. In cultured corneal neurons, the population sensitive to a transient receptor potential melastatin 8 (TRPM8) agonist exhibited high probability of responding to nicotine in a calcium imaging experiment. The firing frequency of cold-sensitive corneal nerves was increased by the application of nicotine, but diminished by an α4 nicotinic acetylcholine receptor antagonist. CONCLUSIONS: The corneal epithelium can synthesize and release acetylcholine. Corneal acetylcholine can excite sensory nerves via nicotinic receptors containing the α4 subunit. Therefore, corneal acetylcholine may be one of the important regulators of corneal nerve activity arranging ocular surface condition and sensation.
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Acetilcolina , Córnea , Receptores Nicotínicos , Animales , Acetilcolina/metabolismo , Acetilcolina/farmacología , Córnea/inervación , Córnea/metabolismo , Cobayas , Receptores Nicotínicos/metabolismo , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Western Blotting , Células Cultivadas , Masculino , Ganglio del Trigémino/metabolismo , Inmunohistoquímica , Colina O-Acetiltransferasa/metabolismo , Proteínas de Transporte Vesicular de Acetilcolina/metabolismoRESUMEN
Objective: Nerve conduction studies (NCS) in children remain technically challenging and depend on the cooperation of the child. Motor NCS are not compromised by analgosedation but data for sensory NCS are lacking. Here, we ask whether sensory NCS is influenced by analgosedation. We also compare the present data with NCS studies from the 1990s regarding anthropometric acceleration of the contemporary paediatric population. Methods: Sensory NCS of the median nerve and sural nerve were performed in 182 healthy subjects aged 1 to 18â¯years during general anaesthesia and in 47 of them without analgosedation. Results: Sensory NCS was not influenced by midazolam or propofol. The sensory nerve action potential (SNAP) amplitude and the nerve conduction velocity (NCV) of the sural nerve as well as the SNAP of the median nerve show no significant age dependence in age range 1-18â¯years. The sensory NCV of the median nerve increased age-dependent. Conclusions: In clinical practice, analgosedation can be used for diagnostic NCS. Sensory NCS data show no relevant secular trend over the last 30â¯years. Differences due to technical inconsistency predominate. Significance: Analgosedation can improve diagnostic quality of sensory NCS in children. Additionally, we provide sensory NCS values from a large pediatric cohort.
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BACKGROUND: Guillain-Barré syndrome (GBS) is a condition characterized by acute and progressive weakness that impacts the limbs, facial muscles, and bulbar muscles due to acute polyneuro-radiculopathy. Typically, an infection that results in immune-mediated nerve dysfunction is what starts the disease. Patients often encounter paresthesia or discomfort before progressing to muscle weakness, initially in the lower extremities (which may include some proximal components) and subsequently in the upper extremities. The features of polyneuropathy identified during electrophysiology tests, bolstered by evidence of acquired demyelination in the nerve conduction study (NCS), support the clinical diagnosis of GBS. In peripheral neuropathies, NCS often reveals abnormalities in nerve conduction parameters. A specific pattern observed in the sensory nerve conduction study (SNCS), referred to as "sural sparing," signifies that the sural nerve, located near the calf muscles, remains relatively unaffected compared to other sensory nerves. Very few studies have been conducted to investigate improvements in sensory nerve conduction (SNC) parameters before and after intravenous immunoglobulin (IVIG), offering limited clinical correlation for the recovery and prognosis of the disease. The study aimed to observe the NCS parameters of the sensory nerves in both the upper and lower limbs, before and after the infusion of IVIG. METHODOLOGY: This study was an observational investigation conducted in the neurophysiology laboratory of the Physiology Department at a rural medical college in central India. Fifty clinically diagnosed cases of GBS aged between 18 and 60 years were referred from the Department of Medicine to the Physiology Department for conducting the NCS. Basic sociodemographic information, along with clinical history, was collected. Subsequently, the RMS EMG EP Mark-II machine was employed to examine the sensory nerve action potentials (SNAPs), such as amplitude (in mV) and conduction velocity (in ms), of the sensory nerves in both the upper and lower limbs before and after IVIG infusion. The IVIG infusion occurs within one week of clinically diagnosing GBS. Following an initial NCS, a second NCS follow-up study was conducted one week after the IVIG infusion to analyze the changing trend in sensory nerves. RESULTS: Upon analysis, no significant correlation was observed between the pre- and post-IVIG SNAPs of the median and ulnar nerves. However, the sural nerve conduction velocity's p-value of 0.033 demonstrated statistical significance, suggesting that the sural nerve is comparatively spared, confirming sural sparing. However, the SNAP of the sensory nerves in GBS patients showed a significant improvement overall, and only NCS quantified the percentage of improvement. CONCLUSION: According to the study, the NCS of sensory nerves showed a positive change in the parameters examined before and after the infusion of IVIG. This underscores the timely intervention of GBS with IVIG, and conducting the sensory conduction study diligently will enhance knowledge about the recovery period. Additionally, it supports the treating physician in making informed interventions based on the results post-IVIG infusion. This enhancement in the sensory nerves can only be quantified through NCS.
