Cough reflex hypersensitivity: A role for neurotrophins

ABSTRACT

Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

KEYWORDS:

• cough
• hypersensitivity
• nerve growth factor
• nerves
• CNS
• airways
• mechanisms

Acknowledgments

The authors are thankful to the late Dr. Dom Spina (King's College London), Prof. Sam Kombian, and Prof. Yunus Luqmani (University of Kuwait) for their constructive comments during the preparation of this article. We also appreciate the assistance Ms. Rhema Babyson for her excellent work in preparing the figures.

Declaration of interest

The authors report no conflicts of interest.