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Opioids depress cortical centers responsible for the volitional control of respiration
journal contribution
posted on 2023-06-07, 16:03 authored by Kyle T S Pattinson, Ricardo Governo, Bradley J MacIntosh, Elizabeth C Russell, Douglas R Corfield, Irene Tracey, Richard G WiseRespiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensory-affective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem.
History
Publication status
- Published
File Version
- Published version
Journal
Journal of NeuroscienceISSN
1529-2401Publisher
Society for NeurosciencePublisher URL
External DOI
Issue
25Volume
29Page range
8177-8186Department affiliated with
- Clinical and Experimental Medicine Publications
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IDS Number: 462GLFull text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2011-08-24First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2017-03-07Usage metrics
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