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RE1-silencing transcription factor controls the acute-to-chronic neuropathic pain transition and Chrm2 receptor gene expression in primary sensory neurons Neurobiology
Neuropathic pain is associated with persistent changes in gene expression in primary sensory neurons, but the underlying epigenetic mechanisms that cause these changes remain unclear. The muscarinic cholinergic receptors (mAChRs), particularly the M2 subtype (encoded by the cholinergic receptor muscarinic 2 (Chrm2) gene), are critically involved in the regulation of spinal nociceptive transmission. However, little is known about how Chrm2 expression is transcriptionally regulated. Here we show that nerve injury persistently increased the expression of RE1-silencing transcription factor (REST, also known as neuron-restricti...
Source: Journal of Biological Chemistry - December 7, 2018 Category: Chemistry Authors: Jixiang Zhang, Shao-Rui Chen, Hong Chen, Hui-Lin Pan Tags: Molecular Bases of Disease Source Type: research

Identification of a signaling cascade that maintains constitutive {delta}-opioid receptor incompetence in peripheral sensory neurons Signal Transduction
μ-Opioid receptor (MOR) agonists are often used to treat severe pain but can result in adverse side effects. To circumvent systemic side effects, targeting peripheral opioid receptors is an attractive alternative treatment for severe pain. Activation of the δ-opioid receptor (DOR) produces similar analgesia with reduced side effects. However, until primed by inflammation, peripheral DOR is analgesically incompetent, raising interest in the mechanism. We recently identified a novel role for G-protein-coupled receptor kinase 2 (GRK2) that renders DOR analgesically incompetent at the plasma membrane. However, the mechanism ...
Source: Journal of Biological Chemistry - May 26, 2017 Category: Chemistry Authors: Allison Doyle Brackley, Shayda Sarrami, Ruben Gomez, Kristi A. Guerrero, Nathaniel A. Jeske Tags: Neurobiology Source Type: research

Opioid Receptor Expression in Neuropathic Pain Neurobiology
In this study, we determined the role of G9a in diminished MOR expression and opioid analgesic effects in animal models of neuropathic pain. We found that nerve injury in rats induced a long-lasting reduction in the expression level of MORs in the DRG but not in the spinal cord. Nerve injury consistently increased the enrichment of the G9a product histone 3 at lysine 9 dimethylation in the promoter of Oprm1 in the DRG. G9a inhibition or siRNA knockdown fully reversed MOR expression in the injured DRG and potentiated the morphine effect on pain hypersensitivity induced by nerve injury. In mice lacking Ehmt2 in DRG neurons, ...
Source: Journal of Biological Chemistry - April 14, 2016 Category: Chemistry Authors: Zhang, Y., Chen, S.-R., Laumet, G., Chen, H., Pan, H.-L. Tags: Molecular Bases of Disease Source Type: research

Epigenetic Control of Pannexin-1 Expression in Chronic Pain Neurobiology
In this study, we determined the epigenetic mechanism involved in increased Panx1 expression in the DRG after nerve injury. Spinal nerve ligation in rats significantly increased the mRNA and protein levels of Panx1 in the DRG but not in the spinal cord. Immunocytochemical labeling showed that Panx1 was primarily expressed in a subset of medium and large DRG neurons in control rats and that nerve injury markedly increased the number of Panx1-immunoreactive DRG neurons. Nerve injury significantly increased the enrichment of two activating histone marks (H3K4me2 and H3K9ac) and decreased the occupancy of two repressive histon...
Source: Journal of Biological Chemistry - June 4, 2015 Category: Chemistry Authors: Zhang, Y., Laumet, G., Chen, S.-R., Hittelman, W. N., Pan, H.-L. Tags: Molecular Bases of Disease Source Type: research

Identification of a Receptor for VGF Molecular Bases of Disease
VGF (nonacronymic) is a neuropeptide precursor that plays multiple roles in regulation of energy balance, reproduction, hippocampal synaptic plasticity, and pain. Data from a number of pain models showed significant up-regulation of VGF in sensory neurons. TLQP-21, one of the VGF-derived neuropeptides, has been shown to induce a hyperalgesic response when injected subcutaneously into the hind paw of mice. However, the precise role of VGF-derived neuropeptides in neuropathic pain and the molecular identity of the receptor for VGF-derived peptides are yet to be investigated. Here we identified gC1qR, the globular heads of th...
Source: Journal of Biological Chemistry - November 29, 2013 Category: Chemistry Authors: Chen, Y.–C., Pristera, A., Ayub, M., Swanwick, R. S., Karu, K., Hamada, Y., Rice, A. S. C., Okuse, K. Tags: Neurobiology Source Type: research