Activated Glia Increased the Level of Proinflammatory Cytokines in a Resiniferatoxin-Induced Neuropathic Pain Rat Model

Lei, Yishan; Sun, Yue; Lu, Cui’e; Ma, Zhengliang; Gu, Xiaoping

doi:10.1097/aap.0000000000000441

Cited by 23 publications

(27 citation statements)

References 22 publications

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“…includes activation of glia that induce a state of spinal neuroinflammation, which may reflect the persistent or altered primary sensory neuron input to the central nervous system that promotes the development of central neuroinflammation (Gwak et al, 2012, Ikeda et al, 2012, Trang et al, 2012, Chen et al, 2014, Lei et al, 2016, Liu et al, 2016. Therefore, both peripheral nerve injury and inflammation can upregulate the expression of glia, as marked by increased expression of CD11b or ionized calcium binding adaptor molecule 1 (Iba1) for microglia activation and Glial Fibrillary Acidic Protein (GFAP) for astrocyte activation, in both sensory ganglia…”

Section: Glia and Neuroinflammation The Transition From Acute To Chrmentioning

confidence: 99%

“…themselves and in the central nervous system (Ikeda et al, 2012, Romero et al, 2013, M'Dahoma et al, 2015, Liu et al, 2016, Lei et al, 2016. More importantly, pharmacological inhibition of glia has been shown to largely abolish enhanced neuronal excitation in models of chronic pain, suggesting that glial cells are the primary drivers of the neuronal hyperexcitability underpinning painful phenotypes (Ikeda et al, 2012).…”

Section: Glia and Neuroinflammation The Transition From Acute To Chrmentioning

confidence: 99%

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Central mechanisms of airway sensation and cough hypersensitivity

Driessen

McGovern

Narula

et al. 2017

Pulmonary Pharmacology & Therapeutics

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The airway sensory nervous system is composed of two anatomically distinct processing pathways that allow for the production of respiratory reflexes and voluntary evoked respiratory behaviours in response to sensing an airway irritation. Disordered sensory processing is a hallmark feature of many pulmonary disorders and results in the development of cough hypersensitivity syndrome, characterised by chronic cough and a persistent urge-to-cough in affected individuals. However, the mechanism underpinning how the airway sensory circuits become disordered, especially at the level of the central nervous system, is not well understood. In this mini-review we present well-defined mechanisms that lead to the development of chronic pain as a framework to explore the evidence that cough disorders may manifest due to neuroplasticity and sensitisation of important components of the airway sensory circuitry in the brain. We highlight recent discoveries of how airway sensory processing occurs in the brain in health and disease and additionally suggest areas where gaps exist in our current knowledge on the topic, with the goal of providing a better understanding of how airway circuits become dysfunctional in disease. This may in turn help identify novel therapeutic targets for restoring normal airway sensory processing and alleviating excessive cough.

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Section: Glia and Neuroinflammation The Transition From Acute To Chrmentioning

confidence: 99%

Section: Glia and Neuroinflammation The Transition From Acute To Chrmentioning

confidence: 99%

Central mechanisms of airway sensation and cough hypersensitivity

Driessen

McGovern

Narula

et al. 2017

Pulmonary Pharmacology & Therapeutics

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“…Spinal cord dorsal horn glial cell signal transduction-induced central sensitization is one of the important pathogeneses of DNPs. The activation of microglia produces and releases a variety of cytokines and excitatory substances of neurons or glial cells [ 2 – 4 ], promotes NR2B activation on neuronal cells, NR2B is a subunit on NMDA, and increases NMDA-mediated current. NMDA receptor activation can further induce the sensitization of the central nervous system, which is one of the important pathogeneses of DNP [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy

et al. 2019

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Purpose The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy. Methods In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors ( n = 8), while western blot ( n = 5) and an immunofluorescence double staining experiment ( n = 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons. Results The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro. Conclusions Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.

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“… 5 During periods of pain, reactive oxygen species (ROS) are released, which can damage the nerve and induce neuropathic pain. 6 , 7 ROS are also important factors in autophagy. 8 Although research has shown that cellular autophagy can lead to neurodegeneration or neuronal dysfunction, 9 the molecular mechanisms of neuropathic pain are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Effects of hyperbaric oxygen therapy on neuropathic pain via mitophagy in microglia

Han

Liu

et al. 2017

Mol Pain

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PurposeHyperbaric oxygen (HBO) therapy has been suggested to palliate neuropathic pain, but the mechanisms involved are not well understood. This study explored the involvement of microglial mitophagy via HBO relative to neuropathic pain therapy.Materials and methodsA total of 80 male Sprague Dawley rats were randomly divided into two groups: a normal group (n = 40) and a mitophagy inhibitor group (n = 40) in which the mitophagy inhibitor cyclosporin A (CsA) was administrated prior to chronic constriction injury (CCI). Groups (n = 10 rats per group) consisted of the following: control (C), sham operation (S), sciatic nerve with chronic constriction injury (CCI), and a CCI plus HBO treatment (CCI + HBO). Pain-related behaviors were evaluated using mechanical withdraw tendency and thermal withdraw latency analysis. Mitochondrial membrane potential was measured, and Western blot was employed to assess expression of NIX and BNIP3. Immunofluorescence changes in neuron protein (NESTIN) and mitochondria inner or outer layer proteins (TIM23, TOM20) were examined.ResultsHBO significantly ameliorated pain-related behaviors, which were downregulated by mitophagy inhibitors (P < 0.05). Mitochondrial membrane potential indexes were decreased after HBO therapy, but were reversed in the mitophagy inhibitor group (P < 0.05). HBO upregulated NIX and BNIP3 expression, which did not occur in the CCI group (P < 0.05). However, expression was reduced when mitophagy inhibitors were administered. Immunofluorescence examination showed that mitophagy in microglia was induced by CCI, which was upregulated after HBO treatment. This phenomenon was not observed in the mitophagy inhibitor group.ConclusionsHBO therapy palliated CCI-induced neuropathic pain in rats by upregulating microglial mitophagy. These results could serve as guidelines to improve neuropathic pain therapy using HBO to maximize therapeutic efficiency.

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Activated Glia Increased the Level of Proinflammatory Cytokines in a Resiniferatoxin-Induced Neuropathic Pain Rat Model

Abstract: Activated glia participate in the pathogenesis of RTX-induced neuropathic pain and are likely to be the source of proinflammatory cytokines. Inhibition of glia contributes to an analgesic effect. These findings provide a novel strategy for the treatment of postherpetic neuralgia.

Cited by 23 publications

References 22 publications

Central mechanisms of airway sensation and cough hypersensitivity

Central mechanisms of airway sensation and cough hypersensitivity

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy

Effects of hyperbaric oxygen therapy on neuropathic pain via mitophagy in microglia

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