scholarly journals DOK3 is involved in microglial cell activation in neuropathic pain by interacting with GPR84

Aging ◽  
2020 ◽  
Author(s):  
Wen-Shuang Gao ◽  
Yu-Juan Qu ◽  
Juan Huai ◽  
Hui Wei ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cell Activation ◽  
Microglial Cell

scholarly journals Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Katarzyna Popiolek-Barczyk ◽  
Anna Piotrowska ◽  
Wioletta Makuch ◽  
Joanna Mika
Keyword(s):  
Neuropathic Pain ◽  
Opioid Receptor ◽  
Pain Therapy ◽  
Cell Activation ◽  
Microglial Cell ◽  
Preclinical Model ◽  
No Production ◽  
Dependent Manner ◽  
Analgesic Effects ◽  
Primary Microglial Cell

Neuropathic pain is relatively less responsive to opioids than other types of pain, which is possibly due to a disrupted opioid system partially caused by the profound microglial cell activation that underlines neuroinflammation. We demonstrated that intrathecally injected biphalin, a dimeric enkephalin analog, diminished symptoms of neuropathy in a preclinical model of neuropathic pain in rats (CCI, chronic constriction injury of the sciatic nerve) at day 12 postinjury. Using primary microglial cell cultures, we revealed that biphalin did not influence cell viability but diminished NO production and expression of Iba1 in LPS-stimulated cells. Biphalin also diminished MOP receptor level, as well as pronociceptive mediators (iNOS, IL-1β, and IL-18) in an opioid receptor-dependent manner, and it was correlated with diminished p-NF-κB, p-IκB, p-p38MAPK, and TRIF levels. Biphalin reduced IL-6, IL-10, TNFα, p-STAT3, and p-ERK1/2 and upregulated SOCS3, TLR4, and MyD88; however, this effect was not reversed by naloxone pretreatment. Our study provides evidence that biphalin diminishes neuropathy symptoms, which might be partially related to reduced pronociceptive mediators released by activated microglia. Biphalin may be a putative drug for future pain therapy, especially for the treatment of neuropathic pain, when the lower analgesic effects of morphine are correlated with profound microglial cell activation.

scholarly journals Minocycline Enhances the Effectiveness of Nociceptin/Orphanin FQ during Neuropathic Pain

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Katarzyna Popiolek-Barczyk ◽  
Ewelina Rojewska ◽  
Agnieszka M. Jurga ◽  
Wioletta Makuch ◽  
Ferenz Zador ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cell Activation ◽  
Microglial Cell ◽  
Lumbar Spinal Cord ◽  
Orphanin Fq ◽  
Binding Assays ◽  
Analgesic Effects ◽  
Primary Microglial Cell ◽  
Lumbar Spinal

Nociceptin/orphanin FQ (N/OFQ) antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP), was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p.), a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.). Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Ourin vitrostudy showed that minocycline reducedNOPmRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain.

Neuroinflammation as a possible link between cannabinoids and addiction

2013 ◽  
Vol 26 (6) ◽  
pp. 334-346 ◽  
Author(s):  
Livia C.M. Rodrigues ◽  
Pedro H. Gobira ◽  
Antonio Carlos de Oliveira ◽  
Renan Pelição ◽  
Antonio Lucio Teixeira ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Microglial Activation ◽  
Cell Activation ◽  
Microglial Cell ◽  
Substance Dependence ◽  
Present Review ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
The Past

ObjectiveSubstance dependence disorder is a chronically relapsing condition characterised by neurobiological changes leading to loss of control in restricting a substance intake, compulsion and withdrawal syndrome. In the past few years, (endo)cannabinoids have been raised as a possible target in the aetiology of drug addiction. On the other hand, although the exact mechanisms of the genesis of addiction remain poorly understood, it is possible that neuroinflammation might also play a role in the pathophysiology of this condition. Studies demonstrated that (endo)cannabinoids act as immunomodulators by inhibiting cytokines production and microglial cell activation. Thus, in the present review, we explore the possible role of neuroinflammation on the therapeutic effects of cannabinoids on drug addiction.MethodsWe conducted an evidence-based review of the literature in order to assess the role of cannabinoids on the neuroinflammatory hypothesis of addiction (terms: addiction, cannabinoids and inflammation). We searched PubMed and BioMedCentral databases up to April 2014 with no date restrictions.ResultsIn all, 165 eligible articles were included in the present review. Existing evidence suggests that disruption in cannabinoid signalling during the drug addiction process leads to microglial activation and neuroinflammation.ConclusionThe literature showed that inflammation and changes in endocannabinod signalling occur in drug abuse; however, it remains uncertain whether these changes are causally or coincidentally associated with addiction. Additional studies, therefore, are needed to elucidate the contribution of neuroinflammation on the behavioural and neuroprotective effects of cannabinoids on drug addiction.

scholarly journals Hormone regulation of microglial cell activation: relevance to multiple sclerosis

2005 ◽  
Vol 48 (2) ◽  
pp. 322-327 ◽  
Author(s):  
Paul D. Drew ◽  
Paul D. Storer ◽  
Jihong Xu ◽  
Janet A. Chavis
Keyword(s):  
Multiple Sclerosis ◽  
Cell Activation ◽  
Microglial Cell ◽  
Hormone Regulation

scholarly journals Signaling of Macrophage Inflammatory Protein (MIP)-3β Facilitates Dengue Virus-Induced Microglial Cell Migration