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Somatosensory innervation of the oral cavity enables the detection of a range of environmental stimuli including minute and noxious mechanical forces. The trigeminal sensory neurons underlie sensation originating from the tooth. Prior work has provided important physiological and molecular characterization of dental pulp sensory innervation. Clinical dental experiences have informed our conception of the consequence of activating these neurons. However, the biological role of sensory innervation within the tooth is yet to be defined. Recent transcriptomic data, combined with mouse genetic tools, have the capacity to provide important cell-type resolution for the physiological and behavioral function of pulp-innervating sensory neurons. Importantly, these tools can be applied to determine the neuronal origin of acute dental pain that coincides with tooth damage as well as pain stemming from tissue inflammation (i.e., pulpitis) toward developing treatment strategies aimed at relieving these distinct forms of pain.
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Objective: Diabetic peripheral neuropathy (DPN), a complication of diabetes, is detected only in later stages. Medial plantar nerve (MPL) can identify earlier stages of neuropathy. We evaluated the correlation of MPL sensory nerve action potentials (SNAPs) and severity of DPN measured using the Toronto Clinical Neuropathy Score (TCNS). Methods: In this hospital-based, cross-sectional study, we recruited diabetic subjects referred for suspected DPN. Neuropathy was graded with TCNS. Sural nerve conduction studies were performed using standard techniques. MPL studies were conducted using the modified Ponsford technique. All evaluations were performed on Nihon Kohden (model MEB 9200K). Averaged MPL SNAP was correlated with TCNS using Pearson's correlation coefficient. To estimate a correlation of 0.4 with 80% power (P = 0.05), we needed 46 subjects. Linear regression was conducted to adjust for age, duration, and diabetic control. Receiver operating characteristic (ROC) curve analysis was performed to obtain the cutoff for MPL SNAP values using the Youden index. Results: Fifty-one subjects with a mean age of 53.5 years (8.7) and mean duration of diabetes of 10.2 years (7.2) were included. MPL SNAPs were recordable in 12 patients, and the mean amplitude was 5.15 (2.9) µV. There was correlation between MPL SNAP and TCNS (r = -0.43, P = 0.02). No confounding was seen. Use of MPL SNAP resulted in diagnosis of DPN in an additional six (11.8%) patients. The ROC curve suggested that MPL SNAP cutoff of 1.05 µV had an accuracy of 67% in identifying neuropathy as defined by TCNS. Conclusions: MPL SNAP has a moderate correlation with clinical score and identifies more diabetic neuropathy than sural nerve.
