Septal stimulation inhibits spinal cord dorsal horn neuronal activity

Hagains, Christopher E.; He, Ji; Chiao, J.-C.; Peng, Yuan Bo

doi:10.1016/j.brainres.2011.01.074

“…Interestingly, while the current findings suggest that inhibition of population of septal neurons with muscimol or attenuation of excitatory transmission through the region is antinociceptive, others reports indicate that high frequency electrical stimulation (HFS) of the septal region, presumably by exciting septal neurons and/or fibers in the region, is also antinociceptive in both anaesthetized and behaving animals 69 – 72 . The reasons for antinociception with divergent techniques are not clear.…”

Section: Discussionmentioning

confidence: 49%

Forebrain medial septum sustains experimental neuropathic pain

Ariffin

¹

,

Ibrahim

²

,

Lee

³

et al. 2018

Sci Rep

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The present study explored the role of the medial septal region (MS) in experimental neuropathic pain. For the first time, we found that the MS sustains nociceptive behaviors in rodent models of neuropathic pain, especially in the chronic constriction injury (CCI) model and the paclitaxel model of chemotherapy-induced neuropathic pain. For example, inactivation of the MS with intraseptal muscimol (2 μg/μl, 0.5 μl), a GABA mimetic, reversed peripheral hypersensitivity (PH) in the CCI model and induced place preference in a conditioned place preference task, a surrogate measure of spontaneous nociception. The effect of intraseptal muscimol on PH was comparable to that seen with microinjection of the local anesthetic, lidocaine, into rostral ventromedial medulla which is implicated in facilitating experimental chronic nociception. Cellular analysis in the CCI model showed that the MS region sustains nociceptive gain with CCI by facilitating basal nociceptive processing and the amplification of stimulus-evoked neural processing. Indeed, consistent with the idea that excitatory transmission through MS facilitates chronic experimental pain, intraseptal microinjection of antagonists acting at AMPA and NMDA glutamate receptors attenuated CCI-induced PH. We propose that the MS is a central monitor of bodily nociception which sustains molecular plasticity triggered by persistent noxious insult.

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“…Importantly, DBS of the MS in humans was found effective to relieve chronic pain (see section “Roles of the MS in Physiological Oscillations”). The exact pathway responsible for this analgesic remains unclear; however, the descending inhibitory pathway from the MS to the dorsal horn neurons of the spinal cord via the raphe nucleus may play a key role ( Hagains et al, 2011 ).…”

Section: Anatomy Of the Medial Septummentioning

confidence: 99%

The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies

Takeuchi

¹

,

Nagy

²

,

Barcsai

³

et al. 2021

Front. Neural Circuits

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The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

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“…Importantly, DBS of the MS in humans was found effective to relieve chronic pain (see section 3). The exact pathway responsible for this analgesic remains unclear; however, the descending inhibitory pathway from the MS to the dorsal horn neurons of the spinal cord via the raphe nucleus may play a key role (Hagains et al, 2011).…”

Section: Efferent Projections From the Medial Septummentioning

confidence: 99%

“…On the other hand, the MS controls exaggerated pain. Importantly, it is known that electrical stimulation of the MS inhibited the firing rate of wide dynamic range neurons in the spinal cord dorsal horn evoked by the peripheral noxious stimulation (pressure, pinch, heat) in anesthetized rats and cats (Carstens et al, 1982;Hagains et al, 2011). Those analgesic effects induced by the MS electrical stimulation are supposed to be mediated by activation of the descending pain inhibitory system.…”

Section: Painmentioning

confidence: 99%

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The Medial Septum as a Potential Target for Treating Brain Disorders Associated with Oscillopathies

Takeuchi

¹

,

Nagy

²

,

Barcsai

³

et al. 2021

Preprint

View full text Add to dashboard Cite

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

show abstract

Septal stimulation inhibits spinal cord dorsal horn neuronal activity

Cited by 11 publications

References 46 publications

Forebrain medial septum sustains experimental neuropathic pain

Forebrain medial septum sustains experimental neuropathic pain

The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies

The Medial Septum as a Potential Target for Treating Brain Disorders Associated with Oscillopathies

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