Birring Surinder S, Dicpinigaitis Peter V, Maher Toby M, Mazzone Stuart B, Page Clive P, Hawi Amale, Sciascia Thomas, Morice Alyn H
Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, King's College London, London, UK.
Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
Lung. 2025 May 13;203(1):62. doi: 10.1007/s00408-025-00812-8.
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.
慢性咳嗽对患者生活质量造成重大负担，并与不良健康后果相关。慢性咳嗽可能是外周和中枢神经系统变化导致神经超敏反应的结果，尽管其发病的确切机制尚未完全明确。阿片受体，特别是κ和μ受体，是慢性咳嗽治疗中的潜在靶点，因为它们在咳嗽行为涉及的外周和中枢神经通路中均起关键作用。吗啡作为一种μ阿片受体激动剂，是一种有效的咳嗽调节剂；然而，μ受体激动剂属于一类可导致呼吸抑制和欣快感的药物，具有很强的强化特性，可能导致过度使用和滥用。具有κ受体激动和μ受体拮抗双重作用机制的药物可能对慢性咳嗽的治疗有效且无滥用风险。本综述总结了目前对咳嗽超敏反应机制、κ和μ受体在咳嗽神经生理学中的作用以及将这些受体作为治疗慢性咳嗽新方法的临床潜力的认识。
