Spinal GABA mechanism in neuropathic pain after spinal cord injury

Gwak, Young Seob; Luo, Z. David

doi:10.1016/b978-0-12-818662-6.00009-1

Cited by 3 publications

(4 citation statements)

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“…Pain perception is associated with various neurotransmitters, which can be broadly divided into inflammatory and noninflammatory mediators (Gwak and Luo, 2022). Spinal cord injury (SCI) disrupts inhibitory output, sensitising spinal dorsal horn excitatory neurons and increasing nociceptive transmission.…”

Section: Discussionmentioning

confidence: 99%

“…GABA is a key inhibitory neurotransmitter hypothesised to be important in spinal inhibitory synaptic transmission. Therefore, disruptions in GABAergic inhibitory output cause neuronal hyperexcitability in the spinal dorsal horn and chronic NP after SCI (Gwak et al, 2006; Gwak and Luo, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Several reports document that the most specific neurotransmitters in NP are glutamate and GABA, being neuroexcitatory and inhibitory, respectively (Gwak and Luo, 2022). GABAergic precursor cell transplantation fixes allodynia in a mouse NP model (Bráz et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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The gut microbiota-neuroimmune crosstalk and neuropathic pain: a scoping review

Nawarathna,

Fakhruddin,

Shorbagi

et al. 2023

Gut. Microb.

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Environmental stressors can disrupt the gut–brain relationship and alter the gut microbial composition, potentially leading to chronic pain, including neuropathic pain (NP). To understand this complex relationship, we conducted a systematic scoping review to examine the gut microbial-neuroimmune connection to NP and the potential therapeutic targets. The review includes English-language manuscripts in databases such as MEDLINE, Cochrane, and DOAJ between January 2000 and April 2022. Out of the 48 full texts examined, only 15 articles met the inclusion criteria. These included a randomised controlled trial involving 327 individuals, an in vitro, and 13 animal model studies. The findings suggest that the gut flora plays a role in the immunological, neurological, and metabolic signalling pathways associated with NP. Animal studies have been the primary focus in this area, indicating that an imbalanced-gut microbiome and subsequent activation of biochemical and neuro-immunologic pathways may influence the development of NP. This review provides a comprehensive summary of the gut microbiome-immune-NP axis and identifies potential therapeutic targets. However, since most of the evidence comes from animal studies, future research should include clinical trials to gain a better understanding of the role of gut microbiota in NP and discover new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The gut microbiota-neuroimmune crosstalk and neuropathic pain: a scoping review

Nawarathna,

Fakhruddin,

Shorbagi

et al. 2023

Gut. Microb.

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“…An astrocyte is a major cell that makes up the spinal cord; the ratio of astrocytes to neurons is about 10:1 (13,14). Astrocytes are the most important cells for Glu recycling and play a key role in maintaining Glu concentration in the spinal cord (33,34). Unlike neurons, astrocytes have the ability to proliferate and are the most important cells in spinal regeneration.…”

Section: Discussionmentioning

confidence: 99%

Protective role of muscones on astrocytes under a mechanical-chemical damage model

Li¹,

Gui²,

Yu³

et al. 2022

Ann Transl Med

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Background Traumatic spinal cord injury (SCI) is a major clinical concern and a life-changing neurological condition with substantial socioeconomic implications. The initial mechanical force applied to the spinal cord at the time of injury is known as the primary injury. After the primary injury, ischemia and hypoxia induce cell death and autolysis, which are associated with the release of a group of inflammatory factors and biologically active substances, such as superoxide dismutase (SOD), malonaldehyde (MDA), lactate dehydrogenase (LDH), and tumor necrosis factor-α (TNF-α). These processes are called the secondary injury, and may lead to an excess of extracellular glutamate (Glu), which in turn promotes the neuronal injuries. Muscone has been shown to have anti-inflammatory effects in the treatment of brain diseases and other diseases. However, to date, no study has examined the effects of muscone in the treatment of SCI. Methods Astrocytes were separated and purified by the method of short-term exposure combining with differential sticking wall. Astrocyte was identified by glial fibers acidic protein (GFAP) selecting cell immunochemical staining. A mechanical-chemical damage (MCD) model was established via the primary spinal astrocytes of rats, and treatment was administered with different concentrations of muscone. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) was detected at 6, 12, 24, 48 and 72 h. SOD, MDA, LDH, TNF-alpha and intracellular calcium was detected at 3, 6 and 12 h. Glu in supernatant was detected respectively at 3, 6 and 12 h by enzyme-linked immunosorbent assay (ELISA) method. Intracellular calcium was detected respectively at 3, 6 and 12 h by flow cytometry method. MRNA expression of excitatory amino acid transporters (EAATs) and GFAP were detected by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method and protein expression of those by western blot at 6 h. Results Muscone reduced the levels of LDH, TNF-α, and MDA after injury, and upregulated the level of SOD. Muscone also reduced the density of extracellular Glu and suppressed the intracellular calcium level. Additionally, it decreased the expression levels of EAATs and GFAPs. Conclusions Muscone has a protective effect on astrocytes in a MCD and inhibits astrocytes’ proliferation.

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