BAY-117082-driven NLRP3 inflammasome inhibition resolves nitro-glycerine (NTG) neuronal damage in in vivo model of migraine

Filippone, Alessia; Scuderi, Sarah Adriana; Basilotta, Rossella; Lanza, Marika; Casili, Giovanna; Bova, Valentina; Paterniti, Irene; Esposito, Emanuela

doi:10.1016/j.biopha.2022.113851

Cited by 12 publications

(12 citation statements)

References 52 publications

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“…Across the research included in this review, a variety of outcome measures were observed, such as behavioral tests ( n = 9; 40.09%) ( 30 , 70 , 74–76 ), Sensory sensitivity testing ( 28 ), von Frey Testing ( 27 , 77 ), Light/dark test ( 27 ), Von frey test ( 27 ). To check the specific biomarker estimation ELISA ( n = 8; 36.36%) ( 30 , 31 , 72 , 74 , 75 , 77–79 ), Western blot analysis ( n = 9; 40.09%) ( 28 , 70 , 73–75 , 79–83 ), immunohistochemistry ( n = 4; 18.18%) ( 72 , 73 , 75 , 77 , 78 , 81 , 82 ), Histopathology ( 27 ), Immunofuorescence staining ( n = 9; 40.09%) ( 27 , 28 , 30 , 31 , 70 , 76 , 78 ), and for gene expression used qRT PCR ( n = 7; 31.81%) ( 27 , 28 , 31 , 70 , 74 , 77 , 78 , 80 , 81 , 83 ). The majority of researchers, around 60–70%, neglect to validate their experiments using behavioral tests, Western blotting, Immunofluorescence, and Immunohistochemistry, despite these tests being crucial for experimental validation.…”

Section: Resultsmentioning

confidence: 99%

“…Their critical findings indicate that NLRP3 is capability to mature IL1-β and is involved in the production of IL-10. Elevated levels of neurotrophic factors, particularly BDNF, may also influence NTG through the CREB/Erk/Akt pathways ( 27 , 28 , 30 , 70 , 75 , 82 ). In the context of a neuropathic pain model, S1PR1 on glial cells influenced various downstream signaling pathways, including the MAPK pathways and the NLRP3 inflammasomes ( 85–87 ).…”

Section: Discussionmentioning

confidence: 99%

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A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

Rushendran,

Singh,

Ankul Singh

et al. 2024

Front. Neurol.

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BackgroundMigraines affect one billion individuals globally, with a higher occurrence among young adults and women. A significant survey in the United States indicated that 17.1% of women and 5.6% of men suffer from migraines. This study seeks to investigate the potential connection between NLRP3 and MMP9 in migraine pathology.MethodsThe research involved searching databases such as PubMed, Scopus, Science Direct, Google Scholar, and Proquest, with the search concluding on March 31, 2024. Following PRISMA guidelines, PICO data were collected, focusing exclusively on animal models induced by Nitroglycerine (10 mg/kg), while excluding clinical studies.ResultsThe study, originally registered in Prospero Reg. No. CRD42022355893, conducted bias analysis using SYRCLE’s RoB tool and evaluated author consensus using GraphPad v9.5.1. Out of 7,359 search results, 22 papers met the inclusion criteria. Inter-rater reliability among reviewers was assessed using Cohen’s kappa statistics.ConclusionThis review summarizes 22 preclinical studies on Nitroglycerin (NTG), NLRP3, MMP9, and related biomarkers in migraine. They reveal that NTG, especially at 10 mg/kg, consistently induces migraine-like symptoms in rodents by activating NLRP3 inflammasome and stimulating proinflammatory molecule production.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, CRD42022355893.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

Rushendran,

Singh,

Ankul Singh

et al. 2024

Front. Neurol.