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 690
Author(s):  
Ming-Kai Jhan ◽  
Ting-Jing Shen ◽  
Po-Chun Tseng ◽  
Yung-Ting Wang ◽  
Chiou-Feng Lin
Keyword(s):  
Cell Migration ◽  
Dengue Virus ◽  
Viral Entry ◽  
Cell Activation ◽  
Microglial Cell ◽  
Inflammatory Protein ◽  
Infected Cells ◽  
Chemotactic Factors ◽  
And Migration ◽  
Macrophage Inflammatory Protein

The infection by dengue virus (DENV) of microglia causes cell activation and migration via a mechanism involving viral entry, RNA release, and Toll-like receptor 3 signaling. In this study, we demonstrated that secreted chemotactic factors present in microglial conditioned medium (MCM) facilitated cell motility in the murine BV2 microglial cells. The pharmacological disruption of lipid rafts/caveolae reduced DENV- and ultraviolet (UV)-inactivated MCM-induced microglial cell migration. An antibody-based cytokine/chemokine array showed an increase in macrophage inflammatory protein (MIP)-3β in MCM produced using DENV-infected cells. The pharmacological inhibition of c-Jun N-terminal kinase (JNK) retarded UV-MCM-induced microglial cell migration. These results demonstrate that secreted MIP-3β and its effect on the JNK signaling pathways mediates DENV-induced BV2 microglial cell migration.

c-Src function is necessary and sufficient for triggering microglial cell activation

Glia ◽  
2014 ◽  
Vol 63 (3) ◽  
pp. 497-511 ◽  
Author(s):  
Renato Socodato ◽  
Camila C. Portugal ◽  
Ivan Domith ◽  
Nádia A. Oliveira ◽  
Vivian S. M. Coreixas ◽  
...  
Keyword(s):  
Cell Activation ◽  
Microglial Cell ◽  
Necessary And Sufficient

Pain neurophysiology

2013 ◽  
Author(s):  
Hans-Georg Schaible ◽  
Rainer H. Straub
Keyword(s):  
Neuropathic Pain ◽  
Central Sensitization ◽  
Cell Activation ◽  
Warning Signal ◽  
Nociceptive Pain ◽  
Neural Function ◽  
Peripheral Sensitization ◽  
Nerve Fibres ◽  
Glial Cell Activation ◽  
Ectopic Discharges

Physiological pain is evoked by intense (noxious) stimuli acting on healthy tissue functioning as a warning signal to avoid damage of the tissue. In contrast, pathophysiological pain is present in the course of disease, and it is often elicited by low-intensity stimulation or occurs even as resting pain. Causes of pathophysiological pain are either inflammation or injury causing pathophysiological nociceptive pain or damage to nerve cells evoking neuropathic pain. The major peripheral neuronal mechanism of pathophysiological nociceptive pain is the sensitization of peripheral nociceptors for mechanical, thermal and chemical stimuli; the major peripheral mechanism of neuropathic pain is the generation of ectopic discharges in injured nerve fibres. These phenomena are created by changes of ion channels in the neurons, e.g. by the influence of inflammatory mediators or growth factors. Both peripheral sensitization and ectopic discharges can evoke the development of hyperexcitability of central nociceptive pathways, called central sensitization, which amplifies the nociceptive processing. Central sensitization is caused by changes of the synaptic processing, in which glial cell activation also plays an important role. Endogenous inhibitory neuronal systems may reduce pain but some types of pain are characterized by the loss of inhibitory neural function. In addition to their role in pain generation, nociceptive afferents and the spinal cord can further enhance the inflammatory process by the release of neuropeptides into the innervated tissue and by activation of sympathetic efferent fibres. However, in inflamed tissue the innervation is remodelled by repellent factors, in particular with a loss of sympathetic nerve fibres.

scholarly journals Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways

2020 ◽  
Vol 21 (12) ◽  
pp. 4319 ◽  
Author(s):  
Jihyun Park ◽  
Kyung Mi Jang ◽  
Kwan-Kyu Park
Keyword(s):  
Cell Activation ◽  
Microglial Cell ◽  
Vital Role ◽  
Sk Channels ◽  
Neuroinflammatory Response ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Light Chain Enhancer ◽  
Small Conductance

Neuroinflammation plays a vital role in neurodegenerative conditions. Microglia are a key component of the neuroinflammatory response. There is a growing interest in developing drugs to target microglia and thereby control neuroinflammatory processes. Apamin (APM) is a specifically selective antagonist of small conductance calcium-activated potassium (SK) channels. However, its effect on neuroinflammation is largely unknown. We examine the effects of APM on lipopolysaccharide (LPS)-stimulated BV2 and rat primary microglial cells. Regarding the molecular mechanism by which APM significantly inhibits proinflammatory cytokine production and microglial cell activation, we found that APM does so by reducing the expression of phosphorylated CaMKII and toll-like receptor (TLR4). In particular, APM potently suppressed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription (STAT)3 and phosphorylated mitogen-activated protein kinases (MAPK)-extracellular signal-regulated kinase (ERK). In addition, the correlation of NF-κB/STAT3 and MAPK-ERK in the neuroinflammatory response was verified through inhibitors. The literature and our findings suggest that APM is a promising candidate for an anti-neuroinflammatory agent and can potentially be used for the prevention and treatment of various neurological disorders.

scholarly journals Taming of macrophage and microglial cell activation by microRNA-124

Cell Research ◽  
2011 ◽  
Vol 21 (2) ◽  
pp. 213-216 ◽  
Author(s):  
Ashley T Conrad ◽  
Bonnie N Dittel
Keyword(s):  
Cell Activation ◽  
Microglial Cell ◽  
Microrna 124
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