Central Mechanisms I: Plasticity of Central Pathways

Abstract

Cough is the most common symptom for which individuals seek medical attention and spend health-care dollars. Despite the burden induced by cough, the current treatments for cough are only partially effective. Delineating the sites and mechanisms in the cough central network for changes in the cough reflex could lead to new therapeutic strategies and drug target sites for more effective treatments. The first synaptic target in the CNS for the cough-related sensory input is the second-order neurons in the nucleus tractus solitarius (NTS); these neurons reorganize the primary sensory information into a coherent output. The NTS neurons have been shown to undergo neuroplasticity under a variety of conditions, such as respiratory disorders, stress, and exposures to environmental pollutants. The NTS contains a rich innervation of substance P immunoreactive nerve terminals, suggesting that substance P might be important in altered cough reflex response. This chapter summarizes our current findings on the role of substance P in enhanced cough reflex as well as the potential NTS targets for the action of substance P.

Chronic ‘cough hypersensitivity syndrome’: A more precise label for chronic cough

“…Central nervous sensitization of the cough reflex has also been shown in animals including primates In particular, the role of substance P (SP) released from first-order neurones and acting on second-order neurones in the nucleus tractus solitarius (NTS) has been established, and the membrane receptor mechanisms on the second-order neurones has been analysed (45). With an upregulated cough reflex, due for example to inhaled pollutants, the SP levels in the NTS are increased, just as they are in the first-order neurones.…”

Postexercise Hypotension

“…Substance P in the NTS plays a major role as a neuromodulator, by interacting with other fast synaptic transmissions to regulate reflex function (6,16). Could exercise-induced substance P release reset blood pressure by shifting the synaptic excitability in the NTS through its interaction with GABAergic synaptic transmission?…”

“…Activation of the presynaptic substance P receptors results in a decrease in neurotransmitter release. The source and conditions under which substance P is released may determine the extent to which the presynaptic and postsynaptic mechanisms are integrated to shape neuronal NTS output (6). The increase in inhibitory transmission induced by substance P in the NTS during exercise (28) is consistent with its excitatory role on the soma/dendrites of the GABA interneurons.…”

Dilated intercellular spaces and chronic cough as an extra-oesophageal manifestation of gastrooesophageal reflux disease

“…These signals either centrally via the NTS or peripherally via the tracheobronchial tree are capable of sensitizing the airways for cough[20–24]; and key among the mediators of the central and peripheral sensitization for cough are the release of tachykinins, especially substance P[20–23]. …”