Opioids depress cortical centers responsible for the volitional control of respiration

Pattinson, Kyle T S, Governo, Ricardo J, MacIntosh, Bradley J, Russell, Elizabeth C, Corfield, Douglas R, Tracey, Irene and Wise, Richard G (2009) Opioids depress cortical centers responsible for the volitional control of respiration. Journal of Neuroscience, 29 (25). pp. 8177-8186. ISSN 1529-2401

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Abstract

Respiratory 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.

Item Type: Article
Additional Information: IDS Number: 462GL
Keywords: CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; MOTOR CORTEX; BRAIN; ACTIVATION; DYSPNEA; HUMANS; REMIFENTANIL; NETWORK; MODEL
Schools and Departments: Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Tracey O'Gorman
Date Deposited: 24 Aug 2011 14:04
Last Modified: 01 Sep 2017 18:54
URI: http://sro.sussex.ac.uk/id/eprint/7153
Google Scholar:21 Citations

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