Small interfering RNA-mediated knockdown of NF-κBp65 attenuates neuropathic pain following peripheral nerve injury in rats

Sun, Tao; Luo, Jian-Gang; Jia, Mingrui; Li, Hui; Li, Kezhong; Fu, Zhijian

doi:10.1016/j.ejphar.2012.02.017

Cited by 50 publications

(46 citation statements)

References 54 publications

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“…Interestingly, NF-B is also activated in the spinal cord in response to peripheral nerve injury or tissue inflammation. In the rat chronic constriction injury (CCI) model, we previously observed extensive colocalization of NF-B/p65 with TNF␣ in the spinal dorsal horn (36), and down-regulation of spinal NF-B/ p65 expression significantly attenuated sciatic nerve ligation-induced mechanical and thermal hyperalgesia (19). In addition, spinal NF-B is also activated following injection of CFA or formalin into the footpad, and spinal application of an NF-B inhibitor reduces painrelated behavior (18,37,38).…”

Section: Discussionmentioning

confidence: 99%

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Activation of Spinal NF‐κB/p65 Contributes to Peripheral Inflammation and Hyperalgesia in Rat Adjuvant‐Induced Arthritis

Luo

Zhao

et al. 2014

Arthritis & Rheumatology

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Objective. It is known that noxious stimuli from inflamed tissue may increase the excitability of spinal dorsal horn neurons (a process known as central sensitization), which can signal back and contribute to peripheral inflammation. However, the underlying mechanisms have yet to be fully defined. A number of recent studies have indicated that spinal NF-B/p65 is involved in central sensitization, as well as pain-related behavior. Thus, the aim of this study was to determine whether NF-B/p65 can facilitate a peripheral inflammatory response in rat adjuvant-induced arthritis (AIA).Methods. Lentiviral vectors encoding short hairpin RNAs that target NF-B/p65 (LV-shNF-B/p65) were constructed for gene silencing. The spines of rats with AIA were injected with LV-shNF-B/p65 on day 3 or day 10 after treatment with Freund's complete adjuvant (CFA). During an observation period of 20 days, pain-related behavior, paw swelling, and joint histopathologic changes were evaluated. Moreover, the expression levels of spinal tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), and cyclooxygenase 2 (COX-2) were assessed on day 14 after CFA treatment. Conclusion. These findings indicate that spinal NF-B/p65 plays an important role in the initiation and development of both peripheral inflammation and hyperalgesia. Thus, inhibition of spinal NF-B/p65 expression may provide a potential treatment to manage painful inflammatory disorders. Results

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Section: Discussionmentioning

confidence: 99%

“…An additional scrambled sequence, 5Ј-TTCTCCGAACGTGTCACGT-3Ј, was designed as a negative control (NC). The lentiviral vectors LV-shNF-B/p65 and LV-NC were then generated in a manner as previously described (19). The final titer of recombinant virus was 5 ϫ 10 8 transducing units/ml.…”

Section: Methodsmentioning

confidence: 99%

Activation of Spinal NF‐κB/p65 Contributes to Peripheral Inflammation and Hyperalgesia in Rat Adjuvant‐Induced Arthritis

Luo

Zhao

et al. 2014

Arthritis & Rheumatology

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“…NF-jB expression and activation have been shown to be upregulated after sciatic nerve injury (Ma and Bisby, 1998), and it is known that NF-jB plays a major role in the expression of multiple pain-related mediators including several proinflammatory cytokines (Baeuerle and Henkel, 1994;Makarov, 2000). After intrathecal injection of lentiviral vectors, shRNA-mediated silencing of NF-jB attenuated the chronic constriction injury-induced expression of the proinflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) and additionally reduced mechanical allodynia and thermal hyperalgesia for > 4 weeks (Sun et al, 2012). Together these studies demonstrate that lentiviral vector-mediated knockdown of factors that contribute to central sensitization and persistent pain states is a viable strategy to alleviate and manage neuropathic pain.…”

Section: Lentiviral Vector-mediated Rna Silencing For In Vivo Models mentioning

confidence: 99%

“…Two other studies have used similar strategies to attenuate neuropathic pain by knocking down genes involved in the development of central sensitization (Zou et al, 2011;Sun et al, 2012). In these studies lentiviral vectors and shRNAs were used to knock down the expression of protein kinase C isoform-c (PKCc) or nuclear factor-jB (NF-jB).…”

Section: Lentiviral Vector-mediated Rna Silencing For In Vivo Models mentioning

confidence: 99%

“…First, they have been demonstrated to efficiently transduce postmitotic cells including CNS neurons in vitro and in vivo (Naldini et al, 1996a,b;Blomer et al, 1997;Thomas et al, 2003;Naldini, 2011) and have been effective in several animal models of CNS diseases (Ralph et al, 2005;Raoul et al, 2005;Singer et al, 2005;Sapru et al, 2006;Alves et al, 2008;Piedrahita et al, 2010;Horvath et al, 2011;Zou et al, 2011;Lv et al, 2012;Sun et al, 2012). Second, lentiviral vectors have been reported to have low cytotoxicity and immunogenicity (Naldini et al, 1996b;Abordo-Adesida et al, 2005;Schambach et al, 2013).…”

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Lentiviral Vector-Mediated RNA Silencing in the Central Nervous System

Hutson

Foster

Moon

et al. 2014

Human Gene Therapy Methods

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RNA silencing is an established method for investigating gene function and has attracted particular interest because of the potential for generating RNA-based therapeutics. Using lentiviral vectors as an efficient delivery system that offers stable, long-term expression in postmitotic cells further enhances the applicability of an RNAbased gene therapy for the CNS. In this review we provide an overview of both lentiviral vectors and RNA silencing along with design considerations for generating lentiviral vectors capable of RNA silencing. We go on to describe the current preclinical data regarding lentiviral vector-mediated RNA silencing for CNS disorders and discuss the concerns of side effects associated with lentiviral vectors and small interfering RNAs and how these might be mitigated.

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Lentiviral Vectors and Adeno‐Associated Virus Vectors: Useful Tools for Gene Transfer in Pain Research

Zheng

Wang

Bai

et al. 2018

The Anatomical Record

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Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research. In this review, we thoroughly outline the structure, category, advantages and disadvantages and the delivery methods of lentiviral and AAV vectors. The methods through which lentiviral and AAV vectors are delivered to targeted sites are closely related with the sites, level and period of transgene expression. Focus is placed on the various delivery methods applied to deliver vectors to spinal cord and dorsal root ganglion both of which play important roles in primary nociception. Our goal is to provide insight into the features of these two viral vectors and which administration approach can be chosen for different pain researches. Anat Rec,

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Small interfering RNA-mediated knockdown of NF-κBp65 attenuates neuropathic pain following peripheral nerve injury in rats

Cited by 50 publications

References 54 publications

Activation of Spinal NF‐κB/p65 Contributes to Peripheral Inflammation and Hyperalgesia in Rat Adjuvant‐Induced Arthritis

Activation of Spinal NF‐κB/p65 Contributes to Peripheral Inflammation and Hyperalgesia in Rat Adjuvant‐Induced Arthritis

Lentiviral Vector-Mediated RNA Silencing in the Central Nervous System

Lentiviral Vectors and Adeno‐Associated Virus Vectors: Useful Tools for Gene Transfer in Pain Research

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