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Maxillofacial bone defects exhibit intricate anatomy and irregular morphology, presenting challenges for effective treatment. This study aimed to address these challenges by developing an injectable bioactive composite microsphere, termed D-P-Ak (polydopamine-PLGA-akermanite), designed to fit within the defect site while minimizing injury. The D-P-Ak microspheres biodegraded gradually, releasing calcium, magnesium, and silicon ions, which, notably, not only directly stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also activated sensory nerve cells to secrete calcitonin gene-related peptide (CGRP), a key factor in bone repair. Moreover, the released CGRP enhanced the osteogenic differentiation of BMSCs through epigenetic methylation modification. Specifically, inhibition of EZH2 and enhancement of KDM6A reduced the trimethylation level of histone 3 at lysine 27 (H3K27), thereby activating the transcription of osteogenic genes such as Runx2 and Osx. The efficacy of the bioactive microspheres in bone repair is validated in a rat mandibular defect model, demonstrating that peripheral nerve response facilitates bone regeneration through epigenetic modification. These findings illuminated a novel strategy for constructing neuroactive osteo-inductive biomaterials with potential for further clinical applications.
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Regeneración Ósea , Células Madre Mesenquimatosas , Microesferas , Osteogénesis , Animales , Ratas , Células Madre Mesenquimatosas/metabolismo , Regeneración Ósea/genética , Regeneración Ósea/efectos de los fármacos , Regeneración Ósea/fisiología , Osteogénesis/fisiología , Osteogénesis/genética , Diferenciación Celular , Desmetilación , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Cerámica , Histonas/metabolismo , Histonas/genética , Péptido Relacionado con Gen de Calcitonina/metabolismo , Péptido Relacionado con Gen de Calcitonina/genética , Masculino , Materiales Biocompatibles/metabolismoRESUMEN
BACKGROUND: Existing methods identify only ≈10 Aδ-fibers in human sensory nerves per recording. This study examines methods to increase the detection of Aδ-fibers. NEW METHOD: Two to 20 averages of 500 replicate responses to epidermal nerve stimulation are obtained. Pairs of different averages are constructed. Each pair is analyzed with algorithms applied to amplitude and frequency to detect replication of responses to stimulation as "simultaneous similarities in two averages" (SS2AVs) at ≥99.5th percentile of control. In a pair of averages the latencies of amplitude and frequency SS2AVs for the same response to stimulation may differ by ≤0.25â¯ms. Therefore, Aδ-fibers are identified by the 0.25â¯ms moving sum of SS2AV latencies of the pairs of averages. RESULTS: Increasing averages increases pairs of different averages and detection of Aδ-fibers: from 2 to 10 Aδ-fibers with two averages (one pair) to >50 Aδ-fibers with 12-20 averages (66-190 pairs). COMPARISON WITH EXISTING METHOD(S): Existing methods identify ≤10 Aδ-fibers in 10 averages/45 pairs with the medians of amplitude and frequency algorithms applied to all 45 pairs. This study identifies Aδ-fibers (i) by applying these algorithms at the 99.5th percentile of control, (ii) to each pair of averages and (iii) by the 0.25â¯ms sum of algorithm identified events (SS2AVs) in all pairs. These three changes significantly increase the detection of Aδ-fibers, e.g., in 10 averages/45pairs from 10 to 45. CONCLUSIONS: Three modifications of existing methods can increase the detection of Aδ-fibers to an amount suitable (>50 with ≥12 averages) for statistical comparison of different nerves.
