Opioid-induced ventilatory impairment (OIVI) remains a persistent and potentially life-threatening complication in the perioperative setting. Despite their efficacy in managing post-operative pain, opioids continue to pose a significant respiratory risk—one that contributes to avoidable morbidity, prolonged hospital stay, and, in severe cases, death. With over 14,000 estimated cases of OIVI annually in Australia alone, the burden is substantial.
This project investigates a novel neuropharmacological strategy to mitigate OIVI without compromising analgesia. It builds on the discovery that ventilatory suppression arises primarily from mu-opioid receptor activation in the pre-Bötzinger complex—distinct from the sites mediating analgesia.
We aim to leverage “crosstalk” between G-protein-coupled receptors by activating orexin-2 receptors in the brainstem to reverse opioid-induced respiratory depression. Central to this strategy is ALKS 2680, a selective orexin-2 receptor agonist currently in late-phase clinical development for narcolepsy. Through electrophysiological and behavioural studies in mice, we will evaluate its capacity to restore ventilatory drive in the presence of opioids.
If successful, this work will provide a mechanistic and translational foundation for clinical trials, potentially leading to safer postoperative opioid prescribing with reduced risk of OIVI.
A/Professor Paul Gray, Tess Cramond Pain and Research Centre, A/Professor Sebastian Furness, Dr Farhad Dehkhoda, The University of Queensland.
The project was awarded A$70,000 funding through the ANZCA research grants program for 2026.