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Article ; Online: Neural mechanisms of respiratory interoception.

Chan, Pei-Ying Sarah / Lee, Lu-Yuan / Davenport, Paul W

Autonomic neuroscience : basic & clinical

2024 Volume 253, Page(s) 103181

Abstract: Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. ...

Abstract	Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. Dyspnea can be differentiated into specific modalities. These respiratory sensory modalities lead to a general sensation of an Urge-to-Breathe, driven by a need to compensate for the modulation of ventilation that has occurred due to factors that have affected breathing. The multiafferent system for respiratory interoception can also lead to interpretation of the sensory signals resulting in respiratory related sensory experiences, including the Urge-to-Cough and Urge-to-Swallow. These behaviors are modalities that can be driven through the differentiation and integration of multiple afferent input into the respiratory neural comparator. Respiratory sensations require neural somatic and visceral interoceptive elements that include gated attention and detection leading to respiratory modality discrimination with subsequent cognitive decision and behavioral compensation. Studies of brain areas mediating cortical and subcortical respiratory sensory pathways are summarized and used to develop a model of an integrated respiratory neural network mediating respiratory interoception.
Language	English
Publishing date	2024-04-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2024.103181
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Article ; Online: TRP channels in airway sensory nerves.

Gu, Qihai / Lee, Lu-Yuan

Neuroscience letters

2021 Volume 748, Page(s) 135719

Abstract: Transient Receptor Potential (TRP) channels expressed in specific subsets of airway sensory nerves function as transducers and integrators of a diverse range of sensory inputs including chemical, mechanical and thermal signals. These TRP sensors can ... ...

Abstract	Transient Receptor Potential (TRP) channels expressed in specific subsets of airway sensory nerves function as transducers and integrators of a diverse range of sensory inputs including chemical, mechanical and thermal signals. These TRP sensors can detect inhaled irritants as well as endogenously released chemical substances. They play an important role in generating the afferent activity carried by these sensory nerves and regulating the centrally mediated pulmonary defense reflexes. Increasing evidence reported in recent investigations has revealed important involvements of several TRP channels (TRPA1, TRPV1, TRPV4 and TRPM8) in the manifestation of various symptoms and pathogenesis of certain acute and chronic airway diseases. This mini-review focuses primarily on these recent findings of the responses of these TRP sensors to the biological stresses emerging under the pathophysiological conditions of the lung and airways.
MeSH term(s)	Afferent Pathways/physiology ; Animals ; Humans ; Lung/innervation ; Lung/physiology ; Peripheral Nervous System ; Pulmonary Disease, Chronic Obstructive/genetics ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Sensory Receptor Cells/physiology ; Transient Receptor Potential Channels/physiology
Chemical Substances	Transient Receptor Potential Channels
Language	English
Publishing date	2021-02-12
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2021.135719
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Article ; Online: Inhibitory effect of sulfur dioxide inhalation on Hering-Breuer inflation reflex in mice: role of voltage-gated potassium channels.

Chan, Nai-Ju / Hsu, Chun-Chun / Lin, You Shuei / Lin, Ruei-Lung / Lee, Lu-Yuan

Journal of applied physiology (Bethesda, Md. : 1985)

2023 Volume 134, Issue 5, Page(s) 1075–1082

Abstract: Slowly adapting receptors (SARs), vagal mechanosensitive receptors located in the lung, play an important role in regulating the breathing pattern and Hering-Breuer inflation reflex (HBIR). Inhalation of high concentration of sulfur dioxide ( ... ...

Abstract	Slowly adapting receptors (SARs), vagal mechanosensitive receptors located in the lung, play an important role in regulating the breathing pattern and Hering-Breuer inflation reflex (HBIR). Inhalation of high concentration of sulfur dioxide (SO
MeSH term(s)	Rabbits ; Animals ; Mice ; Sulfur Dioxide/pharmacology ; Potassium Channels, Voltage-Gated/pharmacology ; Respiration ; Lung ; Reflex ; Vagus Nerve ; Apnea ; 4-Aminopyridine/pharmacology
Chemical Substances	Sulfur Dioxide (0UZA3422Q4) ; Potassium Channels, Voltage-Gated ; 4-Aminopyridine (BH3B64OKL9)
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00714.2022
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Article: Mechanisms Involved in the Stimulatory and Inhibitory Effects of 5-Hydroxytryptamine on Vagal Mechanosensitive Afferents in Rat Lung.

