Pulmonary pharmacology & therapeutics
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Both chronic cough and chronic pain are critical clinical issues in which a large number of patients remain unsatisfied with available treatments. These conditions have considerable effects on sufferers' quality of life, who often show co-morbidities such as anxiety and depression. There is therefore a pressing need to find new effective therapies. ⋯ There is a substantial literature around mechanisms of chronic pain which is likely to be useful in advancing knowledge about the pathologies of chronic cough. Here we compare the basic pain and cough pathways, in addition to the clinical features and possible pathophysiologies of each; including mechanisms of peripheral and central sensitisation which may underlie symptoms such as hyperalgesia and allodynia, and hypertussitvity and allotussivity. Due to the substantial overlap that emerges, it is likely that therapies may be effective over both areas.
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Cough suppression therapy (CST), also known as cough suppression physiotherapy and speech pathology management is a promising non-pharmacological therapeutic option for patients with refractory chronic cough. CST may consist of education, improving laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and counselling. It is an out-patient therapy delivered in 2-4 sessions. ⋯ The mechanism of action of CST is not clear, but it has been shown to reduce cough reflex sensitivity, paradoxical vocal fold movement (PVFM) and extrathoracic hyperresponsiveness. Further research is needed to determine the optimal components of CST, the characteristics of patients in whom it is most effective and to increase the understanding of its mechanisms of action. The effectiveness of CST in other respiratory conditions such as asthma, pulmonary fibrosis, chronic obstructive pulmonary disease and sarcoidosis should also be investigated.
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Pulm Pharmacol Ther · Oct 2013
Regulation of cough and action potentials by voltage-gated Na channels.
The classical role ascribed to voltage-gated Na channels is the conduction of action potentials. Some excitable tissues such as cardiac muscle and skeletal muscle predominantly express a single voltage-gated Na channels isoform. ⋯ Voltage-gated Na channel isoforms expressed in airway sensory neurons produce multiple distinct Na currents that underlie distinct aspects of sensory neuron function. The interaction between voltage-gated Na currents underlies the characteristic ability of airway sensory nerves to encode encounters with irritant stimuli into action potential discharge and evoke the cough reflex.
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A variety of foreign "invaders" such as viruses, bacteria and other particulates e.g., cigarette smoke, are inhaled, deposit on the airway surface and invade the "host." Mucins produced by the surface airway epithelium and by the submucosal glands are secreted into the airway lumen. Deposited particulates adhere to the mucus and are cleared via mucociliary transport and via cough. Mucins are major constituents of mucus, which is important in the clearance of inhaled materials. ⋯ Because there are so many small airways, their plugging is difficult to detect early, and this locus is known as a "silent zone." In chronic obstructive airway diseases, plugging of small airways may persist and increase over time, finally resulting in severe airway obstruction. Different obstructive airway diseases induce inflammatory signaling (including mucous hypersecretion) via different stimuli, but often via similar signaling pathways. Application of present knowledge of signaling that occurs with mucous hypersecretion can lead to novel therapies for hypersecretion and cough induced in conducting airways and could prevent plugging in small airways that can lead to clinical deterioration and death.
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The concept of placebo response has evolved in the past few years from the clinical trial setting and medical practice to a psychobiological model that gives us important information on how the patient's brain is modified by the psychosocial context around the therapy. In this review, some examples will be given where physiological or pathological conditions are altered following the administration of an inert substance along with verbal instructions tailored to induce expectation of a change, and explanations will be presented with details on neurotransmitter changes and neural pathways activated. Although nothing is known about the biological underpinnings of the placebo response in the respiratory system, this review may help extending the neurobiological investigation of placebos from conditions such as pain and Parkinson's disease to respiratory disorders and symptoms such as cough.