Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord

2017 ◽  
Vol 55 (05) ◽  
pp. 453-464 ◽  
Author(s):  
Ming Liu ◽  
Qiu Hong Qiang ◽  
Qian Ling ◽  
Chang Xi Yu ◽  
Xuejun Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Proinflammatory Cytokines ◽  
Experimental Studies ◽  
Glial Activation ◽  
Pharmacological Significance

scholarly journals Intrathecal polymer-based interleukin-10 gene delivery for neuropathic pain

2006 ◽  
Vol 2 (4) ◽  
pp. 293-308 ◽  
Author(s):  
Erin D. Milligan ◽  
Ryan G. Soderquist ◽  
Stephanie M. Malone ◽  
John H. Mahoney ◽  
Travis S. Hughes ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Neuropathic Pain ◽  
Gene Delivery ◽  
Proinflammatory Cytokines ◽  
Interleukin 1 ◽  
Clinical Problem ◽  
Interleukin 10 ◽  
Synthetic Polymers ◽  
High Doses

AbstractResearch on communication between glia and neurons has increased in the past decade. The onset of neuropathic pain, a major clinical problem that is not resolved by available therapeutics, involves activation of spinal cord glia through the release of proinflammatory cytokines in acute animal models of neuropathic pain. Here, we demonstrate for the first time that the spinal action of the proinflammatory cytokine, interleukin 1 (IL-1) is involved in maintaining persistent (2 months) allodynia induced by chronic-constriction injury (CCI). The anti-inflammatory cytokine IL-10 can suppress proinflammatory cytokines and spinal cord glial amplification of pain. Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose required limits its potential clinical utility. Here we show that intrathecal gene therapy for neuropathic pain is improved sufficiently using two, distinct synthetic polymers, poly(lactic-co-glycolic) and polyethylenimine, that substantially lower doses of pDNA-IL-10 are effective. In conclusion, synthetic polymers used as i.t. gene-delivery systems are well-tolerated and improve the long-duration efficacy of pDNA-IL-10 gene therapy.

Ankle joint mobilization reduces axonotmesis-induced neuropathic pain and glial activation in the spinal cord and enhances nerve regeneration in rats

Pain ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 2653-2661 ◽  
Author(s):  
Daniel F. Martins ◽  
Leidiane Mazzardo-Martins ◽  
Vinícius M. Gadotti ◽  
Francisney P. Nascimento ◽  
Denise A.N. Lima ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Regeneration ◽  
Ankle Joint ◽  
Glial Activation ◽  
Joint Mobilization

scholarly journals Amorfrutins Relieve Neuropathic Pain through the PPARγ/CCL2 Axis in CCI Rats

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Pengfei Gao ◽  
Jiayu Wang ◽  
Zhen Su ◽  
Fayin Li ◽  
Xianlong Zhang
Keyword(s):  
Public Health ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Proinflammatory Cytokines ◽  
Public Health Problem ◽  
Elisa Assay ◽  
Concurrent Administration ◽  
Nociceptive Responses ◽  
New Treatment ◽  
Antagonist Gw9662

Neuropathic pain is a public health problem. Although many pharmaceuticals are used to treat neuropathic pain, effective and safe drugs do not yet exist. In this study, we tested nociceptive responses in CCI rats, and ELISA assay was performed to examine the expression of proinflammatory cytokines. We found that amorfrutins significantly reduce the pain behaviors in CCI rats and suppress the expression of proinflammatory cytokines (TNFα, IL-6, and IL-1β) and chemokines (CCL2/CCR2) in the spinal cord. However, concurrent administration of a PPARγ antagonist, GW9662, reversed the antihyperalgesic effect induced by amorfrutins. The results indicate that amorfrutins inhibit the inflammation and chemokine expression by activating PPARγ, thus relieving neuropathic pain in CCI rats. Therefore, PPARγ-CCL2/CCR2 pathway might represent a new treatment option for neuropathic pain.

scholarly journals Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Young S. Gwak ◽  
Claire E. Hulsebosch ◽  
Joong Woo Leem
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Glial Cells ◽  
Intracellular Signaling ◽  
Glial Activation ◽  
Chronic Neuropathic Pain ◽  
Pain Transmission ◽  
Cord Injury