Lin, You Shuei / Hsu, Chun-Chun / Ruan, Ting / Lee, Lu-Yuan

Frontiers in physiology

2022 Volume 13, Page(s) 813096

Abstract: Mechanosensitive vagal afferents in the lung, rapidly and slowly adapting receptors (RARs and SARs, respectively), play an important role in eliciting the reflexes that regulate the normal airway function. A profound bronchoconstrictive effect of 5- ... ...

Abstract	Mechanosensitive vagal afferents in the lung, rapidly and slowly adapting receptors (RARs and SARs, respectively), play an important role in eliciting the reflexes that regulate the normal airway function. A profound bronchoconstrictive effect of 5-hydroxytryptamine (5-HT) has been extensively reported in various animal species, but its influence on the SAR and RAR activity is not known. This study investigated the effect of 5-HT on these receptors, and the possible mechanisms involved. Single-fiber activities of these afferents were measured in anesthetized, open-chest, and mechanically ventilated rats. Our results showed that intravenous injection of 5-HT evoked a consistent and pronounced stimulation of phasic RARs. In contrast, 5-HT generated an inconsistent and paradoxical action on SARs: no effect in 29% (5 of 17) of the SARs; stimulation in 35% (6 of 17); and inhibition in the remainder. These responses of both RARs and SARs to 5-HT were reproducible and dose-dependent. After the injection of a high dose of 5-HT (16 μg/kg), the receptor responses slowly reached a peak (after ∼8 s) and returned toward the baseline in ∼20 s, accompanied by a consistent increase in total pulmonary resistance and a decrease in dynamic lung compliance in a temporal pattern very similar to the increased receptor activity. When these changes in lung mechanics induced by 5-HT were prevented by pretreatment with salbutamol, a β
Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.813096
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Article: A Distinct Difference Between Air and Mucosal Temperatures in Human Respiratory Tract.

Khosravi, Mehdi / Lin, Ruei-Lung / Maskey, Ashish P / Pandey, Subodh / Lin, An-Hsuan / Lee, Lu-Yuan

Frontiers in medicine

2021 Volume 8, Page(s) 650637

Abstract: Extensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory ... ...

Abstract	Extensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory functions. However, the actual airway mucosal temperature and its dynamic changes during the respiratory cycle have not been directly measured. In previous studies, airway tissue temperature was often estimated by indirect measurement of the peak exhaled breath temperature (PEBT). In view of the poor thermal conductivity of air, we believe that the airway tissue temperature cannot be accurately determined by the exhaled air temperature, and this study aimed to test this hypothesis. We applied a miniature rapid-response temperature probe to measure directly the mucosal temperatures of trachea, major, lobar, and segmental bronchi in eight human subjects during a bronchoscopy procedure. Unlike the air temperature in the airway lumen, the mucosal temperature in these airway segments remained relatively stable and did not exhibit the phasic changes synchronous with respiratory cycles. The airway mucosal temperature increased progressively from the extra-thoracic trachea (35.7 ± 0.2°C) toward the segmental bronchus (36.9 ± 0.2°C). Most importantly, the temperatures measured directly at the mucosa of all these airway segments were substantially higher than the PEBT (31.7 ± 0.8°C). The recent findings of a close association between an increased PEBT and airway tissue inflammation have revealed the implication and potential of incorporating the PEBT measurement in the future clinical diagnosis of airway inflammation. Therefore, it is imperative to recognize this distinct difference in temperature between airway mucosa and exhaled air.
Language	English
Publishing date	2021-07-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.650637
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Article ; Online: Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C-fibres.

Lin, An-Hsuan / Hsu, Chun-Chun / Lin, You Shuei / Lin, Ruei-Lung / Lee, Lu-Yuan

The Journal of physiology

2020 Volume 598, Issue 5, Page(s) 1093–1108

Abstract: Key points: Brief inhalation of SO: Abstract: Inhalation of sulfur dioxide ( ... ...

Abstract	Key points: Brief inhalation of SO Abstract: Inhalation of sulfur dioxide (SO
MeSH term(s)	Animals ; Bronchi ; Lung ; Mice ; Nerve Fibers, Unmyelinated ; Rats ; Sulfur Dioxide/toxicity ; TRPV Cation Channels ; Vagus Nerve
Chemical Substances	TRPV Cation Channels ; Sulfur Dioxide (0UZA3422Q4)
Language	English
Publishing date	2020-02-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP279152
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Article ; Online: TRPA1 ion channels: a gateway to airway irritation and reflex responses induced by inhaled oxidants.

Lee, Lu-Yuan

The Journal of physiology

2010 Volume 588, Issue Pt 5, Page(s) 747–748

MeSH term(s)	Administration, Inhalation ; Air Pollutants/adverse effects ; Animals ; Calcium Channels/metabolism ; Humans ; Lung/drug effects ; Lung/innervation ; Lung/physiopathology ; Models, Biological ; Nerve Tissue Proteins/metabolism ; Oxidants/administration & dosage ; Oxidants/adverse effects ; Pneumonia/chemically induced ; Pneumonia/physiopathology ; Reflex, Abnormal/drug effects ; TRPA1 Cation Channel ; Transient Receptor Potential Channels/metabolism
Chemical Substances	Air Pollutants ; Calcium Channels ; Nerve Tissue Proteins ; Oxidants ; TRPA1 Cation Channel ; TRPA1 protein, human ; Transient Receptor Potential Channels
Language	English
Publishing date	2010-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2010.187286
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Article ; Online: Cough responses to inhaled irritants are enhanced by eosinophil major basic protein in awake mice.

Lin, An-Hsuan / Athukorala, Ashami / Gleich, Gerald J / Lee, Lu-Yuan

American journal of physiology. Regulatory, integrative and comparative physiology

2019 Volume 317, Issue 1, Page(s) R93–R97

Abstract: A distinct association between airway eosinophilia and chronic cough is well documented. Eosinophil granule-derived cationic proteins, such as major basic protein (MBP), have been shown to activate and enhance the excitability of bronchopulmonary C-fiber ...

Abstract	A distinct association between airway eosinophilia and chronic cough is well documented. Eosinophil granule-derived cationic proteins, such as major basic protein (MBP), have been shown to activate and enhance the excitability of bronchopulmonary C-fiber sensory nerves, which may then lead to an increase in cough sensitivity. This study was carried out to determine whether cough responses to inhaled irritant gases were altered by delivery of MBP into the airways. An awake mouse moved freely in a recording chamber that was ventilated with a constant flow of air or irritant gas mixture. Cough responses to separate inhalation challenges of sulfur dioxide (SO
MeSH term(s)	Administration, Inhalation ; Ammonia/administration & dosage ; Ammonia/toxicity ; Animals ; Cough/chemically induced ; Eosinophil Major Basic Protein/pharmacology ; Irritants/administration & dosage ; Irritants/toxicity ; Mice ; Respiratory Physiological Phenomena ; Sulfur Dioxide/administration & dosage ; Sulfur Dioxide/toxicity ; Wakefulness
Chemical Substances	Irritants ; Sulfur Dioxide (0UZA3422Q4) ; Ammonia (7664-41-7) ; Eosinophil Major Basic Protein (EC 3.1.27.-)
Language	English
Publishing date	2019-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00081.2019
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Article: Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT

Hsu, Chun-Chun / Ruan, Ting / Lee, Lu-Yuan / Lin, You Shuei

Frontiers in physiology

2019 Volume 10, Page(s) 642

Abstract: 5-hydroxytryptamine (5-HT) is an inflammatory mediator known to be released in lung. Capsaicin-sensitive lung vagal (CSLV) afferents function as a primary sensor for detecting chemical stimuli and produce consequent reflexes during lung inflammation. To ... ...

