Abstract：
:Opioid therapies for chronic pain are undermined by many adverse side effects that reduce their efficacy and lead to dependence, abuse, reduced quality of life, and even death. We have recently reported that sphingosine-1-phosphate (S1P) 1 receptor (S1PR1) antagonists block the development of morphine-induced hyperalgesia and analgesic tolerance. However, the impact of S1PR1 antagonists on other undesirable side effects of opioids, such as opioid-induced dependence, remains unknown. Here, we demonstrate that naloxone-precipitated morphine withdrawal in mice altered de novo sphingolipid metabolism in the dorsal horn of the spinal cord and increased S1P that accompanied the manifestation of several withdrawal behaviors. Blocking de novo sphingolipid metabolism with intrathecal administration of myriocin, an inhibitor of serine palmitoyltransferase, blocked naloxone-precipitated withdrawal. Noteworthy, we found that competitive (NIBR-15) and functional (FTY720) S1PR1 antagonists attenuated withdrawal behaviors in mice. Mechanistically, at the level of the spinal cord, naloxone-precipitated withdrawal was associated with increased glial activity and formation of the potent inflammatory/neuroexcitatory cytokine interleukin-1β (IL-1β); these events were attenuated by S1PR1 antagonists. These results provide the first molecular insight for the role of the S1P/S1PR1 axis during opioid withdrawal. Our data identify S1PR1 antagonists as potential therapeutics to mitigate opioid-induced dependence and support repurposing the S1PR1 functional antagonist FTY720, which is FDA-approved for multiple sclerosis, as an opioid adjunct.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Doyle TM,Hutchinson MR,Braden K,Janes K,Staikopoulos V,Chen Z,Neumann WL,Spiegel S,Salvemini Ddoi
10.1186/s12974-020-01975-2subject
Has Abstractpub_date
2020-10-22 00:00:00pages
314issue
1issn
1742-2094pii
10.1186/s12974-020-01975-2journal_volume
17pub_type
杂志文章abstract：BACKGROUND:Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system that preferentially affects the optic nerves, spinal cord, and area postrema. A series of evidence suggested that B cells play a fundamental role in the pathogenesis of NMOSD. However, there are...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-017-0961-z
更新日期：2017-09-25 00:00:00
abstract：BACKGROUND:In sepsis syndromes the severity of the inflammation triggers microvascular dysfunction and early organ failure. We studied the effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculatory integrity in an endotoxinemic rat model. METHODS:In both control and endotoxinemic (5 mg/kg li...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-9-183
更新日期：2012-07-25 00:00:00
abstract：BACKGROUND:The cause of neurodegeneration in progressive forms of multiple sclerosis is unknown. We investigated the impact of specific neuroinflammatory markers on human neurons to identify potential therapeutic targets for neuroprotection against chronic inflammation. METHODS:Surface immunocytochemistry directly vis...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-017-0901-y
更新日期：2017-06-27 00:00:00
abstract：BACKGROUND:Genetic and environmental factors are critical elements influencing the etiology of major depression. It is now accepted that neuroinflammatory processes play a major role in neuropsychological disorders. Neuroinflammation results from the dysregulation of the synthesis and/or release of pro- and anti-inflam...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-11-132
更新日期：2014-07-28 00:00:00
abstract：BACKGROUND:Recent evidence suggests that exposure to intrauterine inflammation causes acute fetal brain injury and is linked to a spectrum of neurobehavioral disorders. In a rodent model of intrauterine inflammation induced by lipopolysaccharide (LPS) exposure in utero, activated microglia can be detected in the hippoc...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-017-0951-1
更新日期：2017-09-05 00:00:00
abstract：BACKGROUND:HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cel...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-11-53
更新日期：2014-03-22 00:00:00
abstract：BACKGROUND:There are reasons to expect an association with Alzheimer's disease (AD) within the HLA region. The HLA-B & C genes have, however, been relatively understudied. A geographically specific association with HLA-B7 & HLA-Cw*0702 had been suggested by our previous, small study. METHODS:We studied the HLA-B & C a...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-3-33
更新日期：2006-12-18 00:00:00
abstract：BACKGROUND:Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. OBJECTIVE:The objective of this study is to investigate whether...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-017-0899-1
更新日期：2017-06-24 00:00:00
abstract：BACKGROUND:Alzheimer's disease (AD) is a multifactorial disorder associated with the accumulation of soluble forms of beta-amyloid (Aβ) and its subsequent deposition into plaques. One of the major contributors to neuronal death is chronic and uncontrolled inflammatory activation of microglial cells around the plaques a...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-014-0229-9
更新日期：2015-01-16 00:00:00
abstract：BACKGROUND:Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states-the classically activated M1 phenotype that confers pro-inflammatory effects or the alternativ...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-018-1183-8
更新日期：2018-05-22 00:00:00
abstract：BACKGROUND:Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties. In this study, we aimed to assess andrographolide's potential utility as an anti-neuroinflammatory therapeutic. METHODS:The effects of andro...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-016-0498-6
更新日期：2016-02-09 00:00:00
abstract：BACKGROUND:Granulocyte colony-stimulating factor (G-CSF) is a pharmacologic agent inducing neutrophil mobilization and a new candidate for neuroprotection and neuroregeneration in stroke. Its effects when used in combination with tissue plasminogen activator (tPA) were explored during the acute phase of ischemic stroke...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-11-96
更新日期：2014-05-27 00:00:00
abstract：BACKGROUND:Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here,...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-018-1224-3
