Suberoylanilide Hydroxamic Acid Ameliorates Pain Sensitization in Central Neuropathic Pain After Spinal Cord Injury via the HDAC5/NEDD4/SCN9A Axis

Wang, Changsheng; Chen, Rongsheng; Zhu, Xitian; Zhang, Xiaobo

doi:10.1007/s11064-023-03913-z

Cited by 4 publications

(12 citation statements)

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“…48 A recent study conducted in SCI-induced neuropathic pain mice revealed that treatment with an HDAC inhibitor suppressed the expression of HDAC5 and Nav1.7 in DRG neurons, while increasing NEDD4 expression. 26 They demonstrated that knockdown of HDAC5 upregulated NEDD4 levels by promoting the enrichment of H3K27Ac in the NEDD4 promoter, which subsequently augmented the ubiquitination of Nav1.7 and led to a reduction in Nav1.7 expression in DRG. 26 On the contrary, Matsushita et al demonstrated that sustained downregulation of Nav1.8 in DRG neurons in pSNLinduced neuropathic pain rats, attributed to the transcriptional repression facilitated by HDAC.…”

Section: Drg Neuronsmentioning

confidence: 99%

“…26 They demonstrated that knockdown of HDAC5 upregulated NEDD4 levels by promoting the enrichment of H3K27Ac in the NEDD4 promoter, which subsequently augmented the ubiquitination of Nav1.7 and led to a reduction in Nav1.7 expression in DRG. 26 On the contrary, Matsushita et al demonstrated that sustained downregulation of Nav1.8 in DRG neurons in pSNLinduced neuropathic pain rats, attributed to the transcriptional repression facilitated by HDAC. 50 Neuron-restrictive silencer factor (NRSF) is an epigenetic silencing effector, binding to the neuronrestrictive silencing elements (NRSE) within the promoter region of genes, such as Nav1.8, Kv4.3 and μ-opioid receptor genes.…”

Section: Drg Neuronsmentioning

confidence: 99%

“…25 Moreover, in a mouse model of central neuropathic pain induced by spinal cord injury (SCI), Wang et al found a significant increase in the expression of HDAC1 in DRG. 26 Nevertheless, its specific cellular distribution within the DRG remains unclear. In the spinal nerve ligation (SNL)-induced neuropathic pain model, a series of experiments showed an increase in HDAC1 expression on the ipsilateral of the spinal dorsal horn.…”

Section: Class I Hadcsmentioning

confidence: 99%

“…Moreover, the level of HDAC5 was found to be remarkably increased in the DRG of SCI mice. 26 In a mouse model of partial sciatic nerve ligation (pSNL)-induced neuropathic pain, Gu et al observed an elevation of HDAC5 in neurons, microglia, and astrocytes of the spinal dorsal horn. 37…”

Section: Class II Hadcsmentioning

confidence: 99%

“…An increasing body of evidence has verified the analgesia effects of SAHA in neuropathic pain states. 26,50,107,108 For example, Feng et al found that daily intrathecal injection (i.t.) of SAHA (100 nmol/day or 200 nmol/day) reversed the mechanical allodynia in SNL-induced neuropathic pain rats.…”

Section: Sahamentioning

confidence: 99%

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Histone deacetylase as emerging pharmacological therapeutic target for neuropathic pain: From epigenetic to selective drugs

Zhang,

Jiao,

et al. 2024

CNS Neurosci Ther

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BackgroundNeuropathic pain remains a formidable challenge for modern medicine. The first‐line pharmacological therapies exhibit limited efficacy and unfavorable side effect profiles, highlighting an unmet need for effective therapeutic medications. The past decades have witnessed an explosion in efforts to translate epigenetic concepts into pain therapy and shed light on epigenetics as a promising avenue for pain research. Recently, the aberrant activity of histone deacetylase (HDAC) has emerged as a key mechanism contributing to the development and maintenance of neuropathic pain.AimsIn this review, we highlight the distinctive role of specific HDAC subtypes in a cell‐specific manner in pain nociception, and outline the recent experimental evidence supporting the therapeutic potential of HDACi in neuropathic pain.MethodsWe have summarized studies of HDAC in neuropathic pain in Pubmed.ResultsHDACs, widely distributed in the neuronal and non‐neuronal cells of the dorsal root ganglion and spinal cord, regulate gene expression by deacetylation of histone or non‐histone proteins and involving in increased neuronal excitability and neuroinflammation, thus promoting peripheral and central sensitization. Importantly, pharmacological manipulation of aberrant acetylation using HDAC‐targeted inhibitors (HDACi) has shown promising pain‐relieving properties in various preclinical models of neuropathic pain. Yet, many of which exhibit low‐specificity that may induce off‐target toxicities, underscoring the necessity for the development of isoform‐selective HDACi in pain management.ConclusionsAbnormally elevated HDACs promote neuronal excitability and neuroinflammation by epigenetically modulating pivotal gene expression in neuronal and immune cells, contributing to peripheral and central sensitization in the progression of neuropathic pain, and HDACi showed significant efficacy and great potential for alleviating neuropathic pain.

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Section: Drg Neuronsmentioning

confidence: 99%