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

Sims-Williams, Hugh, Matthews, Julian C., Talbot, Peter S., Love-Jones, Sarah, Brooks, Jonathan C. W. ORCID:, Patel, Nikunj K. and Pickering, Anthony E. (2017) Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans. NeuroImage, 146. pp. 833-842. ISSN 1053-8119

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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.

Item Type: Article
Additional Information: Funding Information: HS-W was supported by an Elizabeth Blackwell Institute Clinician Science Primer award from the University of Bristol. AEP is a Wellcome Trust Senior Clinical Research Fellow (gr088373).
Uncontrolled Keywords: de-afferentation,deep brain stimulation,endogenous opioid,pain,periaqueductal gray,positron emission tomography,neurology,cognitive neuroscience ,/dk/atira/pure/subjectarea/asjc/2800/2808
Faculty \ School: Faculty of Social Sciences > School of Psychology
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 11:30
Last Modified: 21 Oct 2022 01:35
DOI: 10.1016/j.neuroimage.2016.08.038

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