Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system

Fonoff, Erich Talamoni; Dale, Camila S.; Pagano, Rosana L.; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

doi:10.1016/j.bbr.2008.07.027

Cited by 72 publications

(64 citation statements)

References 44 publications

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“…The only plausible explanation that has been suggested for the effect of MCS is that it acts as a descending modulator. 12,27 More studies are required to understand the relationship between MCS and neuropathic pain. We hypothesized that MCS acts as not only a descending modulator but also an ascending modulator of pain pathways.…”

Section: Fig 5 Comparison Of the Behavioral Test Results Between Ipmentioning

confidence: 99%

“…1) 26,32 that covers the hindlimb area of the right primary motor cortex. 12 One week after pain induction surgery, rats were anesthetized using pentobarbital sodium (50 mg/kg, intraperitoneally) and fixed using a stereotactic frame (Narishige). We then opened each rat's scalp to expose the skull.…”

Section: Electrical Stimulationmentioning

confidence: 99%

“…We then opened each rat's scalp to expose the skull. To place the electrode on the region of the primary motor cortex that controls the right hindlimb area, 12,36 we made a small rectangular opening to expose the dura (2.0 mm × 2.0 mm). The coordinates were -0.2 to +1.8 mm from bregma and 0.5 to 2.5 mm from the midline.…”

Section: Electrical Stimulationmentioning

confidence: 99%

“…Fonoff et al 12 and Lucas et al 27 hypothesized that MCS stimulates serotonin secretion in the periaqueductal gray (PAG) directly, or indirectly via the zona incerta (ZI). Therefore, we expected to observe changes in serotonin levels in the spinal cord.…”

Section: How Does Mcs Affect the Descending Pathway?mentioning

confidence: 99%

“…MCS probably acts via the primary motor cortex (M1), which modulates the thalamic area or zona incerta (ZI) via direct or indirect pathways, and the thalamic area and the ZI modulate the secretion of opioids or serotonin. 12 Detailed studies of the action mechanism of MCS and its ability to modulate pain are urgently required.…”

mentioning

confidence: 99%

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Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

Kim

Ryu

Lee

et al. 2016

JNS

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N europathic pain is often severe, and it can afflict patients for their entire lifetime. It can be caused by direct damage to the nervous system, and by neuronal degeneration. 7,8 Patients with degenerative diseases such as Parkinson's disease or dementia may experience neuropathic pain as a complication. Many studies have found that neuropathic pain can be induced by indirect nerve damage, but the mechanisms have not yet been clearly established. 7,8,29 The symptoms of neuropathic pain differ among patients, making treatment difficult.31 Although many studies of neuropathic pain and its control have been conducted, the mechanisms behind neuropathic pain are still not clear.Motor cortex stimulation (MCS) is a treatment modality used to modulate neuropathic pain by electrical stimulation. It was introduced in 1991 by Tsubokawa et al. and has since been used in clinical practice.46,47 MCS has advantages for clinicians and patients: MCS is simpler and easier to implement for pain modulation than other surgical methods, such as direct nerve stimulation and neurectomy, and can be considered an alternative for pain control. Among the many modalities involving electrical obJective Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. methods Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. results MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. coNclusioNs This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

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Section: Fig 5 Comparison Of the Behavioral Test Results Between Ipmentioning

confidence: 99%

Section: Electrical Stimulationmentioning

confidence: 99%

Section: Electrical Stimulationmentioning

confidence: 99%

Section: How Does Mcs Affect the Descending Pathway?mentioning

confidence: 99%

mentioning

confidence: 99%

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Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

Kim

Ryu

Lee

et al. 2016

JNS

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From pulses to pain relief: an update on the mechanisms of rTMS‐induced analgesic effects

Moisset

Andrade

Bouhassira

2015

European Journal of Pain

123

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Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. Databases: Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. Results: Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. Conclusions: rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action.

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Motor Cortex Stimulation: Neural Circuits and Practical Approach on Electrode Implantation Technique

Fonoff

Azevedo

Alho

2021

Neuromodulation Techniques for Pain Treatment

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Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system

Cited by 72 publications

References 44 publications

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

From pulses to pain relief: an update on the mechanisms of rTMS‐induced analgesic effects

Motor Cortex Stimulation: Neural Circuits and Practical Approach on Electrode Implantation Technique

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