Elevated gamma band power in humans receiving naloxone suggests dorsal periaqueductal and periventricular gray deep brain stimulation produced analgesia is opioid mediated

Pereira, Erlick A. C.; Wang, Shouyan; Peachey, Tom; Lü, Guohua; Shlugman, D.; Stein, John; Aziz, Tipu Z.; Green, Alexander L.

doi:10.1016/j.expneurol.2012.10.017

Cited by 27 publications

(20 citation statements)

References 59 publications

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“…However, the cerebrospinal fluid measures were artifactual [127,128], and double blinded investigation in humans has revealed no cross-tolerance between DBS and morphine and similar reversibility between naloxone and saline placebo [129], confirming others' findings [33,130]. Our human naloxone studies suggest that only dorsal PAG/periventricular gray DBS may be acting via opioidergic mechanisms [131].…”

Section: Physiologysupporting

confidence: 81%

Neuropathic Pain and Deep Brain Stimulation

Pereira

Aziz

2014

Neurotherapeutics

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Deep brain stimulation (DBS) is a neurosurgical intervention the efficacy, safety, and utility of which are established in the treatment of Parkinson's disease. For the treatment of chronic, neuropathic pain refractory to medical therapies, many prospective case series have been reported, but few have published findings from patients treated with current standards of neuroimaging and stimulator technology over the last decade . We summarize the history, science, selection, assessment, surgery, programming, and personal clinical experience of DBS of the ventral posterior thalamus, periventricular/periaqueductal gray matter, and latterly rostral anterior cingulate cortex (Cg24) in 113 patients treated at 2 centers (John Radcliffe, Oxford, UK, and Hospital de São João, Porto, Portugal) over 13 years. Several experienced centers continue DBS for chronic pain, with success in selected patients, in particular those with pain after amputation, brachial plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other successes include pain after multiple sclerosis and spine injury. Somatotopic coverage during awake surgery is important in our technique, with cingulate DBS under general anesthesia considered for whole or hemibody pain, or after unsuccessful DBS of other targets. Findings discussed from neuroimaging modalities, invasive neurophysiological insights from local field potential recording, and autonomic assessments may translate into improved patient selection and enhanced efficacy, encouraging larger clinical trials.

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Section: Physiologysupporting

confidence: 81%

Neuropathic Pain and Deep Brain Stimulation

Pereira

Aziz

2014

Neurotherapeutics

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“…This defense pattern is represented in the dorsomedial and dorsolateral PAG and is classically associated with endogenous nonopioid analgesia, increased ABP, and HR, 29 although recent evidence in humans suggests that it may in fact be opioid mediated. 44 Our results show that in the absence of an external threat, the nerve firing pattern and cardiovascular response to electric stimulation of the dorsolateral PAG for treatment of chronic pain resembles that of arousal and defense pattern, and perhaps this may explain the pain relief.…”

Section: Dorsal Pagmentioning

confidence: 62%

Differentiated Baroreflex Modulation of Sympathetic Nerve Activity During Deep Brain Stimulation in Humans

et al. 2014

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Targeted electric deep brain stimulation in midbrain nuclei in humans alters cardiovascular parameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at 2 distinct brain locations. The aim of this study was to evaluate sympathetic outflow in humans with deep brain stimulating electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Multiunit muscle sympathetic nerve activity was recorded in 17 patients undergoing deep brain stimulation for treatment of chronic neuropathic pain (n=7) and Parkinson disease (n=10). Sympathetic outflow was recorded during ON and OFF stimulation. Arterial blood pressure, heart rate, and respiratory frequency were monitored during the recording session, and spontaneous vasomotor and cardiac baroreflex sensitivity were assessed. Head-up tilt testing was performed separately in the patients with Parkinson disease postoperatively. Stimulation of the dorsal most part of the subthalamic nucleus and ventrolateral periaqueductal gray resulted in improved vasomotor baroreflex sensitivity, decreased burst frequency and blood pressure, unchanged burst amplitude distribution, and a reduced fall in blood pressure after tilt. Stimulation of the dorsolateral periaqueductal gray resulted in a shift in burst amplitude distribution toward larger amplitudes, decreased spontaneous beat-to-beat blood pressure variability, and unchanged burst frequency, baroreflex sensitivity, and blood pressure. Our results indicate that a differentiated regulation of sympathetic outflow occurs in the subthalamic nucleus and periaqueductal gray. These results may have implications in our understanding of abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting.

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“…4 The mechanisms of action of DBS for chronic pain are not yet clear, but it has been proposed that PAG DBS may exert its effects through opioidergic or autonomic mechanisms in the pain neuromatrix. 5 On the other hand, VP stimulation may work through nonopioid mechanisms and is therefore more likely to be useful for central pain. 6 Combined electrical stimulation of PAG and VP has been used to synergistically optimize chances of reaching good pain relief.…”

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confidence: 99%