Abstract	5-hydroxytryptamine (5-HT) is an inflammatory mediator known to be released in lung. Capsaicin-sensitive lung vagal (CSLV) afferents function as a primary sensor for detecting chemical stimuli and produce consequent reflexes during lung inflammation. To characterize the effect of 5-HT on CSLV afferents, responses of cardiorespiratory reflexes and single-unit C-fiber afferents to right-atrial injections of 5-HT were investigated in anesthetized Sprague-Dawley rats. Bolus injection of 5-HT (8 μg/kg) caused an immediate augmented breath and apnea, accompanied by hypotension and bradycardia. These initial responses were then followed by a brief pressor response and a more sustained depressor response. After a perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 5-HT still triggered the augmented breath, but no longer evoked the apnea, bradycardia and hypotension, indicating an involvement of C-fiber activation. The remaining augmented breath induced by 5-HT after perineural capsaicin treatment was totally eliminated by vagotomy. To further study the effect of 5-HT on CSLV afferents, activities arising from these afferents were determined using the single-fiber recording technique. Right-atrial injection of 5-HT evoked an intense discharge in CSLV afferents in a dose-dependent manner. The highest dose of 5-HT (16 μg/kg) activated 79% (19/24) of CSLV afferents which were also sensitive to capsaicin (0.8 μg/kg). The pretreatment of tropisetron, a selective antagonist of the 5-HT
Language	English
Publishing date	2019-05-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2019.00642
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Article ; Online: Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons.

Hsu, Chun-Chun / Lee, Lu-Yuan

Journal of applied physiology (Bethesda, Md. : 1985)

2015 Volume 118, Issue 12, Page(s) 1533–1543

Abstract: Both transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are abundantly expressed in bronchopulmonary C-fiber sensory nerves and can be activated by a number of endogenous inflammatory mediators. A recent study has reported a ...

Abstract	Both transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are abundantly expressed in bronchopulmonary C-fiber sensory nerves and can be activated by a number of endogenous inflammatory mediators. A recent study has reported a synergistic effect of simultaneous TRPA1 and TRPV1 activations in vagal pulmonary C-fiber afferents in anesthetized rats, but its underlying mechanism was not known. This study aimed to characterize a possible interaction between these two TRP channels and to investigate the potential role of Ca(2+) as a mediator of this interaction in isolated rat vagal pulmonary sensory neurons. Using the perforated patch-clamp recording technique, our study demonstrated a distinct positive interaction occurring abruptly between TRPA1 and TRPV1 when they were activated simultaneously by their respective agonists, capsaicin (Cap) and allyl isothiocyanate (AITC), at near-threshold concentrations in these neurons. AITC at this low concentration evoked only minimal or undetectable responses, but it markedly amplified the Cap-evoked current in the same neurons. This potentiating effect was eliminated when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, when Ca(2+) was removed from the extracellular solution, the synergistic effect of Cap and AITC on pulmonary sensory neurons was completely abrogated, clearly indicating a critical role of Ca(2+) in mediating the action. These results suggest that this TRPA1-TRPV1 interaction may play a part in regulating the sensitivity of pulmonary sensory neurons during airway inflammatory reaction.
MeSH term(s)	Animals ; Bronchi/innervation ; Calcium/physiology ; Calcium Channel Agonists/pharmacology ; Capsaicin/pharmacology ; Drug Synergism ; Ions ; Lung/innervation ; Male ; Nerve Fibers, Unmyelinated/physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Sensory Receptor Cells/physiology ; TRPA1 Cation Channel ; TRPC Cation Channels/drug effects ; TRPC Cation Channels/metabolism ; TRPC Cation Channels/physiology ; TRPV Cation Channels/drug effects ; TRPV Cation Channels/metabolism ; TRPV Cation Channels/physiology
Chemical Substances	Calcium Channel Agonists ; Ions ; TRPA1 Cation Channel ; TRPC Cation Channels ; TRPV Cation Channels ; Trpa1 protein, rat ; Trpv1 protein, rat ; Capsaicin (S07O44R1ZM) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2015-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00043.2015
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