scholarly journals Gene therapy directed at the neuroimmune component of chronic pain with particular attention to the role of TNFα

2008 ◽  
Vol 437 (3) ◽  
pp. 209-213 ◽  
Author(s):  
Marina Mata ◽  
Shuanglin Hao ◽  
David J. Fink
Keyword(s):  
2007 ◽  
Author(s):  
Jeffrey I. Gold ◽  
Trina Haselrig ◽  
D. Colette Nicolaou ◽  
Katharine A. Belmont

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.


2020 ◽  
Vol 20 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Sonali Bhakta ◽  
Toshifumi Tsukahara

Editing mutated genes is a potential way for the treatment of genetic diseases. G-to-A mutations are common in mammals and can be treated by adenosine-to-inosine (A-to-I) editing, a type of substitutional RNA editing. The molecular mechanism of A-to-I editing involves the hydrolytic deamination of adenosine to an inosine base; this reaction is mediated by RNA-specific deaminases, adenosine deaminases acting on RNA (ADARs), family protein. Here, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.


Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.


2019 ◽  
Vol 712 ◽  
pp. 134483
Author(s):  
Morayo G. Adebiyi ◽  
Jeanne Manalo ◽  
Rodney E. Kellems ◽  
Yang Xia

2012 ◽  
Vol 2 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Gordon JG Asmundson ◽  
Holly A Parkerson ◽  
Mark Petter ◽  
Melanie Noel

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 278-279
Author(s):  
M Defaye ◽  
N Abdullah ◽  
M Iftinca ◽  
C Altier

Abstract Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown. Aims To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain. Methods We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation. Results Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation. Conclusions Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients. Funding Agencies CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship


2021 ◽  
Author(s):  
Hannah Waleed Haddad ◽  
Nikita Reddy Mallepalli ◽  
John Emerson Scheinuk ◽  
Pranav Bhargava ◽  
Elyse M. Cornett ◽  
...  

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