Pain Relief by Electrical Stimulation of the Central Gray Matter in Humans and Its Reversal by Naloxone

Hosobuchi, Yoshio; Adams, John E.; Linchitz, Rita

doi:10.1126/science.301658

Cited by 689 publications

(157 citation statements)

References 31 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…Alongside the sensory thalamus, they have become the main anatomic targets for deep brain stimulation (DBS) for chronic neuropathic pain over 4 decades [2,3,4,5,6]. The procedure demonstrates good efficacy for an otherwise refractory group with approximately two thirds of patients gaining pain relief sustained for several years in aetiologies of amputation including phantom limb pain, brachial plexus avulsion, and face and head pain including anaesthesia dolorosa and post-stroke pain not affecting the whole body [7,8,9].…”

Section: Introductionmentioning

confidence: 99%

Human Periventricular Grey Somatosensory Evoked Potentials Suggest Rostrocaudally Inverted Somatotopy

Pereira

Wang

Owen

et al. 2013

Stereotact Funct Neurosurg

View full text Add to dashboard Cite

Background: Somatosensory homunculi have been demonstrated in primary somatosensory cortex and ventral posterior thalamus but not periaqueductal and periventricular grey matter (PAVG), a therapeutic target for deep brain stimulation (DBS) in chronic pain. Aims: The study is an investigation of somatotopic representation in PAVG and assessment for a somatosensory homunculus. Methods: Five human subjects were investigated using electrical somatosensory stimulation and deep brain macroelectrode recording. DBS were implanted in the contralateral PAVG. Cutaneous arm, leg and face regions were stimulated while event-related potentials were recorded from deep brain electrodes. Electrode contact positions were mapped using MRI and brain atlas information. Results: Monopolar P1 somatosensory evoked potential amplitudes were highest and onset latencies shortest in contralateral caudal PAVG with facial stimulation and rostral with leg stimulation, in agreement with reported subjective sensation during intra-operative electrode advancement. Conclusions: A rostrocaudally inverted somatosensory homunculus exists in the human PAVG region. Objective human evidence of PAVG somatotopy increases understanding of a brainstem region important to pain and autonomic control that is a clinical target for both pharmacological and neurosurgical therapies. Such knowledge may assist DBS target localisation for neuropathic pain syndromes related to particular body regions like brachial plexopathies, anaesthesia dolorosa and phantom limb pain.

show abstract

Section: Introductionmentioning

confidence: 99%

Human Periventricular Grey Somatosensory Evoked Potentials Suggest Rostrocaudally Inverted Somatotopy

Pereira

Wang

Owen

et al. 2013

Stereotact Funct Neurosurg

View full text Add to dashboard Cite

show abstract

“…The characteristics of the pain relief obtained from such stimulation have been described (32,33). This stimulation-induced analgesia in man also appears to have an opioid component, because it has been shown to be naloxone reversible (34,35) and to be accompanied by a rise in enkephalin-like opioid material in the cerebrospinal fluid (CSF) (36). Because planted in the chest pectoralis region.…”

mentioning

confidence: 99%

Appearance of beta-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation.

Akil¹,

Richardson²,

Barchas³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

150

View full text Add to dashboard Cite

jt-Endorphin-like immunoreactivity in human ventricular cerebrospinal fluid was measured with a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation of a medial thalamic site adjacent to the wall of the third ventricle. Samples were collected before and during the analgesic stimulation. No f-endorphin-like immunoreactivity could be detected prior to stimulation, suggesting that baseline levels are below 25 fmol/ml of cerebrospinal fluid. Electrical stimulation led to substantial increases (13-to 20-fold) in immunoreactive material in every subject. These results suggest that ,kendorphin-like material can be released into the ventricular system and may contribute to the pain blockade that results from periventricular stimulation.The isolation and characterization of f3-endorphin from camel (1), sheep (2), and human (2, 3) pituitaries rapidly led to its identification as an endogenous opioid (1-4). Administration of this 31-amino-acid peptide to laboratory animals results in phenomena like those associated with opiates, including naloxone-reversible analgesia (5-10), tolerance (8-11), and dependence (8,11 Electrical stimulation of the brain has been shown to elicit analgesia in rat (26) and cat (27). This analgesia bears many of the characteristics of opiate action, including partial reversal with the opiate antagonist naloxone (28-30) and the development of tolerance to and cross-tolerance with morphine (31). However, these effects are only partial, suggesting a role of nonopiate as well as opiate mechanisms in this method of pain control. This work has been extended to the human clinical situation. Patients suffering from chronic intractable pain derive long-term relief from the stimulation of medial thalamic and periaqueductal sites (32,33). Stimulation of a site in the vicinity of the posterior commissure, immediately adjacent to the ventricular wall at the level of the nucleus parafascicularis, has been found to combine excellent analgetic effectiveness with minimal side effects. The characteristics of the pain relief obtained from such stimulation have been described (32,33). This stimulation-induced analgesia in man also appears to have an opioid component, because it has been shown to be naloxone reversible (34, 35) and to be accompanied by a rise in enkephalin-like opioid material in the cerebrospinal fluid (CSF) (36). Because the stimulation site in humans is homologous to a region in rodents particularly rich in (3-endorphin activity, we have examined the effect of its stimulation on (3-endorphin immunoreactivity in CSF. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. METHODS

show abstract

“…By the 1970s, several centres were performing DBS for neuropathic pain. Evidence for targeting PVG/PAG came from pain relief in rodents during awake surgery [77,78], and human studies followed [79,80,81,82]. Evidence for targeting the thalamic nuclei (VPL/VPM) came from ablative surgery [83,84,85], with subsequent human studies [86,87,88,89,90], along with Adams, who also targeted the internal capsule [91,92,93], moving to more medial targets developed from localisation errors and investigations in the current spread [94,95,96,97].…”

Section: Management Of Chronic Painmentioning

confidence: 99%

The Current State of Deep Brain Stimulation for Chronic Pain and Its Context in Other Forms of Neuromodulation

2018

View full text Add to dashboard Cite

Chronic intractable pain is debilitating for those touched, affecting 5% of the population. Deep brain stimulation (DBS) has fallen out of favour as the centrally implantable neurostimulation of choice for chronic pain since the 1970–1980s, with some neurosurgeons favouring motor cortex stimulation as the ‘last chance saloon’. This article reviews the available data and professional opinion of the current state of DBS as a treatment for chronic pain, placing it in the context of other neuromodulation therapies. We suggest DBS, with its newer target, namely anterior cingulate cortex (ACC), should not be blacklisted on the basis of a lack of good quality study data, which often fails to capture the merits of the treatment.

show abstract

Pain Relief by Electrical Stimulation of the Central Gray Matter in Humans and Its Reversal by Naloxone

Cited by 689 publications

References 31 publications

Human Periventricular Grey Somatosensory Evoked Potentials Suggest Rostrocaudally Inverted Somatotopy

Human Periventricular Grey Somatosensory Evoked Potentials Suggest Rostrocaudally Inverted Somatotopy

Appearance of beta-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation.

The Current State of Deep Brain Stimulation for Chronic Pain and Its Context in Other Forms of Neuromodulation

Contact Info

Product

Resources

About