Most cited article - PubMed ID 28937249
Vagotomy decreases the neuronal activities of medulla oblongata and alleviates neurogenic inflammation of airways induced by repeated intra-esophageal instillation of HCl in guinea pigs
Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.
- MeSH
- Chronic Disease MeSH
- Capsaicin adverse effects MeSH
- Cough chemically induced physiopathology MeSH
- TRPV Cation Channels agonists physiology MeSH
- TRPA1 Cation Channel agonists physiology MeSH
- Humans MeSH
- Sensory Receptor Cells drug effects physiology MeSH
- Vagus Nerve drug effects physiopathology MeSH
- Nasal Mucosa drug effects physiopathology MeSH
- Syndrome MeSH
- Trachea drug effects physiopathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Capsaicin MeSH
- TRPV Cation Channels MeSH
- TRPA1 Cation Channel MeSH
- TRPA1 protein, human MeSH Browser
- TRPV1 protein, human MeSH Browser
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.
- MeSH
- Action Potentials drug effects physiology MeSH
- Antitussive Agents pharmacology therapeutic use MeSH
- Voltage-Gated Sodium Channel Blockers pharmacology therapeutic use MeSH
- Cough drug therapy physiopathology MeSH
- Humans MeSH
- Nociceptors drug effects metabolism MeSH
- Voltage-Gated Sodium Channels physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Antitussive Agents MeSH
- Voltage-Gated Sodium Channel Blockers MeSH
- Voltage-Gated Sodium Channels MeSH
Laboratory research of cough reflex utilizes almost exclusively male guinea pigs - a practice that represents a significant obstacle in the successful translation of results into clinical practice. Chronic hypersensitivity cough syndrome affects mostly postmenopausal women and it represents significant decrease in patient's quality of life. No cause for such exaggerated cough can be found, therefore this condition cannot be treated appropriately. One of the reasons leading to the lack of relevant data about mechanisms responsible for hypersensitivity of cough related pathways is nowadays widely discussed gender bias, which is present in nearly all branches of biomedical research. Since gender differences in cough reflex physiology do exist in humans, it would be reasonable to study cough-related phenomena on both sexes of laboratory animals. In this study, we focused on detailed characterization of cough response of female guinea pigs to aerosols of commonly used tussive agents (capsaicin, distilled water, allyl isothiocyanate, cinnamaldehyde, citric acid). In pooled data from multiple challenges we found no statistical difference in number of cough and cough latency between sexes. Based on our results we conclude that the utilization of female guinea pigs model does not lead to messy data and can be used in basic cough research.
- MeSH
- Acrolein analogs & derivatives toxicity MeSH
- Capsaicin toxicity MeSH
- Cough chemically induced physiopathology MeSH
- Citric Acid toxicity MeSH
- Disease Models, Animal * MeSH
- Guinea Pigs MeSH
- Sex Characteristics * MeSH
- Animals MeSH
- Check Tag
- Guinea Pigs MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acrolein MeSH
- cinnamaldehyde MeSH Browser
- Capsaicin MeSH
- Citric Acid MeSH
Respiratory sinus arrhythmia (RSA), i.e. heart rate (HR) variations during inspiration and expiration, is considered as a noninvasive index of cardiac vagal control. Mitral valve prolapse (MVP) could be associated with increased cardiovascular risk; however, the studies are rare particularly at adolescent age. Therefore, we aimed to study cardiac vagal control indexed by RSA in adolescent patients suffering from MVP using short-term heart rate variability (HRV) analysis. We examined 12 adolescents (girls) with MVP (age 15.9±0.5 years) and 12 age and gender matched controls. Resting ECG was continuously recorded during 5 minutes. Evaluated HRV indices were RR interval (ms), rMSSD (ms), pNN50 (%), log HF (ms(2)), peak HF (Hz) and respiratory rate (breaths/min). RR interval was significantly shortened in MVP group compared to controls (p=0.004). HRV parameters-rMSSD, pNN50 and log HF were significantly lower in MVP compared to controls (p=0.017, p=0.014, p= 0.015 respectively). Our study revealed reduced RSA magnitude indicating impaired cardiac vagal control in MVP already at adolescent age that could be crucial for early diagnosis of cardiovascular risk in MVP.
- MeSH
- Electrocardiography methods MeSH
- Body Mass Index * MeSH
- Humans MeSH
- Adolescent MeSH
- Vagus Nerve physiology MeSH
- Mitral Valve Prolapse diagnosis physiopathology MeSH
- Respiratory Sinus Arrhythmia physiology MeSH
- Heart Rate physiology MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The sinonasal mucosa has an essential role in defense mechanisms of the upper respiratory tract. The innate immune system presents the primary defense against noxious microorganisms followed by induction of the adaptive immune mechanisms as a consequence of the presence of pathogens. This well-known activation of adaptive immune system in response to presence of the antigen on mucosal surfaces is now broadly applicated in vaccinology research. Prevention of infectious diseases belongs to substantial challenges in maintaining the population health. Non-invasive, easily applicable mucosal vaccination purposes various research opportunities that could be usable in daily practice. However, the existence of multiple limitations such as rapid clearance of vaccine from nasal mucosa by means of mucociliary transport represents a great challenge in development of safe and efficient vaccines. Here we give an updated view on nasal functions with focus on nasal mucosal immunity and its potential application in vaccination in nearly future.
- MeSH
- Administration, Intranasal MeSH
- Humans MeSH
- Nasal Mucosa drug effects physiology MeSH
- Respiratory Mucosa drug effects physiology MeSH
- Laryngeal Mucosa drug effects physiology MeSH
- Immunity, Mucosal drug effects physiology MeSH
- Trachea drug effects physiology MeSH
- Vaccines administration & dosage MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Vaccines MeSH