Academic literature on the topic 'FMRI opioid'

AbstractBackground and purposeOpioids are potent analgesics. Opioids exert effects after interaction with opioid receptors. Opioid receptors are present in the peripheral- and central nervous system (CNS), but the analgesic effects are primarily mediated via receptors in the CNS. Objective methods for assessment of opioid effects may increase knowledge on the CNS processes responsible for analgesia. The aim of this review was to provide an overview of the most common objective methods for assessment of the spinal and supraspinal effects of opioids and discuss their advantages and limitations.MethodThe literature search was conducted in Pub Med (http://www.ncbi.nlm.nih.gov/pubmed) from November 2014 to June 2016, using free-text terms: “opioid”, “morphine” and “oxycodone” combined with the terms “pupillometry,” “magnetic resonance spectroscopy,” “fMRI,” “BOLD,” “PET,” “pharmaco-EEG”, “electroencephalogram”, “EEG,” “evoked potentials,” and “nociceptive reflex”. Only original articles published in English were included.ResultsFor assessment of opioid effects at the supraspinal level, the following methods are evaluated: pupillometry, proton magnetic resonance spectroscopy, functional resonance magnetic imaging (fMRI), positron emission tomography (PET), spontaneous electroencephalogram (EEG) and evoked potentials (EPs). Pupillometry is a non-invasive tool used in research as well as in the clinical setting. Proton magnetic resonance spectroscopy has been used for the last decades and it is a non-invasive technique for measurement of in vivo brain metabolite concentrations. fMRI has been a widely used non-invasive method to estimate brain activity, where typically from the blood oxygen level-dependent (BOLD) signal. PET is a nuclear imaging technique based on tracing radio labeled molecules injected into the blood, where receptor distribution, density and activity in the brain can be visualized. Spontaneous EEG is typically quantified in frequency bands, power spectrum and spectral edge frequency. EPs are brain responses (assessed by EEG) to a predefined number of short phasic stimuli. EPs are quantified by their peak latencies and amplitudes, power spectrum, scalp topographies and brain source localization.For assessment of opioid effects at the spinal level, the following methods are evaluated: the nociceptive withdrawal reflex (NWR) and spinal EPs. The nociceptive withdrawal reflex can be recorded from all limbs, but it is standard to record the electromyography signal at the biceps femoris muscle after stimulation of the ipsilateral sural nerve; EPs can be recorded from the spinal cord and are typically recorded after stimulation of the median nerve at the wrist.Conclusion and ImplicationsThe presented methods can all be used as objective methods for assessing the centrally mediated effects of opioids. Advantages and limitations should be considered before implementation in drug development, future experimental studies as well as in clinical settings. In conclusion, pupillometry is a sensitive measurement of opioid receptor activation in the CNS and from a practical and economical perspective it may be used as a biomarker for opioid effects in the CNS. However, if more detailed information is needed on opioid effects at different levels of the CNS, then EEG, fMRI, PET and NWR have the potential to be used. Finally, it is conceivable that information from different methods should be considered together for complementary information.

The aims of this study were to assess the effects of a μ-opioid antagonist, naloxone, on endogenous opioid systems and to evaluate the effect of naloxone on the CNS response to mild noxious heat. Doubled-blinded experiments were performed in a cross-over design in 10 healthy male volunteers. Functional magnetic resonance imaging (fMRI) data were collected before and during the infusion and also during thermal stimuli. Increased signal was observed in a number of cortical and subcortical brain regions for naloxone versus saline infusion. Cortical activation was induced in regions including cingulate, prefrontal cortex, and insula. Subcortical regions showing increased signal change included hippocampus and entorhinal cortex. A 46°C stimulus delivered to the back of the hand induced an overall increase in activation in a number of regions in the naloxone group that were not seen in the saline group (e.g., insula, orbitofrontal cortex, thalamus, and hippocampus). These results show that naloxone, even in the absence of psychophysical effects, produces activation in several brain regions that are known to have high levels of μ-opioid receptors and may be involved in endogenous analgesia. Our study is an example of how fMRI can measure subtle changes in brain activation induced by pharmacological agents without cognitive effects.

Abstract Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify μ-opioid receptor and type 2 dopamine receptor (MOR and D2R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D2R availability—here reliably quantified only in striatum—was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.

