Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain

Jiang, Yingying; Cui, Shuang; Liu, Fengyu; Yi, Ming; Wan, You

doi:10.1016/j.neulet.2018.01.041

Cited by 26 publications

(25 citation statements)

References 44 publications

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“…Anxiety can be co-morbid with pain. Indeed, inhibition of septo-cingulate, but not septo-hippocampal cholinergic input attenuates the anxiety induced in animals that had previously experienced persistent experimental pain 60 .…”

Section: Discussionmentioning

confidence: 98%

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Forebrain medial septum sustains experimental neuropathic pain

Ariffin

Ibrahim

Lee

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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Section: Discussionmentioning

confidence: 98%

“…Here it is notable that the MS is the dominant source of cholinergic afferent to the region. The MS cholinergic neurons are implicated in nociception 38 , 59 , 60 . In the present study, muscimol microinjection into the MS, but not the adjacent LS reversed the mechanical and thermal PH after unilateral CCI injury of sciatic nerve.…”

Section: Discussionmentioning

confidence: 99%

Forebrain medial septum sustains experimental neuropathic pain

Ariffin

Ibrahim

Lee

et al. 2018

Sci Rep

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“…[15][16][17] In addition, neuropathic pain also increased apoptosis of hippocampal neurons in rats. 18,19 These evidences suggest that hippocampus is closely related to cognitive impairment in neuropathic pain animal models.…”

Section: Introductionmentioning

confidence: 99%

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

et al. 2020

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Objectives: To explore the effects of trigeminal neuralgia on neurodegeneration in rats and the underlining mechanism. Methods: Sixty adult male Sprague Dawley rats were divided randomly into Chronic Constriction Injury of the Rat's Infraorbital Nerve (ION-CCI) group and sham group (n ¼ 30). Right suborbital nerve was ligated in ION-CCI group to establish a trigeminal neuralgia model. In sham group, suborbital nerve was exposed without ligation. Pain thresholds were measured before surgery and 1, 7, 15, and 30 days after surgery (n ¼ 10). Morris water maze tests (n ¼ 10) were conducted at 1, 15, and 30 days after surgery to evaluate the changes in learning and memory ability of rats. At 5, 19, and 34 days after surgery, serum S100b protein concentration and hippocampal Ab1-42 protein expression were detected by enzyme-linked immunosorbent assay; total tau protein expression was detected by Western blotting; changes of neurons in hippocampus were observed by Nissl staining; and the expression of ser404 p-tau, cluster of differentiation (CD)95, CD95L, and cleaved caspase-3 proteins was detected by immunofluorescence and Western blotting. Results: Hyperalgesia occurred in ION-CCI group, and mechanical pain threshold decreased significantly (P < 0.05). On the 15th and 30th days after surgery, ION-CCI group showed lower learning and memory ability than sham group (P < 0.05). Serum S100b protein concentration, hippocampal A b1-42, and ser404 p-tau protein expression increased in the ION-CCI group 19 and 34 days after surgery (P < 0.05), hippocampal CD95 expression increased in the ION-CCI group after surgery (P < 0.05), hippocampal CD95L expression increased at 19 and 34 days after surgery (P < 0.05), and cleaved caspase-3 expression increased at 5 and 19 days after surgery (P < 0.05). Nissl bodies in ION-CCI group decreased significantly at 15 days after surgery. The expression of cleaved caspase-3 protein in ION-CCI group was positively correlated with the expression of CD95 and CD95L (P < 0.05). Conclusions: Trigeminal neuralgia may lead to neuronal inflammation and neuronal apoptosis associated with upregulation of CD95/CD95L expression, thus causing neurodegeneration.

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“…Cholinergic projections of VDB origin also innervate the substantia innominata (Parent et al, 1988). Cholinergic efferents from MS innervate the posterior cingulate region (Woolf et al, 1984), as well as the rostral anterior cingulate cortex; this latter pathway seems to be involved in maintaining anxiety during chronic pain, independently from the septo-hippocampal pathway (Jiang et al, 2018a(Jiang et al, , 2018b. These fibers form synapses with GABAergic interneurons in the cingulate and retrosplenial cortices (Semba, 2000).…”

Section: Efferent Projections From the Medial Septummentioning

confidence: 99%

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

Takeuchi

Nagy

Barcsai

et al. 2021

Preprint

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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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Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain

Cited by 26 publications

References 44 publications

Forebrain medial septum sustains experimental neuropathic pain

Forebrain medial septum sustains experimental neuropathic pain

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

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

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