HSV-mediated transfer of interleukin-10 reduces inflammatory pain through modulation of membrane tumor necrosis factor α in spinal cord microglia

Zhou, Zhongxing; Peng, Xiangmin; Hao, Shuanglin; Fink, David J.; Mata, Marina

doi:10.1038/sj.gt.3303054

Cited by 86 publications

(89 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[21]. Inoculation of rats with a herpes simplex virus IL-10 vector, 10 days before intraplantar formalin administration, resulted in reduced pain sensitivity and decreased expression of TNF-␣ in the spinal cord [22]. Elevated levels of IL-10 have been suggested to be of pathophysiological significance in autoimmune and inflammatory diseases, such as lupus erythematosus [23], systemic sclerosis [24] and vesicular bullous diseases [25,26].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 levels in rat models of nerve damage and neuropathic pain

Khan

Ramadan

Korczeniewska

et al. 2015

Neuroscience Letters

View full text Add to dashboard Cite

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to play a role in inflammatory and autoimmune disorders as well as in neuropathic pain conditions. The objective of the present study was to assess the levels of IL-10 in rat's dorsal root ganglion (DRG) and the sciatic nerve following four different forms of sciatic nerve injury. The models used to induce the injury included two models of partial nerve injury: partial sciatic ligation (PSL) and chronic constriction injury (CCI), a model of complete sciatic transection (CST) and a model of perineural inflammation with minimal nerve damage (neuritis). Withdrawal responses for mechanical stimulus and withdrawal latency for thermal stimulation were used to measure mechanical and thermal hyperalgesia, respectively, and duration of the nociceptive withdrawal reflex to mechanical stimulus was used to measure mechanical hyperalgesia. The affected and contra-lateral nerves and the affected side DRG IL-10 levels were assessed by the means of enzyme-linked immunosorbent assay (ELISA), 3 and 8 days following the procedure and were compared to naïve rats' IL-10 levels. The rats exposed to CCI and neuritis developed significant mechanical and thermal hyperalgesia as well as mechanical hyperalgesia 3 and 8 days following the surgical procedure. Rats exposed to CST did not respond to mechanical stimulation and developed thermal hypoalgesia 3 and 8 days after the surgery. The DRG IL-10 levels were significantly reduced 3 and 8 days following CCI and PSL, significantly increased 3 and 8 days following CST, and remained unchanged following neuritis. The sciatic nerve IL-10 levels reduced significantly in both injured and contra-lateral nerves 3 and 8 days following CCI and PSL, elevated significantly in the injured but not in the contra-lateral nerve 3 and 8 days following CST and remained unchanged following neuritis. The results of this study suggest that IL-10's role in the neuropathic pain etiology may be specific to nerve injury type. Complete nerve transection increases while partial nerve injury reduces IL-10 levels in the involved nerve, and DRG. Perineural inflammation with minimal nerve damage has no effect on IL-10 levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Interleukin-10 levels in rat models of nerve damage and neuropathic pain

Khan

Ramadan

Korczeniewska

et al. 2015

Neuroscience Letters

View full text Add to dashboard Cite

show abstract

“…We have previously reported that nonreplicating HSV vectors similar to the one used in this study are effective in delivering transgenes to DRG in vivo (49,50), and the transgene product is released by the central afferent terminals of transduced DRG (51). We confirmed that subcutaneous inoculation of QHNgSR resulted in the production of NgSR in DRG neurons in vivo.…”

Section: Transfection Of Drg By Qhngsr Increases Regeneration Of Centmentioning

confidence: 99%

Soluble Nogo Receptor Down-regulates Expression of Neuronal Nogo-A to Enhance Axonal Regeneration

Peng

Zhou

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Nogo-A, a member of the reticulon family, is present in neurons and oligodendrocytes. Nogo-A in central nervous system (CNS) myelin prevents axonal regeneration through interaction with Nogo receptor 1, but the function of Nogo-A in neurons is less known. We found that after axonal injury, Nogo-A is increased in dorsal root ganglion (DRG) neurons unable to regenerate following a dorsal root injury or a sciatic nerve ligation-cut injury and that exposure in vitro to CNS myelin dramatically enhanced neuronal Nogo-A mRNA and protein through activation of RhoA while inhibiting neurite growth. Knocking down neuronal Nogo-A by small interfering RNA results in a marked increase of neurite outgrowth. We constructed a nonreplicating herpes simplex virus vector (QHNgSR) to express a truncated soluble fragment of Nogo receptor 1 (NgSR). NgSR released from QHNgSR prevented myelin inhibition of neurite extension by hippocampal and DRG neurons in vitro. NgSR prevents RhoA activation by myelin and decreases neuronal Nogo-A. Subcutaneous inoculation of QHNgSR to transduce DRG neurons resulted in improved regeneration of myelinated fibers in both the dorsal root and the spinal dorsal root entry zone, with concomitant improvement in sensory behavior. The results indicate that neuronal Nogo-A is an important intermediate in neurite growth dynamics and its expression is regulated by signals related to axonal injury and regeneration, that CNS myelin appears to activate signaling events that mimic axonal injury, and that NgSR released from QHNgSR may be used to improve recovery after injury.

show abstract

“…Expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, was reported to reduce pain-related behaviors in the rodent formalin model, an effect likely achieved via the reduction of proinflammatory factors (e.g., tumor necrosis factor [TNF]) in spinal microglia. 10 11 The neuropathic pain observed in trigeminal neuralgia can be modeled in rodents with the ligation of the infraorbital nerve, part of the maxillary division of the trigeminal system. The maxillary nerve is the branch carrying sensory information from the cheek area, or in rodents, the whisker pad.…”

Section: Clinical Trialsmentioning

confidence: 99%

Herpes Simplex Virus–Based Gene Therapies for Chronic Pain

Weiss

Boulis

2012

Journal of Pain & Palliative Care Pharmacotherapy

View full text Add to dashboard Cite

The promise of gene therapy in chronic pain management is described. Use of the Herpes simplex virus to deliver such therapy is discussed. Clinical trials of gene-based therapy for neuropathic, cancer, and inflammatory pain are summarized. The potential role for such therapies are discussed. This feature is adapted from paineurope 2012; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.Chronic pain continues to impair quality of life for millions of people, and therefore presents a serious ongoing challenge to clinicians and researchers. Current treatments (e.g., opioid analgesics) lack long-term efficacy and significant off-target effects often accompany their administration. Gene therapy is a promising alternative to traditional pharmacological treatments in targeting pain symptoms originating from multiple physiological mechanisms. The array of viral vectors now available can provide long-lasting transgene expression when appropriate.

show abstract

HSV-mediated transfer of interleukin-10 reduces inflammatory pain through modulation of membrane tumor necrosis factor α in spinal cord microglia

Cited by 86 publications

References 34 publications

Interleukin-10 levels in rat models of nerve damage and neuropathic pain

Interleukin-10 levels in rat models of nerve damage and neuropathic pain

Soluble Nogo Receptor Down-regulates Expression of Neuronal Nogo-A to Enhance Axonal Regeneration

Herpes Simplex Virus–Based Gene Therapies for Chronic Pain

Contact Info

Product

Resources

About