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Fibras Nerviosas Mielínicas , Fibras Nerviosas Amielínicas , Humanos , Fibras Nerviosas Amielínicas/fisiología , Vías AferentesRESUMEN
Discogenic pain is associated with deep nerve ingrowth in annulus fibrosus tissue (AF) of intervertebral disc (IVD). To model AF nerve ingrowth, primary bovine dorsal root ganglion (DRG) micro-scale tissue units are spatially organised around an AF explant by mild hydrodynamic forces within a collagen matrix. This results in a densely packed multicellular system mimicking the native DRG tissue morphology and a controlled AF-neuron distance. Such a multicellular organisation is essential to evolve populational-level cellular functions and in vivo-like morphologies. Pro-inflammatory cytokine-primed AF demonstrates its neurotrophic and neurotropic effects on nociceptor axons. Both effects are dependent on the AF-neuron distance underpinning the role of recapitulating inter-tissue/organ anatomical proximity when investigating their crosstalk. This is the first in vitro model studying AF nerve ingrowth by engineering mature and large animal tissues in a morphologically and physiologically relevant environment. The new approach can be used to biofabricate multi-tissue/organ models for untangling pathophysiological conditions and develop novel therapies.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Animales , Bovinos , Colágeno , Neuronas , Ganglios EspinalesRESUMEN
Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
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Senescencia Celular , Osteoclastos , Animales , Ratones , Osteoclastos/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/fisiología , Senescencia Celular/efectos de los fármacos , Células Receptoras Sensoriales/efectos de los fármacos , Células Receptoras Sensoriales/fisiología , Células Receptoras Sensoriales/metabolismo , Modelos Animales de Enfermedad , Masculino , Factor de Crecimiento Nervioso/metabolismo , Factor de Crecimiento Nervioso/farmacología , Netrina-1/metabolismo , Netrina-1/genética , Ratones Endogámicos C57BLRESUMEN
The trigeminal nerve is the sensory afferent of the orofacial regions and divided into three major branches. Cell bodies of the trigeminal nerve lie in the trigeminal ganglion and are surrounded by satellite cells. There is a close interaction between ganglion cells via satellite cells, but the function is not fully understood. In the present study, we clarified the ganglion cells' three-dimensional (3D) localization, which is essential to understand the functions of cell-cell interactions in the trigeminal ganglion. Fast blue was injected into 12 sites of the rat orofacial regions, and ganglion cells were retrogradely labeled. The labeled trigeminal ganglia were cleared by modified 3DISCO, imaged with confocal laser-scanning microscopy, and reconstructed in 3D. Histograms of the major axes of the fast blue-positive somata revealed that the peak major axes of the cells innervating the skin/mucosa were smaller than those of cells innervating the deep structures. Ganglion cells innervating the ophthalmic, maxillary, and mandibular divisions were distributed in the anterodorsal, central, and posterolateral portions of the trigeminal ganglion, respectively, with considerable overlap in the border region. The intermingling in the distribution of ganglion cells within each division was also high, in particular, within the mandibular division. Specifically, intermingling was observed in combinations of tongue and masseter/temporal muscles, maxillary/mandibular molars and masseter/temporal muscles, and tongue and mandibular molars. Double retrograde labeling confirmed that some ganglion cells innervating these combinations were closely apposed. Our data provide essential information for understanding the function of ganglion cell-cell interactions via satellite cells.
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Amidinas , Ganglio del Trigémino , Nervio Trigémino , Ratas , Animales , Ganglio del Trigémino/fisiología , Neuronas , Neuronas AferentesRESUMEN
BACKGROUND: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values. METHODS: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed. RESULTS: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators. CONCLUSION: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aß fiber neuropathy.
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Cirrosis Hepática , Humanos , Femenino , Masculino , Persona de Mediana Edad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Cirrosis Hepática/sangre , Adulto , Estimulación Eléctrica , Anciano , Nervio Mediano/fisiopatología , Células Receptoras Sensoriales/fisiología , Umbral Sensorial/fisiología , Nervio Peroneo/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/sangre , Fibras Nerviosas/patología , Fibras Nerviosas/fisiologíaRESUMEN