Connectome genetics seeks to uncover how genetic factors shape brain functional connectivity; however, the causal impact of a single gene’s activity on whole-brain networks remains unknown. We tested whether the sole targeted deletion of the mu opioid receptor gene (Oprm1) alters the brain connectome in living mice. Hypothesis-free analysis of combined resting-state fMRI diffusion tractography showed pronounced modifications of functional connectivity with only minor changes in structural pathways. Fine-grained resting-state fMRI mapping, graph theory, and intergroup comparison revealed Oprm1-specific hubs and captured a unique Oprm1 gene-to-network signature. Strongest perturbations occurred in connectional patterns of pain/aversion-related nodes, including the mu receptor-enriched habenula node. Our data demonstrate that the main receptor for morphine predominantly shapes the so-called reward/aversion circuitry, with major influence on negative affect centers.

Abstract Background The neurobiological mechanisms underlying anhedonia and other negative symptoms in schizophrenia are unknown. Understanding this would help identify treatments for these symptoms. Pre-clinical and human evidence shows the mu-opioid receptor plays a key role in reward processing and anhedonia. However, the contribution of Mu Opioid Receptor (MOR) signalling to negative symptoms and the reward processing abnormalities in schizophrenia is unknown. Here, we investigated for the first time in vivo in patients whether MOR availability is altered in schizophrenia and if this is associated with the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging. Methods Forty volunteers (n=20 patients with schizophrenia and 20 age and sex-matched healthy controls) received an [11C]-carfentanil PET scan to measure MOR availability, a structural MRI scan and a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. All the patients met criteria for persistent negative symptoms. Our primary ROI for the PET analysis was the striatum. In addition, we analysed MOR availability in brain regions in the hedonic network (the striatum, insula and anterior cingulate cortex). The fMRI analysis focused on brain regions in this hedonic network as these have previously associated with MOR mediated reward processing in humans and preclinical studies. Brain volumes of regions of interest (ROIs) were also extracted. Results The analysis showed significantly lower MOR availability in the striatum of patients with schizophrenia relative to controls (patients vs. controls (mean binding potential (BPND) ± SEM): 1.54 ± 0.06 vs. 1.7 ± 0.05, Cohen’s d= 0.7, t=-2.2, df (37), p<0.05). There was also a significant effect of both group (F (5, 222) = 334.5, p<0.05) and ROI (F (1, 222) = 5.65, p<0.05) on BPND measures in the hedonic brain network. The group* ROI interaction was not significant (F (5, 222) = 0.2167, p>0.05). There were no significant differences in the volume of the striatum or other brain regions between groups (patients vs controls: mean ± SEM (mm3) 13019 ± 302 vs 12937 ± 327 respectively, p = 0.86). Reward anticipation in controls was associated with increased neural activation in a widespread network of brain regions including the ventral striatum and insula. The activation in the ventral striatum was significantly lower in patients compared to healthy controls. MOR availability was positively correlated with neural activation in the insula during reward anticipation in controls (spearman’s rho=0.6, p=0.006) but not in patients (spearman’s rho=0.13, p=0.57). In contrast, MOR availability in the striatum was not associated with neural activation in the striatum. Discussion These data show for the first time in vivo that mu-opioid receptor availability is lower in schizophrenia across the hedonic brain network. Moreover, patients with schizophrenia show altered coupling between mu-opioid signalling in the insula and brain activation during reward anticipation. These findings identify the mu-opioid receptor as a potential therapeutic target for reward dysfunction in schizophrenia.

This chapter addresses the situation of opioid users aged 45 and over in Germany, and considers aspects such as the health-related and social characteristics of this group, as well as indicators for the provision of professional support regarding treatment and recovery. The chapter presents findings from the Alters-CM3 research project, which was conducted in Germany between 2014 and 2017. Alters-CM3 is a German abbreviation for ‘Case management for older opioid users in three German regions’. Funded by the Federal Ministry of Research and Education (FMRE), the research focused on practitioners' experiences of implementing a psychosocial intervention specifically adapted for older opioid users; the intervention applied a person-centred case-management approach. In addition, the research considered the implications of the findings for older opioid users' long-term recovery in relation to their life satisfaction and the improvement of psychosocial support.