Regulation by noncoding RNAs of local translation, injury responses, and pain in the peripheral nervous system

Li, Xinbei; Jin, Daniel S.; Eadara, Sreenivas; Meffert, Mollie K.

doi:10.1016/j.ynpai.2023.100119

Cited by 2 publications

(2 citation statements)

References 243 publications

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“…The functional specificity of cortical networks and their projection targets in the pain process occurs at least on four interconnected levels: dynamic activity states within the cortical network; functionally distinct subdomains; specific circuit connections that distinguish pain from other functions; and co-active cell assemblies [6]. Among these, intercellular communication and molecular signaling pathways within specific circuit connections play a pivotal role in the sensitization and regulation of nociceptive pathways in the sensory nervous system and the pathological process of NPP [7,8,9,10].…”

Section: Introductionmentioning

confidence: 99%

Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain

Xiao,

Wang,

et al. 2024

Biomol Biomed

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Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as IL-1β and TNF-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.

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Section: Introductionmentioning

confidence: 99%

Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain

Xiao,

Wang,

et al. 2024

Biomol Biomed

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“…These changes lead to a persistent increase in pain-related synaptic transmission and maladaptive structural changes in the spinal dorsal horn, which is referred to as central sensitization, and is a critical event in the initiation and maintenance of neuropathic pain. − Compelling evidence has suggested that the establishment of peripheral and central sensitization following nerve injury depends on de novo protein synthesis . An increasing number of studies have revealed that nerve injury–induced changes in epitopes in the dorsal root ganglia (DRG) and dorsal horn require the translational regulation of protein. − …”

Section: Introductionmentioning

confidence: 99%

Neuralized1-Mediated CPEB3 Ubiquitination in the Spinal Dorsal Horn Contributes to the Pathogenesis of Neuropathic Pain in Rats

Zhang,

Gao

et al. 2023

ACS Chem. Neurosci.

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Compelling evidence has shown that Neuralized1 (Neurl1) facilitates hippocampal-dependent memory storage by modulating cytoplasmic polyadenylation element-binding protein 3 (CPEB3)-dependent protein synthesis. In the current study, we investigated the role of Neurl1 in the pathogenesis of neuropathic pain and the underlying mechanisms. The neuropathic pain was evaluated by lumbar 5 spinal nerve ligation (SNL) in rats. Immunofluorescence staining, Western blotting, qRT-PCR, and coimmunoprecipitation (Co-IP) were performed to investigate the underlying mechanisms. Our results showed that SNL led to an increase of Neurl1 in the spinal dorsal horn. Spinal microinjection of AAV-EGFP-Neurl1 shRNA alleviated mechanical allodynia; decreased the level of CPEB3 ubiquitination; inhibited the production of GluA1, GluA2, and PSD95; and reduced GluA1-containing AMPA receptors in the membrane of the dorsal horn following SNL. Knockdown of spinal CPEB3 decreased the production of GluA1, GluA2, and PSD95 in the dorsal horn and attenuated abnormal pain after SNL. Overexpression of Neurl1 in the dorsal horn resulted in pain-related hypersensitivity in naïve rats; raised the level of CPEB3 ubiquitination; increased the production of GluA1, GluA2, and PSD95; and augmented GluA1-containing AMPA receptors in the membrane in the dorsal horn. Moreover, spinal Neurl1 overexpression-induced mechanical allodynia in naïve rats was partially reversed by repeated intrathecal injections of CPEB3 siRNA. Collectively, our results suggest that SNL-induced upregulation of Neurl1 through CPEB3 ubiquitination-dependent production of GluA1, GluA2, and PSD95 in the dorsal horn contributes to the pathogenesis of neuropathic pain in rats. Targeting spinal Neurl1 might be a promising therapeutic strategy for the treatment of neuropathic pain.

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Regulation by noncoding RNAs of local translation, injury responses, and pain in the peripheral nervous system

Cited by 2 publications

References 243 publications

Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain

Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain

Neuralized1-Mediated CPEB3 Ubiquitination in the Spinal Dorsal Horn Contributes to the Pathogenesis of Neuropathic Pain in Rats

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