Airway Sensory Nerve Plasticity in Asthma and Chronic Cough

Airway sensory nerves detect a wide variety of chemical and mechanical stimuli, and relay signals to circuits within the brainstem that regulate breathing, cough, and bronchoconstriction. Recent advances in histological methods, single cell PCR analysis and transgenic mouse models have illuminated a remarkable degree of sensory nerve heterogeneity and have enabled an unprecedented ability to test the functional role of specific neuronal populations in healthy and diseased lungs. This review focuses on how neuronal plasticity contributes to development of two of the most common airway diseases, asthma and chronic cough, and discusses the therapeutic implications of emerging treatments that target airway sensory nerves.

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Airway Neuropeptides: Roles in Fine Tuning and In Disease?

Physiology ◽

10.1152/physiologyonline.1989.4.3.116 ◽

1989 ◽

Vol 4 (3) ◽

pp. 116-120

Author(s):

PJ Barnes

Keyword(s):

Blood Flow ◽

Sensory Nerves ◽

Fine Tuning ◽

Therapeutic Implications ◽

Airway Diseases ◽

Airway Caliber

Many neuropeptides have recently been identified in airways, with potent effects on airway caliber, blood flow, and secretions, raising the possibility that they are involved in airway diseases, such as asthma. Neuropeptides in sensory nerves induce inflammatory effects and may also contribute to the pathology of asthma. These findings may have important therapeutic implications.

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Molecular Diversity of the Syndinean Genus Euduboscquella Based on Single-Cell PCR Analysis

Applied and Environmental Microbiology ◽

10.1128/aem.06678-11 ◽

2011 ◽

Vol 78 (2) ◽

pp. 334-345 ◽

Cited By ~ 29

Author(s):

Tsvetan R. Bachvaroff ◽

Sunju Kim ◽

Laure Guillou ◽

Charles F. Delwiche ◽

D. Wayne Coats

Keyword(s):

Large Subunit ◽

Small Subunit ◽

Base Change ◽

Pcr Analysis ◽

Ssu Rrna ◽

Compensatory Base Change ◽

Content Type ◽

Single Cell Pcr ◽

Group I ◽

Lsu Rrna

ABSTRACTThe genusEuduboscquellais one of a few described genera within the syndinean dinoflagellates, an enigmatic lineage with abundant diversity in marine environmental clone libraries based on small subunit (SSU) rRNA. The region composed of the SSU through to the partial large subunit (LSU) rRNA was determined from 40 individual tintinnid ciliate loricae infected withEuduboscquellasampled from eight surface water sites in the Northern Hemisphere, producing seven distinct SSU sequences. The corresponding host SSU rRNA region was also amplified from eight host species. The SSU tree ofEuduboscquellaand syndinean group I sequences from environmental clones had seven well-supported clades and one poorly supported clade across data sets from 57 to 692 total sequences. The genusEuduboscquellaconsistently formed a supported monophyletic clade within a single subclade of group I sequences. For most parasites with identical SSU sequences, the more variable internal transcribed spacer (ITS) to LSU rRNA regions were polymorphic at 3 to 10 sites. However, inE. cachonithere was variation between ITS to LSU copies at up to 20 sites within an individual, while in a parasite ofTintinnopsisspp., variation between different individuals ranged up to 19 polymorphic sites. However, applying the compensatory base change model to the ITS2 sequences suggested no compensatory changes within or between individuals with the same SSU sequence, while one to four compensatory changes between individuals with similar but not identical SSU sequences were found. Comparisons between host and parasite phylogenies do not suggest a simple pattern of host or parasite specificity.

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Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Hypertension ◽

10.1161/hyp.78.suppl_1.mp45 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Sean D Stocker ◽

Leon J DeLalio

Keyword(s):

Heart Rate ◽

Renovascular Hypertension ◽

Sensory Nerve ◽

Experimental Models ◽

Sensory Nerves ◽

Male Rats ◽

Wild Type ◽

Renal Nerve ◽

Trpv1 Channels ◽

Arterial Blood

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

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Very Early Neurophysiological Study in Guillain-Barre Syndrome

European Neurology ◽

10.1159/000494261 ◽

2018 ◽

Vol 80 (1-2) ◽

pp. 100-105 ◽

Cited By ~ 1

Author(s):

Jiaoting Jin ◽

Fangfang Hu ◽

Xing Qin ◽

Xuan Liu ◽

Min Li ◽

...