Objective: The current research aimed to analyze the alterations within the motor cortex and pyramidal pathways and their association with the degree of damage within the peripheral nerve fibers in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). To achieve that goal, we investigated the microstructural changes within the pyramidal white matter tracts using diffusion tensor imaging (DTI) parameters, evaluated metabolic alterations in both precentral gyri using magnetic resonance spectroscopy (MRS) ratios, and correlated them with the neurographic findings in patients with CIDP. Methods: The spectroscopic ratios of NAA/Cr, Cho/Cr, and mI/Cr from both precentral gyri and the values of fractional anisotropy (FA), axial diffusivity (AD), and mean diffusivity (MD) from both of the corticospinal tracts were correlated with the results of neurological and neurographic findings. The comparison of DTI parameters between the patients and controls was performed using Student's t-test or the Mann-Whitney U test. Due to the lack of normal distribution of most variables, Spearman's Rho rank coefficient was used to test all correlations. All analyses were performed at a significant level of alpha = 0.05 using STATISTICA 13.3. Results: Compared to the control group (CG), the patient group showed significantly lower ratios of NAA/Cr (1.66 ± 0.11 vs. 1.61 ± 0.15; p = 0.022), higher ratios of ml/Cr in the right precentral gyrus (0.57 ± 0.15 vs. 0.61 ± 0.08; p = 0.005), and higher levels of Cho/Cr within the left precentral gyrus (0.83 ± 0.09 vs. 0.88 ± 0.14, p = 0.012). The DTI parameters of MD from the right CST and AD from the right and left CSTs showed a strong positive correlation (0.52-0.53) with the sural sensory nerve action potential (SNAP) latency of the right sural nerve. There were no other significant correlations between other DTI and MRS parameters and neurographic results. Significance: In our study, significant metabolic alterations were found in the precentral gyri in patients with CIDP without clinical symptoms of central nervous system involvement. The revealed changes reflected neuronal loss or dysfunction, myelin degradation, and increased gliosis. Our results suggest coexisting CNS damage in these patients and may provide a new insight into the still unknown pathomechanism of CIDP.
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[This corrects the article DOI: 10.3389/fneur.2023.1259887.].
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We developed a rat dorsal root ganglion (DRG)-derived sensory nerve organotypic model by culturing DRG explants on an organoid culture device. With this method, a large number of organotypic cultures can be produced simultaneously with high reproducibility simply by seeding DRG explants derived from rat embryos. Unlike previous DRG explant models, this organotypic model consists of a ganglion and an axon bundle with myelinated A fibers, unmyelinated C fibers, and stereo-myelin-forming nodes of Ranvier. The model also exhibits Ca2+ signaling in cell bodies in response to application of chemical stimuli to nerve terminals. Further, axonal transection increases the activating transcription factor 3 mRNA level in ganglia. Axons and myelin are shown to regenerate 14 days following transection. Our sensory organotypic model enables analysis of neuronal excitability in response to pain stimuli and tracking of morphological changes in the axon bundle over weeks.
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Axones , Ganglios Espinales , Animales , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Ratas , Axones/fisiología , Axones/metabolismo , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Ratas Sprague-Dawley , Nervios Periféricos/metabolismo , Organoides/metabolismo , Señalización del Calcio , Vaina de Mielina/fisiología , Vaina de Mielina/metabolismo , Sistemas Microfisiológicos , Factor de Transcripción Activador 3RESUMEN
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.
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Dolor Crónico , Articulación del Hombro , Humanos , Articulación del Hombro/inervación , Hombro , Mecanorreceptores , Células Receptoras SensorialesRESUMEN
Respiratory viral infection can lead to activation of sensory afferent nerves as indicated by the consequential sore throat, sneezing, coughing, and reflex secretions. In addition to causing troubling symptoms, sensory nerve activation likely accelerates viral spreading. The mechanism how viruses activate sensory nerve terminals during infection is unknown. In this study, we investigate whether coronavirus spike protein activates sensory nerves terminating in the airways. We used isolated vagally-innervated mouse trachea-lung preparation for two-photon microscopy and extracellular electrophysiological recordings. Using two-photon Ca2+ imaging, we evaluated a total number of 786 vagal bronchopulmonary nerves in six experiments. Approximately 49% of the sensory fibers were activated by S1 protein (4 µg/mL intratracheally). Extracellular nerve recording showed the S1 protein evoked action potential discharge in sensory C-fibers; of 39 airway C-fibers (one fiber per mouse), 17 were activated. Additionally, Fura-2 Ca2+ imaging was performed on neurons dissociated from vagal sensory ganglia (n = 254 from 22 mice). The result showed that 63% of neurons responded to S1 protein. SARS-CoV-2 S1 protein can lead to direct activation of sensory C-fiber nerve terminals in the bronchopulmonary tract. Direct activation of C-fibers may contribute to coronavirus symptoms, and amplify viral spreading in a population.
