Contribution of macrophages to peripheral neuropathic pain pathogenesis

Ristoiu, Violeta

doi:10.1016/j.lfs.2013.10.005

Cited by 60 publications

(53 citation statements)

References 110 publications

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“…5c) when compared to the control mice [21]. More specifically in the sensory signaling transduction, macrophages play a crucial role in the development of peripheral nerve injury-induced neuropathic pain and in the repair of sensory function [95]. It has been shown that the infiltration of macrophages into injured nerves is delayed in slow Wallerian degeneration mouse (Wld s ), which is accompanied by the impairment of thermal hyperalgesia development [77,115] and peripheral nerve regeneration [83].…”

Section: Role Of Macrophages In Peripheral Nerve Regenerationmentioning

confidence: 99%

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

2015

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The peripheral nervous system (PNS) has remarkable regenerative abilities after injury. Successful PNS regeneration relies on both injured axons and non-neuronal cells, including Schwann cells and immune cells. Macrophages are the most notable immune cells that play key roles in PNS injury and repair. Upon peripheral nerve injury, a large number of macrophages are accumulated at the injury sites, where they not only contribute to Wallerian degeneration, but also are educated by the local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus contributing to axonal regeneration. Significant progress has been made in understanding how macrophages are educated and polarized in the injured microenvironment as well as how they contribute to axonal regeneration. Following the discussion on the main properties of macrophages and their phenotypes, in this review, we will summarize the current knowledge regarding the mechanisms of macrophage infiltration after PNS injury. Moreover, we will discuss the recent findings elucidating how macrophages are polarized to M2 phenotype in the injured PNS microenvironment, as well as the role and underlying mechanisms of macrophages in peripheral nerve injury, Wallerian degeneration and regeneration. Furthermore, we will highlight the potential application by targeting macrophages in treating peripheral nerve injury and peripheral neuropathies.

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Section: Role Of Macrophages In Peripheral Nerve Regenerationmentioning

confidence: 99%

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

2015

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“…Furthermore, neuropathic pain pathogenesis depends on both changes in the activity of neuronal systems as well as microglia activation [3]. During the pathogenesis of neuropathic pain, resident microglia become activated [4], exhibiting up-regulation of the expression of cell surface receptors (including purinergic receptors and CD11b) [5,6], enhanced migratory ability [7] and pro-inflammatory cytokine release (including tumor necrosis factor (TNF)-α and brain-derived neurotropic factor (BDNF)) [8,9], which can enhance synaptic transmission. Together, these changes can accelerate the development of neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Positive Feedback Loop of Autocrine BDNF from Microglia Causes Prolonged Microglia Activation

Zhang¹,

Zeng²,

Yu³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. Methods: Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. Results: In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. Conclusion: Therefore, we suggest that microglial activation increases the synthesis of BDNF and that the release of BDNF can, in turn, activate microglia. A positive autocrine BDNF feedback loop from microglia may contribute to prolonged microglial activation.

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“…It was also shown that subdural electrical stimulation of the motor cortex induced antinociception in mice with central neuropathic pain in a thermal hyperalgesia model (RUSINA et al, 2005). Recently, it was also observed that subdural stimulation inhibits thermal hyperalgesia induced by persistent peripheral neuropathy in rats (VACULIN et al, 2008).…”

Section: Pain and Cortical Stimulationmentioning

confidence: 98%

“…Centrally, the glia cells are formed by macroglia (astrocytes and oligodendrocytes) and microglia. Oligodendrocytes are the myelin forming cells of the peripheral nervous system (PNS), corresponding to 40% of glial cells (ZHANG; DE KONINCK, 2006;RISTOIU, 2013). About 50% of glial cells are astrocytes and only 5-10% microglia (ZHANG; DE KONINCK, 2006).…”

Section: Cortical Stimulation and Neuropathic Painmentioning

confidence: 99%

Cortical Stimulation and Neuropathic Pain

et al. 2015

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Estimulação cortical e a dor neuropática. O presente trabalho é uma revisão de dados isiológicos e comportamentais sobre a estimulação elétrica do córtex motor (ECM) e seu papel durante a dor neuropática persistente. A ECM tem sido amplamente utilizada na clínica médica como ferramenta para controle da dor que não respondem satisfatoriamente a nenhum tipo de analgesia convencional. Alguns importantes mecanismos envolvidos na modulação nociceptiva não foram, até o momento, esclarecidos. O objetivo deste estudo foi descrever os mecanismos envolvidos durante a dor neuropática e apresentar a eiciência da estimulação elétrica do córtex motor utilizada no tratamento desta doença. As vias ascendentes da dor são ativadas por receptores periféricos, onde há a transdução do estímulo químico, físico ou mecânico, em impulso nervoso, transmitindo este até a coluna posterior da medula espinal, onde ocorre conexão com neurônios de segunda ordem e ascendem à diferentes locais do sistema nervoso central, onde o estímulo periférico é percebido como dor. Por ser comprovada grande modulação deste sentido no córtex motor, vem sendo estudado o efeito da ECM para mimetizar os efeitos na pratica clinica e aperfeiçoar os tratamentos empregados durante a dor crônica. A ECM ganhou uma atenção especial nos últimos anos devido a sua ação em reverter quadros de dor neuropática de origem crônica, esta sendo mais eiciente do que a estimulação elétrica em diferentes locais e núcleos relacionados a dor. Palavras-chave: Córtex motor; Dor neuropática; Estimulação elétrica; Nocicepção AbstractThis paper is a review of physiological and behavioral data on motor cortex stimulation (MCS) and its role in persistent neuropathic pain. MCS has been widely used in clinical medicine as a tool for the management of pain that does not respond satisfactorily to any kind of conventional analgesia. Some important mechanisms involved in nociceptive modulation still remains unclear. The aim of this study was to describe the mechanisms involved in neuropathic pain and introduce the effectiveness of electrical stimulation of the motor cortex used there is the transduction of a chemical, physical or mechanical stimulus as a nerve impulse, where this impulse is transmitted to the dorsal horn of the spinal cord, which connects with second-order neurons and ascends to different locations in the central nervous system where the stimulus is perceived as pain. Because MCS has been proved to modulate this pathway in the motor cortex, it has been studied to mimic its effects in clinical practice and improve the treatments used for chronic pain. MCS has gained much attention in recent years due to its action in reversing chronic neuropathic pain, this being more effective than electrical stimulation at different locations and related pain nuclei.

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Contribution of macrophages to peripheral neuropathic pain pathogenesis

Cited by 60 publications

References 110 publications

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

Positive Feedback Loop of Autocrine BDNF from Microglia Causes Prolonged Microglia Activation

Cortical Stimulation and Neuropathic Pain

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