Peripheral neural circuitry in cough

Taylor‐Clark, Thomas E.

doi:10.1016/j.coph.2015.02.001

Cited by 13 publications

(8 citation statements)

References 124 publications

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“…The vast majority of vagal airway afferents are unmyelinated C fibers that innervate the epithelial layer [10, 13, 24, 25]. These nerves are sensitive to a wide-range of noxious stimuli (e.g.…”

Section: Sensory Afferent Nerves Involved In Coughmentioning

confidence: 99%

“…These changes in ion channel and neuropeptide expression are hypothesized to induce long lasting changes in the function of airway afferents associated with cough [10, 145]. A direct role of ROS in chronic plasticity has not been studied.…”

Section: Potential Role Of Ros In Chronic Plasticitymentioning

confidence: 99%

“…Recent evidence suggests that oxidative stress can evoke profound effects on airway afferent nerves, particularly through the modulation of neuronal transient receptor potential (TRP) channels. Although mammals share similarities in their respiratory physiology and airway afferent pharmacology, the cough reflex is only reliably present in guinea pigs and larger mammals [8–10]. Rats and mice do not possess a recognizable cough reflex, although these mammals have proved useful in elucidating aspects of airway afferent neurophysiology.…”

Section: Introductionmentioning

confidence: 99%

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Role of reactive oxygen species and TRP channels in the cough reflex

Taylor‐Clark

2016

Cell Calcium

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The cough reflex is evoked by noxious stimuli in the airways. Although this reflex is essential for health, it can be triggered chronically in inflammatory and infectious airway disease. Neuronal transient receptor potential (TRP) channels such as ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are polymodal receptors expressed on airway nociceptive afferent nerves. Reactive oxygen species (ROS) and other reactive compounds are associated with inflammation, from either NADPH oxidase or mitochondria. These reactive compounds cause activation and hyperexcitability of nociceptive afferents innervating the airways, and evidence suggests key contributions of TRPA1 and TRPV1.

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Section: Sensory Afferent Nerves Involved In Coughmentioning

confidence: 99%

Section: Potential Role Of Ros In Chronic Plasticitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of reactive oxygen species and TRP channels in the cough reflex

Taylor‐Clark

2016

Cell Calcium

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“…The vagus is a mixed nerve containing afferents that consist of fast conducting myelinated A fibers, slow conducting unmyelinated C fibers, and parasympathetic cholinergic efferent fibers. Stimulation of vagal sensory fibers has been shown to regulate rate and depth of breathing, basal tidal volume via the Herring-Breuer reflex (Carr and Undem 2003) (Paintal 1973) (Widdicombe and Lee 2001), cough (Canning and Chou 2009;Taylor-Clark 2015), and innervation of neuroepithelial bodies (Chang et al 2015). The bradycardia observed in response to lung inflation (Shepherd 1981) and to inhalation of noxious stimuli (Hazari et al 2011;Hooper et al 2016) is thought to be mediated by afferents of vagal origin.…”

Section: Introductionmentioning

confidence: 99%

Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats

et al. 2018

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The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1‐sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague‐Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1‐expressing afferent soma at the level of T1–T4 dorsal root ganglia pleura. This treatment abolished all sympatho‐excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9–10 weeks post‐RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli.

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“…The nodose neurons have their central terminations well-defined in the nucleus of the solitary tract (nTS), whereas jugular neurons have been recently shown to terminate in the paratrigeminal nucleus (Pa5). These sensory nuclei relay signal to the respiratory central pattern generator within the brainstem, which is responsible for reflex coughing, as well as to higher brain structures for the perception of airway irritation, which are needed for behavioral modulation of coughing (Canning et al 2006, Taylor-Clark 2015, Mazzone and Undem 2016.…”

Section: Airway Sensory Nerves and Coughmentioning

confidence: 99%

The Prospect for Potent Sodium Voltage-Gated Channel Blockers to Relieve an Excessive Cough

Brozmanová

Pavelková²

2020

Physiol Res

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An excessive, irritable, productive or non-productive coughing associated with airway inflammation belongs to pathological cough. Increased activation of airway vagal nociceptors in pathological conditions results from dysregulation of the neural pathway that controls cough. A variety of mediators associated with airway inflammation overstimulate these vagal airway fibers including C-fibers leading to hypersensitivity and hyperreactivity. Because current antitussives have limited efficacy and unwanted side effects there is a continual demand for the development of a novel more effective antitussives for a new efficacious and safe cough treatment. Therefore, inhibiting the activity of these vagal C-fibers represents a rational approach to the development of effective antitussive drugs. This may be achieved by blocking inflammatory mediator receptors or by blocking the generator potential associated with the specific ion channels. Because voltage-gated sodium channels (NaVs) are absolutely required for action potentials initiation and conduction irrespective of the stimulus, NaVs become a promising neural target. There is evidence that NaV1.7, 1.8 and 1.9 subtypes are predominantly expressed in airway cough-triggering nerves. The advantage of blocking these NaVs is suppressing C-fiber irrespective to stimuli, but the disadvantage is that by suppressing the nerves is may also block beneficial sensations and neuronal reflex behavior. The concept is that new antitussive drugs would have the benefit of targeting peripheral airway nociceptors without inhibiting the protective cough reflex.

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Peripheral neural circuitry in cough

Cited by 13 publications

References 124 publications

Role of reactive oxygen species and TRP channels in the cough reflex

Role of reactive oxygen species and TRP channels in the cough reflex

Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats

The Prospect for Potent Sodium Voltage-Gated Channel Blockers to Relieve an Excessive Cough

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