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COVID-19 , SARS-CoV-2 , Animales , Ratones , Glicoproteína de la Espiga del Coronavirus/metabolismo , COVID-19/metabolismo , Nervio Vago/fisiología , Pulmón/fisiologíaRESUMEN
Locomotor recovery after spinal cord injury (SCI) remains an unmet challenge. Nerve transfer (NT), the connection of a functional/expendable peripheral nerve to a paralyzed nerve root, has long been clinically applied, aiming to restore motor control. However, outcomes have been inconsistent, suggesting that NT-induced neurological reinstatement may require activation of mechanisms beyond motor axon reinnervation (our hypothesis). We previously reported that to enhance rat locomotion following T13-L1 hemisection, T12-L3 NT must be performed within timeframes optimal for sensory nerve regrowth. Here, T12-L3 NT was performed for adult female rats with subacute (7-9 days) or chronic (8 weeks) mild (SCImi: 10 g × 12.5 mm) or moderate (SCImo: 10 g × 25 mm) T13-L1 thoracolumbar contusion. For chronic injuries, T11-12 implantation of adult hMSCs (1-week before NT), post-NT intramuscular delivery of FGF2, and environmentally enriched/enlarged (EEE) housing were provided. NT, not control procedures, qualitatively improved locomotion in both SCImi groups and animals with subacute SCImo. However, delayed NT did not produce neurological scale upgrading conversion for SCImo rats. Ablation of the T12 ventral/motor or dorsal/sensory root determined that the T12-L3 sensory input played a key role in hindlimb reanimation. Pharmacological, electrophysiological, and trans-synaptic tracing assays revealed that NT strengthened integrity of the propriospinal network, serotonergic neuromodulation, and the neuromuscular junction. Besides key outcomes of thoracolumbar contusion modeling, the data provides the first evidence that mixed NT-induced locomotor efficacy may rely pivotally on sensory rerouting and pro-repair neuroplasticity to reactivate neurocircuits/central pattern generators. The finding describes a novel neurobiology mechanism underlying NT, which can be targeted for development of innovative neurotization therapies.
Asunto(s)
Contusiones , Transferencia de Nervios , Traumatismos de la Médula Espinal , Ratas , Animales , Femenino , Traumatismos de la Médula Espinal/terapia , Axones , Plasticidad NeuronalRESUMEN
Sensory nerves belong to the afferent nerve part of the peripheral nervous system.Their role is to accept the stimuli inside and outside the body and transmit them to the center nerve system to form sensations or reflexes.Sensory nerve damage can be caused by trauma,tumor invasion,surgical injury,etc.Sensory nerve injury may cause decline or loss of some sensory organs function in patients.Damage of important sensory nerves such as optic nerves and auditory nerves can bring profound troubles to patients'lives.So far,the main clinical method to repair sensory nerves is autologous nerve transplantation.However,its application is limited by various factors,and the recovery effect of nerve function is often limited.Stem cells have the potential of multi-directional differentiation,which can differentiate into Schwann cells,and then secrete neurotrophic factors to promote axonal growth and myelin regeneration.Schwann cells directionally proliferate and form Bungner zones which guide nerve regeneration.Stem cells can also differentiate into neurons and construct nerve defect repair materials,which is an ideal choice for nerve repair.At present,the tissue engineering technology based on stem cells,combined with several key biotechnology,such as the use of biopolymerized or artificial surface micro-patterning nerve conduit to bridge nerve defects,and the use of microspheres to achieve the controlled release of extracellular matrix proteins and neurotrophic factors,is being widely studied and has achieved certain research results.This article reviews the research progress of stem cells in the repair of several major sensory nerves,such as optic nerves,olfactory nerves,cochlear nerves and sensory nerve fibers of sciatic nerve,expecting to provide a new perspective for neural repair of stem cells,broaden the preclinical research in nerve repair,and provide reference for follow-up clinical application.