Prescription opioid analgesics rapidly change the human brain

Department of Anesthesia, School of Medicine, Stanford University, Palo Alto, CA 94304-1573, USA.
Pain (Impact Factor: 5.21). 04/2011; 152(8):1803-10. DOI: 10.1016/j.pain.2011.03.028
Source: PubMed

ABSTRACT Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.

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Available from: Jarred Younger, Sep 25, 2015
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    • "However, given that only 2 TMD subjects reported migraine as an additional complaint, we are confident that our results reflect underlying changes associated with TMD and not migraine. In addition, it is known that opioid use can rapidly change brain anatomy, in particular in the reward circuitry (Younger et al., 2011). Although only 4 of the TMD subjects in this investigation were taking opioids, most were on some form of medications and it is possible that these could have altered brain anatomy. "
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    ABSTRACT: Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 05/2015; 117. DOI:10.1016/j.neuroimage.2015.05.014 · 6.36 Impact Factor
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    • "Hence, the anterior cingulate cortex has been assumed to play a possibly predominant role in endogen pain control and habituation processing to chronic pain. Additionally, it is an intriguing observation that chronic opioid exposure leads to a dose-dependent gray matter increase in the cingulate cortex [43]. Interestingly, only one of the twelve patients used opioids for the treatment of chronic low back pain. "
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    ABSTRACT: Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the LDH.
    PLoS ONE 03/2014; 9(3):e90816. DOI:10.1371/journal.pone.0090816 · 3.23 Impact Factor
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    • "Previous studies on consumption of opioids in patients with non-cancer pain were either non population-based [1,2], limited to a specific population, such as workers with low back injuries [3-5], or had only a short follow-up [6]. Moreover, studies dealing with concerns of abuse, side effects, and efficacy of long-term opioid therapy in these conditions have not been conclusive [7-9]. "
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    ABSTRACT: The pattern of opioid use after skeletal trauma is a neglected topic in pain medicine. The purpose of this study was to analyse the long-term prescriptions of potent opioids among patients with tibial shaft fractures. Data were extracted from the Swedish National Hospital Discharge Register, the National Pharmacy Register, and the Total Population Register, and analysed accordingly. The study period was 2005-2008. We identified 2,571 patients with isolated tibial shaft fractures. Of these, 639 (25%) collected a prescription for opioids after the fracture. The median follow-up time was 17 (interquartile range [IQR] 7-27) months. Most patients with opioid prescriptions after fracture were male (61%) and the median age was 45 (16-97) years. The leading mechanism of injury was fall on the same level (41%). At 6 and 12 months after fracture, 21% (95% CI 17-24) and 14% (11-17) were still being treated with opioids. Multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that older patients (age >50 years) were more likely to end opioid prescriptions (Hazard ratio 1.5 [95% CI 1.3-1.9]). During follow-up, the frequency of patients on moderate and high doses declined. Comparison of the daily morphine equivalent dose among individuals who both had prescriptions during the first 3 months and the 6th month indicated that the majority of these patients (11/14) did not have dose escalations. We did not see any signs in registry-data of major dose escalations over time in patients on potent opioids after tibial shaft fractures.
    BMC Anesthesiology 01/2014; 14(1):4. DOI:10.1186/1471-2253-14-4 · 1.38 Impact Factor
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