Central nervous system control of cough: pharmacological implications

Neural correlates coding stimulus level and perception of capsaicin-evoked urge-to-cough in humans

“…Relatively little is known about the higher brain circuitry that is activated when noxious stimuli are applied to the airways (Widdicombe et al, 2006;Mazzone et al, 2011b). We have previously mapped neural circuitry associated with noxious airway stimulation in humans by having participants inhale the TRPV1 agonist capsaicin while measuring regional changes in brain blood oxygen level-dependent (BOLD) responses using fMRI (Mazzone et al, 2007).…”

Cough-Anal Reflex May Be the Expression of a Pre-Programmed Postural Action

“…In support of such a proposal, Shima et al ( 1991 ) reported that in monkeys the stimulation of the posterior insular cortex is able to induce contractions in the contralateral muscles. Similarly, the mid-cingulate cortex has been reported to be active when voluntarily coughing, and also during a voluntary sniff or breath (Simonyan et al, 2007 ; Mazzone et al, 2011 ). Finally, it is noteworthy that cough-like actions may be elicited in the anesthetized cat by stimulating the amygdala or the suprasylvian gyrus with electrical pulses, and that the reflex-cough, triggered by stimulating the superior laryngeal nerves (afferent components), is inhibited if a simultaneous stimulus is applied to the orbital or cingulate gyri (Kito et al, 1977 ; Kasé et al, 1984 ).…”

“…Cough reflex, is aimed at protecting the respiratory tract from irritation agents, foreign bodies and microorganisms, either inhaled or in loco produced (Bolser and Davenport, 2002 ; Bessac and Jordt, 2010 ), such action escapes any voluntary control and its processing seems to be entirely based on brainstem structures (Baekey et al, 2001 ; Canning and Mori, 2010 ). Nevertheless, more and more literature reports that not only sensory and motor but also cognitive and affective mechanisms may play a role in controlling cough, being able either to promote or inhibit it (Widdicombe, 1995 ; Fong et al, 2004 ; Mazzone et al, 2007 , 2011 ; Davenport, 2009 ). Cough, like most respiratory maneuvers, can be also initiated at will, indeed cough or cough-like maneuvers are quite common in non-verbal communication, e.g., to require attention or express disagreement, to pretend to be ill or underline the symptoms of a real disease.…”

“…In the human being, urge-driven cough may be not exclusively governed by brainstem reflex circuitries, as other hierarchically higher brain areas, such as the insular, cingulate and somatosensory cortices, may provide an important contribution (Mazzone et al, 2011 ). Even if the exact role of these cortical areas is still unclear, it may be conceived that they take part in controlling the accessory muscles in cough, as well as in arranging the voluntary control of cough.…”

Sensations and regional brain responses evoked by tussive stimulation of the airways

“…by a drive to satiate the urge-to-cough, and that antagonism of the urge-to-cough could be a viable treatment strategy that would leave the critical cough reflex intact (Chung, 2011;Mazzone et al, 2011b;Morice, 2013;Morice et al, 2012). This review will discuss recent advances in the understanding of urge-to-cough that have been facilitated by heightened interest in the sensation.…”