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“…The simultaneous monitoring of changes in the brain tissue accompanying stimulus-dependent and independent pain behavior provides a more global view of the role that NLRP3 inflammasome plays in the development of persistent pain states. Although it is unknown to what degree the caspase-1-mediated signaling cascade and associated maturation of IL-1β or IL-18 contributes to the pathogenesis of pain states following mTBI [ 49 ], these proinflammatory cytokines have been identified in the TBI brain [ 16 , 43 , 50 ]. Indeed, IL-1β exerts its cellular effects by interacting with the cell surface (IL-1R) type I and type II receptors, with most effects mediated by IL-1RI, which in turn can elicit activation of p38 MAP [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Repeated closed-head mild traumatic brain injury-induced inflammation is associated with nociceptive sensitization

Nguyen,

Cochran

et al. 2023

J Neuroinflammation

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Background Individuals who have experienced mild traumatic brain injuries (mTBIs) suffer from several comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation in long-term pain after mTBIs is not fully elucidated. Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes in inflammatory processes following mTBIs and their effects on TBI-related pain. Methods We utilized a recently developed transgenic caspase-1 luciferase reporter mouse model to monitor caspase-1 activation through a thinned skull window in the in vivo setting following three closed-head mTBI events. Organotypic coronal brain slice cultures and acutely dissociated dorsal root ganglion (DRG) cells provided tissue-relevant context of inflammation signal. Mechanical allodynia was assessed by mechanical withdrawal threshold to von Frey and thermal hyperalgesia withdrawal latency to radiant heat. Mouse grimace scale (MGS) was used to detect spontaneous or non-evoked pain. In some experiments, mice were prophylactically treated with MCC950, a potent small molecule inhibitor of NLRP3 inflammasome assembly to inhibit injury-induced inflammatory signaling. Bioluminescence spatiotemporal dynamics were quantified in the head and hind paws, and caspase-1 activation was confirmed by immunoblot. Immunofluorescence staining was used to monitor the progression of astrogliosis and microglial activation in ex vivo brain tissue following repetitive closed-head mTBIs. Results Mice with repetitive closed-head mTBIs exhibited significant increases of the bioluminescence signals within the brain and paws in vivo for at least one week after each injury. Consistently, immunoblotting and immunofluorescence experiments confirmed that mTBIs led to caspase-1 activation, astrogliosis, and microgliosis. Persistent changes in MGS and hind paw withdrawal thresholds, indicative of pain states, were observed post-injury in the same mTBI animals in vivo. We also observed enhanced inflammatory responses in ex vivo brain slice preparations and DRG for at least 3 days following mTBIs. In vivo treatment with MCC950 significantly reduced caspase-1 activation-associated bioluminescent signals in vivo and decreased stimulus-evoked and non-stimulus evoked nociception. Conclusions Our findings suggest that the inflammatory states in the brain and peripheral nervous system following repeated mTBIs are coincidental with the development of nociceptive sensitization, and that these events can be significantly reduced by inhibition of NLRP3 inflammasome activation.

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“…In addition to neuropathic pain, migraine symptoms can be treated with analgesics that target the ERK/CREB pathway. BAY-117082, an NLRP3 inflammatory body inhibitor, can significantly reduce the expression of p-ERK, p-CREB, p-Akt, and p-PI3K to inhibit the ERK/CREB pathway and greatly lower the expression level of NLRP3 complex components such as IL-1β, IL-18 that play a role in alleviating pain attack and hyperalgesia in migraine mice ( Filippone et al, 2022 ).…”

Section: Analgesics Designed Based On Inhibition Of Erk/creb Pathwaymentioning

confidence: 99%

Mechanism of ERK/CREB pathway in pain and analgesia

Zhen

Wang

et al. 2023

Front. Mol. Neurosci.

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Research has long centered on the pathophysiology of pain. The Transient Receiver Potential (TRP) protein family is well known for its function in the pathophysiology of pain, and extensive study has been done in this area. One of the significant mechanisms of pain etiology and analgesia that lacks a systematic synthesis and review is the ERK/CREB (Extracellular Signal-Regulated Kinase/CAMP Response Element Binding Protein) pathway. The ERK/CREB pathway-targeting analgesics may also cause a variety of adverse effects that call for specialized medical care. In this review, we systematically compiled the mechanism of the ERK/CREB pathway in the process of pain and analgesia, as well as the potential adverse effects on the nervous system brought on by the inhibition of the ERK/CREB pathway in analgesic drugs, and we suggested the corresponding solutions.

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BAY-117082-driven NLRP3 inflammasome inhibition resolves nitro-glycerine (NTG) neuronal damage in in vivo model of migraine

Cited by 12 publications

References 52 publications

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

Repeated closed-head mild traumatic brain injury-induced inflammation is associated with nociceptive sensitization

Mechanism of ERK/CREB pathway in pain and analgesia

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