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Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)833-842
Number of pages10
JournalNeuroImage
Volume146
Early online date21 Aug 2016
DOIs
DateAccepted/In press - 18 Aug 2016
DateE-pub ahead of print - 21 Aug 2016
DatePublished (current) - 1 Feb 2017

Abstract

Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or anaesthesia dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400 ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit.

    Research areas

  • Deep Brain Stimulation, Positron Emission Tomography, Pain, Endogenous Opioid, Periaqueductal gray, De-afferentation

    Structured keywords

  • Brain and Behaviour

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  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via Elsevier at http://dx.doi.org/10.1016/j.neuroimage.2016.08.038. Please refer to any applicable terms of use of the publisher.

    Final published version, 1.84 MB, PDF document

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Elsevier at http://www.sciencedirect.com/science/article/pii/S1053811916304220. Please refer to any applicable terms of use of the publisher.

    Final published version, 361 KB, PDF document

    Licence: CC BY

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