title: Elevated gamma band power in humans receiving naloxone suggests dorsal periaqueductal and periventricular gray deep brain stimulation produced analgesia is opioid mediated.
abstract: BACKGROUND
  The midbrain periaqueductal and periventricular gray (PAVG) region is important for pain and autonomic modulation. We have previously described changes in blood pressure dependent upon dorsal or ventral electrode positioning with PAVG deep brain stimulation (DBS), yet controversy exists about whether DBS acts via endogenous opioid release.
  
  
  RESULTS
  We combined local field potential (LFP) recording from PAVG DBS electrodes in humans with naloxone and saline infusions to determine whether dorsal and ventral PAVG DBS act through opioidergic or other mechanisms. Four awake human subjects were investigated. DBS were implanted contralateral to the painful body part. Electrode contact positions were mapped using MRI and brain atlas information. Naloxone then saline were randomly administered to the blinded subjects and pain rated using a numeric pain rating scale at 30s intervals for 3 min. Two subjects received dorsal DBS electrodes and two had ventral placements. Significantly elevated gamma frequency band (30-90 Hz) power concomitant with pain exacerbation was found with naloxone versus both saline and rest in dorsal not ventral PAVG LFPs (p<0.005). Significantly elevated delta frequency band (0-4 Hz) power (p=0.001) was seen in one ventral PAVG subject with both naloxone and saline infusions.
  
  
  CONCLUSIONS
  Dorsal PAVG DBS may reduce pain by augmenting endogenous opioid release. Elevated gamma oscillations enhance awareness of worsening pain with opioid blockade. Ventral PAVG DBS may act by separate possibly autonomic mechanisms. Increased delta oscillations indicate a survival rhythm involved in the initiation of passive coping responses to homeostatic changes.
authors.affiliation: Oxford Functional Neurosurgery and Experimental Neurology Group, Nuffield Department of Surgery, University of Oxford and Department of Neurological Surgery, The West Wing, Oxford, UK. eacp@eacp.co.uk
authors.forename: Erlick A C
authors.initials: EA
authors.lastname: Pereira
authors.forename: Shouyan
authors.initials: S
authors.lastname: Wang
authors.forename: Thomas
authors.initials: T
authors.lastname: Peachey
authors.forename: Guohua
authors.initials: G
authors.lastname: Lu
authors.forename: David
authors.initials: D
authors.lastname: Shlugman
authors.forename: John F
authors.initials: JF
authors.lastname: Stein
authors.forename: Tipu Z
authors.initials: TZ
authors.lastname: Aziz
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Green
mesh_terms: D000698:Analgesia; D002552:Cerebral Ventricles / Q000502:physiology*; D003627:Data Interpretation, Statistical; D046690:Deep Brain Stimulation; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D019635:Neurosurgical Procedures; D010487:Periaqueductal Gray / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone