Analgesia from Electrical Stimulation in the Brainstem of the Rat

Mayer, David J.; Wolfle, Thomas L.; Akil, Huda; Carder, Brooks; Liebeskind, John C.

doi:10.1126/science.174.4016.1351

Cited by 709 publications

(173 citation statements)

References 11 publications

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“…For instance, studies suggest that stimulation of specific regions of the midbrain, PAG and surrounding areas could inhibit pain responses to noxious stimulation in both animal studies [27,35] and patients suffering from pain disorders [1,10]. It has been hypothesized that acupuncture may somehow trigger this descending inhibition system to produce an analgesic effect.…”

Section: Discussionmentioning

confidence: 99%

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

Dougherty

Kong

Webb

et al. 2008

Behavioural Brain Research

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Functional neuroimaging studies suggest that a lateral network in the brain is associated with the sensory aspects of pain perception while a medial network is associated with affective aspects. The highest concentration of opioid receptors is in the medial network. There is significant evidence that endogenous opioids are central to the experience of pain and analgesia. We applied an integrative multimodal imaging approach during acupuncture. We found functional magnetic resonance imaging signal changes in the orbitofrontal cortex, insula, and pons and [11C]diprenorphine positron emission tomography signal changes in the orbitofrontal cortex, medial prefrontal cortex, insula, thalamus, and anterior cingulate cortex. These findings include brain regions within both the lateral and medial pain networks.

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Section: Discussionmentioning

confidence: 99%

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

Dougherty

Kong

Webb

et al. 2008

Behavioural Brain Research

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show abstract

“…Reynolds and others were able to perform major surgery in awake rodents using analgesia induced by PAG stimulation alone [13,14]. Pain relief by PAG DBS was first reported in patients by Richardson and Akil, and then Hosobuchi [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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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“…It is well established that electrical stimulation of portions of the medial brainstem can inhibit both vocalization to nociceptive stimuli and spinally mediated nociceptive reflexes (Reynolds 1969;Mayer et al 1971;Oliveras et al 1974;Akil and Liebeskind 1975;Basbaum et al 1977;Basbaum and Fields 1979). The inhibitory signal, is believed to originate in the periaqueductal gray, travel to the rostroventral medulla, including the nucleus raphe magnus (NRM), and then to the spinal cord through serotonergic fibers that descend through the DLF to suppress firing of neurons within the dorsal horns (Mayer et al 1971;Oliveras et al 1974;Fields 1979, 1984). This antinociceptive system can be engaged by aversive environmental stimuli, such as shock and restraint (Madden et al 1977;Terman et al 1984;Tricklebank and Curzon 1984).…”

Section: Introductionmentioning

confidence: 99%

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

et al. 2007

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Rationale-Spinal cord plasticity can be assessed in spinal rats using an instrumental learning paradigm in which subjects learn an instrumental response, hindlimb flexion, to minimize shock exposure. Prior exposure to uncontrollable intermittent stimulation blocks learning in spinal rats but has no effect if given before spinal transection, suggesting that supraspinal systems modulate nociceptive input to the spinal cord, rendering it less susceptible to the detrimental consequences of uncontrollable stimulation.Objective-The present study examines whether disrupting brain function with pentobarbital blocks descending inhibitory systems that normally modulate nociceptive input, making the spinal cord more sensitive to the adverse effect of uncontrollable intermittent stimulation. Materials and methods-MaleSprague-Dawley rats received uncontrollable intermittent stimulation during pentobarbital anesthesia after (experiment 1) or before (experiment 2) spinal cord transection. They were then tested for instrumental learning at a later time point. Experiment 3 examined whether these manipulations affected nociceptive (thermal) thresholds.Results-Experiment 1 showed that pentobarbital had no effect on the induction of the learning deficit after spinal cord transection. Experiment 2 showed that intact rats anesthetized during uncontrollable intermittent stimulation failed to learn when later transected and tested for instrumental learning. Experiment 3 found that uncontrollable intermittent stimulation induced an antinociception in intact subjects that was blocked by pentobarbital. Conclusions-The results suggest a surgical dose of pentobarbital (50 mg/kg) suppresses supraspinal (experiment 2) but not spinal (experiment 1) systems that modulate nociceptive input to the spinal cord by blocking the antinociception that is induced by this input (experiment 3).

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Analgesia from Electrical Stimulation in the Brainstem of the Rat

Cited by 709 publications

References 11 publications

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

Neuropathic Pain and Deep Brain Stimulation

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

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