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: 5.84). 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, Jul 27, 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
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    • "However, it remains unclear whether these findings from neuroimaging (PET or MRI) studies relate to chronic pain or to effects from long-term medication use (including opioids). The issue was partly addressed in a recent longitudinal MR study (Younger et al., 2011). Individuals with chronic low back pain were administered oral morphine daily for 1 month, and compared to those who used placebo. "
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    ABSTRACT: Opioids play an important role for the management of acute pain and in palliative care. The role of long-term opioid therapy in chronic non-malignant pain remains unclear and is the focus of much clinical research. There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. In this review, we discuss how far human neuroimaging research has come in providing a mechanistic understanding of pain relief provided by opioids, and suggest avenues for further studies that are relevant to the management of chronic pain with opioids. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’.
    Neuropharmacology 07/2013; 84(100). DOI:10.1016/j.neuropharm.2013.06.035
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    • "Ce phénomène d'hyperalgésie peut être induit que les morphiniques soient administrés avant l'inflammation chirurgicale (douleur chronique préopératoire) ou après (douleur aiguë postopératoire) [18]. Les études d'imageries fonctionnelles montrent que les changements induits par l'introduction des morphiniques surviennent dans le premier mois du traitement [19]. En conséquence, tout patient sous opioïdes doit être considéré comme à risque de douleur accrue par ce phénomène d'hyperalgésie et, également, à risque de syndrome de sevrage [20]. "
    Le Praticien en Anesthésie Réanimation 06/2013; 17(3):140-146. DOI:10.1016/j.pratan.2013.04.003
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