Keyword(s):

Nerve Conduction ◽

Nerve Conduction Velocity ◽

Tibial Nerve ◽

Early Stage ◽

Motor Nerve ◽

Sensory Nerve ◽

Sensory Nerves ◽

Motor Nerve Conduction ◽

Abnormal Rate ◽

Motor Nerves

Purpose: The diagnosis of Guillain-Barre syndrome (GBS) in the very early stage may be challenging. Our aim was to report the neurophysiological abnormalities in GBS within 4 days of clinical onset. We expected that GBS will be diagnosed by the assistance of neurophysiological study in the very early stage. Methods: We prospectively recruited patients with a diagnosis of GBS discharged from First Affiliated Hospital of Xi’an Jiaotong University and Xi Jing Hospital. Patients were classified into 3 groups according to the onset of symptoms to electromyography examination interval (OEI). The neurophysiological findings were carried out using standard procedures. All patients were examined by the same experienced neurophysiologist. Results: There were not significant group differences in abnormal rate, distal motor latency (DML), motor nerve conduction velocity (MNCV), F response (FR), compound muscle action potential (CMAP), conduction block (CB), sensory nerve action potential (SNAP), and sensory nerve conduction velocity among OEI ≤4 days, 4< OEI ≤10 days, and OEI > 10 days groups. Motor nerves were more affected than sensory nerves in neurophysiological presentation in very early stage patients. The difference of motor nerves and sensory nerves was statistically significant in lower limbs, but was not in upper limbs. In motor nerve conduction studies, the abnormal rate of DML, MNCV, FR, CB was more common seen in ulnar and peroneal nerve than median and tibial nerve, the abnormal rate of CMAP was the same in ulnar, median, peroneal and tibial nerve. In sensory nerve conduction studies, the abnormal rate of ulnar nerve and median nerve was higher than the superficial peroneal nerve and sural nerve. The OEI was not correlated with the SNAP decrease rate of median (r = 0.10, p = 0.23) and ulnar (r = 0.26, p = 0.06) but was statistically correlated with sural SNAP decrease rate (r = 0.29, p = 0.04). The sural-sparing pattern phenomenon was the most commonly discovered phenomenon in very early stage patients (OEI ≤4 days), followed by patients with 4< OEI ≤10 days, ultimately found in patients with OEI > 10 days. Conclusions: We suggest performing neurophysiological examination as soon as possible for suspected GBS patients, particularly focusing on multi-spots inspection of ulnar and peroneal nerves, and paying close attention to sural-sparing patterns.

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Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): from clinical diagnosis towards genetic testing

Medizinische Genetik ◽

10.1515/medgen-2021-2098 ◽

2021 ◽

Vol 33 (4) ◽

pp. 301-310

Author(s):

Andreas Thieme ◽

Christel Depienne ◽

Dagmar Timmann

Keyword(s):

Cerebellar Ataxia ◽

Chronic Cough ◽

Late Onset ◽

Neurological Diseases ◽

Brain Mri ◽

Genetic Research ◽

Sensory Nerve ◽

Repeat Expansions ◽

Factor C ◽

Pentanucleotide Repeat

Abstract The cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset and recessively inherited ataxia. For many years, CANVAS has been diagnosed based on the clinical phenotype. Only recently, a large biallelic pentanucleotide repeat expansion in the replication factor C subunit 1 (RFC1) gene has been identified as the underlying genetic cause for the large majority of CANVAS cases. Subsequently, other phenotypes such as ataxia with chronic cough, incomplete CANVAS and MSA-C-like phenotypes have been associated with biallelic RFC1 repeat expansions. Because of this heterogeneity it has been suggested to change the name of the disease to “RFC1 disease”. Chronic cough is characteristic and can precede neurological symptoms by years or decades. In the neurological examination signs of cerebellar, sensory, and vestibular ataxia are frequently observed. Nerve conduction studies usually show absent or markedly reduced sensory nerve action potentials. On brain MRI cerebellar degeneration and spinal cord alterations are common. In later disease stages more widespread neurodegeneration with additional involvement of the brainstem and basal ganglia is possible. As yet, the exact incidence of RFC1-associated neurological diseases remains uncertain although first studies suggest that RFC1-related ataxia is common. Moreover, the pathophysiological mechanisms caused by the large biallelic pentanucleotide repeat expansions in RFC1 remain elusive. Future molecular and genetic research as well as natural history studies are highly desirable to pave the way towards personalized treatment approaches.