The hyperactive state of sensory neurons in the spinal cord enhances pain transmission. Spinal glial cells have also been implicated in enhanced excitability of spinal dorsal horn neurons, resulting in pain amplification and distortions. Traumatic injuries of the neural system such as spinal cord injury (SCI) induce neuronal hyperactivity and glial activation, causing maladaptive synaptic plasticity in the spinal cord. Recent studies demonstrate that SCI causes persistent glial activation with concomitant neuronal hyperactivity, thus providing the substrate for central neuropathic pain. Hyperactive sensory neurons and activated glial cells increase intracellular and extracellular glutamate, neuropeptides, adenosine triphosphates, proinflammatory cytokines, and reactive oxygen species concentrations, all of which enhance pain transmission. In addition, hyperactive sensory neurons and glial cells overexpress receptors and ion channels that maintain this enhanced pain transmission. Therefore, post-SCI neuronal-glial interactions create maladaptive synaptic circuits and activate intracellular signaling events that permanently contribute to enhanced neuropathic pain. In this review, we describe how hyperactivity of sensory neurons contributes to the maintenance of chronic neuropathic pain via neuronal-glial interactions following SCI.

scholarly journals STING/NF-κB/IL-6-mediated inflammation in microglia contributes to spared nerve injury (SNI)-induced neuropathic pain

2021 ◽  
Author(s):  
Jia Sun ◽  
Ya-Qun Zhou ◽  
Bing-Yang Xu ◽  
Jia-Yan Li ◽  
Long-Qing Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Dorsal Horn ◽  
Proinflammatory Cytokines ◽  
Spinal Cord Dorsal Horn ◽  
Spared Nerve Injury ◽  
Downstream Effectors ◽  
Spinal Cord Dorsal ◽  
Underlying Mechanisms

Abstract Background Innate immune response acts as a first line of host defense against damage and are initiated following the recognition of pathogen-associated molecular patterns (PAMPs). For double-stranded DNA (dsDNA) sensing, interferon gene stimulator (STING) was discovered to be an integral sensor, and could mediate the immune and inflammatory response. However, it is unclear the underlying mechanisms of STING in the development of neuropathic pain. Methods Neuropathic pain model was established by spared nerve injury (SNI). STING agonist DMXAA was introduced into BV-2 cells to assess the inflammatory response in microglia cells. Selective STING antagonist C-176 were administered in the early and late stage following SNI and the mechanical sensitivity and thermal responsiveness were assessed using Von Frey filaments and hot plate tests separately. To investigate the underlying mechanisms, recombinant IL-6 was injected intrathecally and its downstream effectors were examined. The level of dsDNA in the peripheral blood following SNI was assessed using Elisa analysis. STING signaling pathway and its downstream effectors were assessed by qPCR, western blots, Elisa and immunofluorescence staining. Meanwhile, microglia activation and proinflammatory cytokines expression were also assessed in the spinal cord. Results We found dsDNA was significantly increased and STING signaling pathway was activated in dorsal horn microglia following SNI, and our study using BV-2 cells showed that DMXAA significantly activated STING/TANK-binding kinase 1 (TBK1)/nuclear factor-kappa B (NF-κB) pathway, and increased the production of proinflammatory cytokines, as well as phosphorylated the Janus-activated kinase 2/signal transducer activator of transcription 3 (JAK2/STAT3) signal in microglia. Early but not late intrathecal injection of C-176 attenuated SNI-induced pain hypersensitivity, microglia activation, proinflammatory factors and phosphorylated JAK2/STAT3 in the spinal cord dorsal horn. Last, the analgesic effect of C-176 were greatly abolished by recombinant IL-6 following SNI. Conclusions We provided evidence clarifying dsDNA mediated activation of microglial STING signaling pathway, after which promoting expression of proinflammatory cytokines that are required for central sensitization in the spinal cord dorsal horn of SNI model. Further analysis showed that microglial STING/TBK1/NF-κB may contribute to hyperalgesia initiation via IL-6/JAK2/STAT3 signaling. Pharmacological blockade of STING may be a promising target during the initiation of neuropathic pain.

SOCS1 regulates neuropathic pain by inhibiting neuronal sensitization and glial activation in mouse spinal cord

2016 ◽  
Vol 124 ◽  
pp. 231-237 ◽  
Author(s):  
Ting Zhang ◽  
Kai Sun ◽  
Wen Shen ◽  
Le Qi ◽  
Wei Yin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Glial Activation ◽  
Mouse Spinal Cord

scholarly journals Fatty acid suppression of glial activation prevents central neuropathic pain after spinal cord injury

Pain ◽  
2019 ◽  
Vol 160 (12) ◽  
pp. 2724-2742 ◽  
Author(s):  
Marieta Georgieva ◽  
Yuting Wei ◽  
Maria Dumitrascuta ◽  
Roger Pertwee ◽  
Nanna B. Finnerup ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Fatty Acid ◽  
Glial Activation ◽  
Acid Suppression ◽  
Central Neuropathic Pain ◽  
Cord Injury
Sign in / Sign up

Export Citation Format

Share Document