5-Hydroxymethylcytosine (5hmC) and Ten-eleven translocation 1–3 (TET1–3) proteins in the dorsal root ganglia of mouse: Expression and dynamic regulation in neuropathic pain

Chamessian, Alexander; Qadri, Yawar J.; Cummins, Matthew; Hendrickson, Michele; Berta, Temugin; Buchheit, Thomas Edward; Ven, Thomas Van de

doi:10.1080/08990220.2017.1292237

Cited by 12 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent work suggests the involvement of TET1 in pathological pain. TET1 is expressed exclusively in the neurons of the DRG and spinal cord dorsal horn [34,35], 2 major pain-related regions in the nervous system. Peripheral SNL and paw injection of formalin or complete Freund's adjuvant (CFA) increased TET1 expression in ipsilateral spinal cord dorsal horn, but not in the DRG [14,[34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

“…TET1 is expressed exclusively in the neurons of the DRG and spinal cord dorsal horn [34,35], 2 major pain-related regions in the nervous system. Peripheral SNL and paw injection of formalin or complete Freund's adjuvant (CFA) increased TET1 expression in ipsilateral spinal cord dorsal horn, but not in the DRG [14,[34][35][36][37][38]. Knockdown of spinal TET1 alleviated the formalin-, CFA-, and SNL-induced nociceptive behaviors through blocking TET1-triggered expression of dorsal horn miR-365, Stat3, and BDNF, respectively [35,37,38].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

Qiang

Wei

et al. 2019

Neurotherapeutics

View full text Add to dashboard Cite

Peripheral nerve injury downregulates the expression of the μ-opioid receptor (MOR) and voltage-gated potassium channel subunit Kv1.2 by increasing their DNA methylation in the dorsal root ganglion (DRG). Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) causes DNA demethylation. Given that DRG MOR and Kv1.2 downregulation contribute to neuropathic pain genesis, this study investigated the effect of DRG TET1 overexpression on neuropathic pain. Overexpression of TET1 in the DRG through microinjection of herpes simplex virus expressing full-length TET1 mRNA into the injured rat DRG significantly alleviated the fifth lumbar spinal nerve ligation (SNL)-induced pain hypersensitivities during the development and maintenance periods, without altering acute pain or locomotor function. This microinjection also restored morphine analgesia and attenuated morphine analgesic tolerance development after SNL. Mechanistically, TET1 microinjection rescued the expression of MOR and Kv1.2 by reducing the level of 5-methylcytosine and increasing the level of 5-hydroxymethylcytosine in the promoter and 5′ untranslated regions of the Oprml1 gene (encoding MOR) and in the promoter region of the Kcna2 gene (encoding Kv1.2) in the DRG ipsilateral to SNL. These findings suggest that DRG TET1 overexpression mitigated neuropathic pain likely through rescue of MOR and Kv1.2 expression in the ipsilateral DRG. Virus-mediated DRG delivery of TET1 may open a new avenue for neuropathic pain management.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

Qiang

Wei

et al. 2019

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…The opposite process is DNA demethylation generates 5-hydroxymethylcytosine (5hmC) through the oxidation of 5 mC by TET1-3 [ 35 ]. Literature has shown that TET1-3 is expressed in DRG of both naïve and nerve injury modeling mice [ 36 ]. SNL downregulated the expression of the μ-opioid receptor (MOR) and voltage-gated potassium channel subunit Kv1.2 by increasing their DNA methylation through TET1 in the DRG.…”

Section: Dna/rna Methylation and Chronic Painmentioning

confidence: 99%

The Epigenetic Mechanisms Involved in Chronic Pain in Rodents: A Mini- Review

Liu

Xin

2022

View full text Add to dashboard Cite

: Chronic pain, as a common distressing neurological disorder, about 30% of the global population suffers from it. In addition to being highly prevalent, chronic pain causes heavy economic and social burden. Although substantial progress has been achieved to dissect the underlying mechanism of chronic pain in the past few decades, the incidence and treatment of this neurological illness is yet not properly managed in clinical practice. While nerve injury-, chemotherapy- or inflammation-induced functional regulation of gene expression in the dorsal root ganglion and spinal cord are extensively reported to be involved in the pathogenic process of chronic pain, the specific mechanism of these altered transcriptional profile still remains unclear. Recent studies have shown that epigenetic mechanisms, including DNA/RNA methylation, histone modification and circular RNAs regulation, are involved in the occurrence and development of chronic pain. In this review, we provide a description of research on the role of epigenetic mechanism in chronic pain, summarize the latest clinical and preclinical advance in this field, and propose the potential directions for further research to elucidate the molecular mechanism underlying the pathogenesis of chronic pain.

show abstract

“…TET3 was suggested to be the main driving factor for the upregulation of 5hmC in the DRG after nerve injury ( 82 ). Wu et al ( 83 ) further showed that SNL surgery could trigger methylation of Oprml1 and Kcna2 , thereby increasing the amounts of 5mC with a corresponding decrease in the level of 5hmC, thus reducing the corresponding MOR and Kv1.2 protein levels and ultimately causing pain.…”

Section: Dna Demethylationmentioning

confidence: 99%

DNA Methylation: A Target in Neuropathic Pain

Jiang

Tan

et al. 2022

Front. Med.

View full text Add to dashboard Cite

Neuropathic pain (NP), caused by an injury or a disease affecting the somatosensory nervous system of the central and peripheral nervous systems, has become a global health concern. Recent studies have demonstrated that epigenetic mechanisms are among those that underlie NP; thus, elucidating the molecular mechanism of DNA methylation is crucial to discovering new therapeutic methods for NP. In this review, we first briefly discuss DNA methylation, demethylation, and the associated key enzymes, such as methylases and demethylases. We then discuss the relationship between NP and DNA methylation, focusing on DNA methyltransferases including methyl-CpG-binding domain (MBD) family proteins and ten-eleven translocation (TET) enzymes. Based on experimental results of neuralgia in animal models, the mechanism of DNA methylation-related neuralgia is summarized, and useful targets for early drug intervention in NP are discussed.

show abstract

5-Hydroxymethylcytosine (5hmC) and Ten-eleven translocation 1–3 (TET1–3) proteins in the dorsal root ganglia of mouse: Expression and dynamic regulation in neuropathic pain

Cited by 12 publications

References 28 publications

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

The Epigenetic Mechanisms Involved in Chronic Pain in Rodents: A Mini- Review

DNA Methylation: A Target in Neuropathic Pain

Contact Info

Product

Resources

About