Opioid analgesia is limited by the potentially fatal side effect of respiratory depression. In humans the brain mechanisms of opioid-induced respiratory depression are poorly understood. Investigating pharmacological influences upon breathing helps us to understand better the brain's respiratory control networks. Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (FMRI) maps neuronal activity in the brain, and is therefore a potentially useful, noninvasive technique to investigate the functional neuroanatomy of respiratory control in humans. Contrast in FMRI is derived from the vascular response to brain activity (neurovascular coupling). Therefore, FMRI studies of the neuronal effects of opioids are rendered more complex by the nonneuronal effects of opioids including those on systemic physiology, cerebral blood flow, and direct effects on the cerebral vasculature such as altered vascular reactivity. Here we review our series of studies that dissect the vascular and neuronal breathing-related effects of opioids in the brain. These methodological considerations have enabled successful FMRI studies revealing the brain networks responsible for opioid effects upon respiratory awareness. Similar considerations would be necessary for FMRI studies in hypoxia or in disease states that affect the physiological state of the brain.
Keywords: BOLD; CBF; Carbon dioxide; Functional MRI; Respiration.