更新日期：2018-06-22 00:00:00
abstract：INTRODUCTION:We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of th...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-9-228
更新日期：2012-09-28 00:00:00
abstract：BACKGROUND:Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanami...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-020-02022-w
更新日期：2020-11-22 00:00:00
abstract：BACKGROUND:Neuroinflammation is considered a risk factor for impairments in neuronal function and cognition that arise with trauma, infection, and/or disease. IL-17A has been determined to be involved in neurodegenerative diseases such as multiple sclerosis. Recently, IL-17A has been shown to be upregulated in lipopoly...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-015-0394-5
更新日期：2015-09-15 00:00:00
abstract：BACKGROUND:Monocyte infiltration is involved in the pathogenesis of many retinal degenerative conditions. This process traditionally depends on local expression of chemokines, though the roles of many of these in the degenerating retina are unclear. Here, we investigate expression and in situ localization of the broad ...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-014-0224-1
更新日期：2015-01-17 00:00:00
abstract：BACKGROUND:The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown t...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-016-0539-1
更新日期：2016-04-05 00:00:00
abstract：BACKGROUND:Interleukin-1 (IL-1) is a key mediator of ischaemic brain injury induced by stroke and subarachnoid haemorrhage (SAH). IL-1 receptor antagonist (IL-1Ra) limits brain injury in experimental stroke and reduces plasma inflammatory mediators associated with poor outcome in ischaemic stroke patients. Intravenous ...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1186/1742-2094-11-1
更新日期：2014-01-03 00:00:00
abstract：BACKGROUND:White matter injury (WMI) is the major antecedent of cerebral palsy in premature infants, and is often associated with maternal infection and the fetal inflammatory response. The current study explores the therapeutic potential of glutamate receptor blockade or cyclooxygenase-2 (COX-2) inhibition for inflamm...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-10-153
更新日期：2013-12-17 00:00:00
abstract：BACKGROUND:Necrotizing enterocolitis (NEC) is an acute gut inflammatory disorder that occurs in preterm infants in the first weeks after birth. Infants surviving NEC often show impaired neurodevelopment. The mechanisms linking NEC lesions with later neurodevelopment are poorly understood but may include proinflammatory...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-018-1201-x
更新日期：2018-06-09 00:00:00
abstract：BACKGROUND:A dose-limiting side effect of chemotherapeutic agents such as vincristine (VCR) is neuropathic pain, which is poorly managed at present. Chemokine-mediated immune cell/neuron communication in preclinical VCR-induced pain forms an intriguing basis for the development of analgesics. In a murine VCR model, CX3...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-018-1116-6
更新日期：2018-04-06 00:00:00
abstract：BACKGROUND:This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS:Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-017-1037-9
更新日期：2018-01-04 00:00:00
abstract：BACKGROUND:Epilepsy is a common and debilitating consequence of traumatic brain injury (TBI). Seizures contribute to progressive neurodegeneration and poor functional and psychosocial outcomes for TBI survivors, and epilepsy after TBI is often resistant to existing anti-epileptic drugs. The development of post-traumati...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章,评审
doi：10.1186/s12974-016-0786-1
更新日期：2017-01-13 00:00:00
abstract：:Human immunodeficiency virus type 1 (HIV) continues to be one of the most prevalent global health afflictions to date. The advent and introduction of combined antiretroviral therapy (cART) has made a significant impact on the course of infection. However, as patients are living longer, many HIV-associated illnesses ar...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章,评审
doi：10.1186/1742-2094-10-144
更新日期：2013-12-01 00:00:00
abstract：BACKGROUND:The chemokine interleukin-8 (IL-8) and its receptor CXCR2 contribute to chemotactic responses in Alzheimer's disease (AD); however, properties of the ligand and receptor have not been characterized in animal models of disease. The primary aim of our study was to examine effects of pharmacological antagonism ...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-015-0339-z
更新日期：2015-08-09 00:00:00
abstract：BACKGROUND:CD8+ T lymphocytes are critical mediators of neuroinflammatory diseases. Understanding the mechanisms that govern the function of this T cell population is crucial to better understanding central nervous system autoimmune disease pathology. We recently identified a novel population of highly cytotoxic c-Met-...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-019-1676-0
更新日期：2020-02-19 00:00:00
abstract：OBJECTIVES:The neurological basis for autism is still not fully understood, and the role of the interaction between neuro-inflammation and neurotransmission impairment needs to be clearer. This study aims to test the possible association between impaired levels of gamma aminobutyric acid (GABA), serotonin, dopamine, ox...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-11-4
更新日期：2014-01-08 00:00:00
abstract：BACKGROUND:Noradrenaline (NA) is known to limit neuroinflammation. However, the previously described induction by NA of a chemokine involved in the progression of immune/inflammatory processes, such as chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein-1 (MCP-1), apparently contradicts NA anti-inflammat...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/1742-2094-10-81
更新日期：2013-07-09 00:00:00
abstract：BACKGROUND:The early dysfunction and subsequent recovery after stroke, characterized by the destruction and remodeling of connective pathways between cortex and subcortical regions, is associated with neuroinflammation. As major components of the inflammatory process, reactive astrocytes have double-edged effects on pa...
journal_title：Journal of neuroinflammation
pub_type： 杂志文章
doi：10.1186/s12974-016-0622-7
更新日期：2016-06-18 00:00:00
