Stiripentol alleviates neuropathic pain in L5 spinal nerve-transected mice

Fujiwara, Atsushi; Nakao, Kenta; Ueno, Takeshi; Matsumura, Shinji; Ito, Seiji; Minami, Toshiaki

doi:10.1007/s00540-020-02762-2

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…At the time of drug administration, behavioral symptoms have already developed suggesting that inhibiting lactate shuttling can reduce pain hypersensitivity during the chronic phase. A study by a separate group also found that 4-CIN could partially alleviate mechanical allodynia during the chronic phase of a spinal-nerve ligation pain model (197). Hence, this initial evidence points to a possible role of spinal astrocytic lactate in maintaining pain hypersensitivity.…”

Section: Initial Research On Astrocyte Lactate Export In Chronic Painmentioning

confidence: 77%

Reactive Astrocytes: Critical Players in the Development of Chronic Pain

2021

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Chronic pain is associated with long term plasticity of nociceptive pathways in the central nervous system. Astrocytes can profoundly affect synaptic function and increasing evidence has highlighted how altered astrocyte activity may contribute to the pathogenesis of chronic pain. In response to injury, astrocytes undergo a shift in form and function known as reactive astrogliosis, which affects their release of cytokines and gliotransmitters. These neuromodulatory substances have been implicated in driving the persistent changes in central nociceptive activity. Astrocytes also release lactate which neurons can use to produce energy during synaptic plasticity. Furthermore, recent research has provided insight into lactate's emerging role as a signaling molecule in the central nervous system, which may be involved in directly modulating neuronal and astrocytic activity. In this review, we present evidence for the involvement of astrocyte-derived tumor necrosis factor alpha in pain-associated plasticity, in addition to research suggesting the potential involvement of gliotransmitters D-serine and adenosine-5′-triphosphate. We also discuss work implicating astrocyte-neuron metabolic coupling, and the possible role of lactate, which has been sparsely studied in the context of chronic pain, in supporting pathological changes in central nociceptive activity.

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Section: Initial Research On Astrocyte Lactate Export In Chronic Painmentioning

confidence: 77%

Reactive Astrocytes: Critical Players in the Development of Chronic Pain

2021

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“…Because of its effects on glucose energy metabolism and lactate dehydrogenase, efficacy of STP was found in other models of diseases including cerebral ischemia [ 71 , 142 ], Alzheimer’s disease [ 77 ], neuropathic pain [ 143 ], and Lyme disease and Borrelia burgdorferi infection [ 144 ]. These studies remain exploratory and, to our knowledge, are not yet supported by clinical data.…”

Section: Discussionmentioning

confidence: 99%

An Update on Stiripentol Mechanisms of Action: A Narrative Review

Bacq,

Depaulis,

Castagné

et al. 2024

Adv Ther

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Stiripentol (Diacomit ® ) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABA A receptors, especially those containing α3 and δ subunits. Blockade of voltage-gated sodium and T-type calcium channels, which is classically associated with anticonvulsant and neuroprotective properties, has also been demonstrated for STP. Finally, several studies indicate that STP could regulate glucose energy metabolism and inhibit lactate dehydrogenase. STP is also an inhibitor of several cytochrome P450 enzymes involved in the metabolism of other ASMs, contributing to boost their anticonvulsant efficacy as add-on therapy. These different MoAs involved in treatment of DS and recent data suggest a potential for STP to treat other neurological or non-neurological diseases.

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“…In addition, it has been reported that STP can reduce seizure severity and seizure-induced neuronal damage in animal models of epilepsy [ 16 - 18 ]. In addition, a recent study has reported the effect of STP against neuropathic pain induced by spinal nerve transection in mice, showing that intrathecal administration with STP can attenuate mechanical hyperalgesia in a dose-dependent manner [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus

Shin

Lee

et al. 2022

Korean J Physiol Pharmacol

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Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

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Stiripentol alleviates neuropathic pain in L5 spinal nerve-transected mice

Cited by 5 publications

References 23 publications

Reactive Astrocytes: Critical Players in the Development of Chronic Pain

Reactive Astrocytes: Critical Players in the Development of Chronic Pain

An Update on Stiripentol Mechanisms of Action: A Narrative Review

Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus

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