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Approach to the Patient with Cough

10.2310/fm.1478 ◽

2018 ◽

Author(s):

Christopher H. Fanta

Keyword(s):

Respiratory Tract ◽

Chronic Cough ◽

Lower Respiratory Tract ◽

Airflow Obstruction ◽

Sensory Nerve ◽

Lung Parenchyma ◽

Flow Volume ◽

Respiratory Compromise ◽

Cough Reflex ◽

Persistent Cough

The cough reflex is critically important in the clearance of abnormal airway secretions and protection of the lower respiratory tract from aspirated foreign matter. A weak or ineffective cough can lead to respiratory compromise from even a relatively minor bronchial infection. Persistent cough is often one of a constellation of symptoms indicative of respiratory disease—a potential clue in the differential diagnosis of the patient’s illness. Given the widespread distribution of sensory nerve endings of the cough reflex throughout the upper and lower respiratory tract, it is not surprising that myriad respiratory diseases, involving lung parenchyma and airways, can manifest with cough. Sometimes cough is the sole or predominant symptom in a patient who is otherwise well. Evaluating and treating the patient with persistent cough who has few, if any, other respiratory symptoms is a common challenge for the practicing physician. This review covers the normal cough mechanism, impaired cough, pathologic cough, cough suppressant therapy, and new developments. Figures show a flow-volume loop during cough, a posteroanterior chest x-ray in a patient presenting with chronic cough, flow-volume curves and spirograms documenting expiratory airflow obstruction, and the approach to the patient with chronic cough. The table lists selected examples of extrapulmonary physical findings of potential importance in the assessment of cough. This review contains 4 highly rendered figures, 1 table, and 94 references.

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TrkA inhibitor promotes motor functional regeneration of recurrent laryngeal nerve by suppression of sensory nerve regeneration

Scientific Reports ◽

10.1038/s41598-020-72288-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hiroshi Suzuki ◽

Koji Araki ◽

Toshiyasu Matsui ◽

Yuya Tanaka ◽

Kosuke Uno ◽

...

Keyword(s):

Recurrent Laryngeal Nerve ◽

Nerve Regeneration ◽

Vocal Fold ◽

Compound Muscle Action Potential ◽

Motor Nerve ◽

Sensory Nerve ◽

Laryngeal Nerve ◽

Sensory Nerves ◽

Nucleus Ambiguus ◽

Functional Regeneration

Abstract Recurrent laryngeal nerve (RLN) injury, in which hoarseness and dysphagia arise as a result of impaired vocal fold movement, is a serious complication. Misdirected regeneration is an issue for functional regeneration. In this study, we demonstrated the effect of TrkA inhibitors, which blocks the NGF-TrkA pathway that acts on the sensory/automatic nerves thus preventing misdirected regeneration among motor and sensory nerves, and thereby promoting the regeneration of motor neurons to achieve functional recovery. RLN axotomy rat models were used in this study, in which cut ends of the nerve were bridged with polyglycolic acid-collagen tube with and without TrkA inhibitor (TrkAi) infiltration. Our study revealed significant improvement in motor nerve fiber regeneration and function, in assessment of vocal fold movement, myelinated nerve regeneration, compound muscle action potential, and prevention of laryngeal muscle atrophy. Retrograde labeling demonstrated fewer labeled neurons in the vagus ganglion, which confirmed reduced misdirected regeneration among motor and sensory fibers, and a change in distribution of the labeled neurons in the nucleus ambiguus. Our study demonstrated that TrkAi have a strong potential for clinical application in the treatment of RLN injury.

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Neuropeptides and nasal secretion

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1991.261.4.l223 ◽

1991 ◽

Vol 261 (4) ◽

pp. L223-L235 ◽

Cited By ~ 7

Author(s):

J. N. Baraniuk ◽

M. Kaliner

Keyword(s):

Nasal Mucosa ◽

Defense Mechanism ◽

Sensory System ◽

Sensory Nerve ◽

Sympathetic Nerves ◽

Mucosal Injury ◽

Sensory Nerves ◽

Neurokinin A ◽

Sympathetic Nervous Systems ◽

Glandular Secretion

The nasal mucosa is innervated by the sensory, parasympathetic, and sympathetic nervous systems. Nociceptive sensory nerves are stimulated by mucosal injury, inhalation of irritants, or mast cell degranulation and release of the calcitonin gene-related peptide, the tachykinins substance P and neurokinin A, and other peptides by the axon response mechanism. Sensory nerve stimulation initiates systemic reflexes, such as the sneeze, and central parasympathetic reflexes which release acetylcholine, vasoactive intestinal peptide, and other peptides and lead to glandular secretion. In concert, these proinflammatory neural responses lead to vasodilation, vascular permeability, and glandular secretion. Sympathetic nerves release neuropeptide Y and norepinephrine, potent vasoconstrictors which act to decompress the nasal mucosa and produce nasal patency. The balance between the effects of parasympathetic and sympathetic neurotransmitters may regulate nasal homeostasis, whereas the nociceptive sensory system may be held in reserve as a defense mechanism. Dysfunction of these systems may lead to pathological nasal syndromes. In the future, specific neuropeptide agonists and antagonists may be useful for the treatment of human rhinitic diseases.

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