Kappa and Mu Opioid Receptors in Chronic Cough: Current Evidence and Future Treatment

Chronic cough is a significant burden on patient quality of life and is associated with poor health outcomes. Chronic cough may be a result of neural hypersensitivity due to changes in both the peripheral and the central nervous systems, although the exact mechanisms underlying its pathogenesis are not completely understood. Opioid receptors, specifically kappa and mu, are potential therapeutic targets in the management of chronic cough because they play a pivotal role in both the peripheral and the central neural pathways implicated in the act of coughing. Morphine, a mu opioid receptor agonist, is an effective cough modulator; however, mu receptor agonists are part of a drug class that can induce respiratory depression and euphoria, with strong reinforcing properties that may lead to excessive use and abuse. Drugs with a dual-acting mechanism of kappa receptor agonism and mu receptor antagonism may be effective in the management of chronic cough without the potential for abuse. This review summarizes the current understanding of the mechanisms of cough hypersensitivity, the role of the kappa and mu receptors in the neurophysiology of cough, and the clinical potential of targeting these receptors as a novel way of managing chronic cough.