NMDA and GABA receptors as potential targets in cough hypersensitivity syndrome

• Chronic cough is now regarded as part of a cough hypersensitivity syndrome.
• Afferent signals in brain nuclei may be amplified by neuropathic inflammation.
• N-methyl-d-aspartate and GABAB receptors may be targets for new antitussives.

Chronic cough is a common symptom that can be difficult to treat. It is proposed to be part of a cough hypersensitivity syndrome characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure. Upper airway and laryngeal neural dysfunction may also be present. There is evidence that this hypersensitivity may be due to sensory nerve damage caused by inflammatory, infective and allergic factors. Antitussive therapies based on opioid medications are generally not efficacious. Antagonists of N-methyl-d-aspartate receptors in the brain stem and use of GABAB receptor agonists such as baclofen acting centrally and possibly peripherally may represent novel therapeutic approaches.