P2X7 receptor antagonist BBG inhibits endoplasmic reticulum stress and pyroptosis to alleviate postherpetic neuralgia

Zhu, Yuyou; Zhang, Siping; Wu, Yuanbo; Wang, Juan

doi:10.1007/s11010-021-04169-3

Cited by 13 publications

(10 citation statements)

References 25 publications

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“…This PHN model has been extended by others, indicative that the pain state lasts for a longer time, and in behaviour tests measuring affective pain responses (12,24,(27)(28)(29)32). Rats consistently developed mechanical hyperalgesia from the first week following injection (12,(25)(26)(27)(28)(29)(30)(31)(32), and the pain lasted for several weeks, and gradually relieved within 90 days after VZV injection. Mechanical allodynia has been proved to be irrelevant by viral strains but in a dose-dependent pattern during pain development (10).…”

Section: The Development Of Phn Rodent Models and Pain Evaluations Vz...mentioning

confidence: 86%

Rodent models of postherpetic neuralgia: How far have we reached?

Chen

Yang

et al. 2023

Front. Immunol.

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BackgroundInduced by varicella zoster virus (VZV), postherpetic neuralgia (PHN) is one of the common complications of herpes zoster (HZ) with refractory pain. Animal models play pivotal roles in disclosing the pain mechanisms and developing effective treatments. However, only a few rodent models focus on the VZV-associated pain and PHN.ObjectiveTo summarize the establishment and characteristics of popular PHN rodent models, thus offer bases for the selection and improvement of PHN models.DesignIn this review, we retrospect two promising PHN rodent models, VZV-induced PHN model and HSV1-induced PHN model in terms of pain-related evaluations, their contributions to PHN pathogenesis and pharmacology.ResultsSignificant difference of two PHN models is the probability of virus proliferation; 2) Most commonly used pain evaluation of PHN model is mechanical allodynia, but pain-induced anxiety and other behaviours are worth noting; 3) From current PHN models, pain mechanisms involve changes in virus gene and host gene expression, neuroimmune–glia interactions and ion channels; 4) antiviral drugs and classical analgesics serve more on the acute stage of herpetic pain.ConclusionsDifferent PHN models assessed by various pain evaluations combine to fulfil more comprehensive understanding of PHN.

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Section: The Development Of Phn Rodent Models and Pain Evaluations Vz...mentioning

confidence: 86%

Rodent models of postherpetic neuralgia: How far have we reached?

Chen

Yang

et al. 2023

Front. Immunol.

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“…P2X7 receptor antagonist BBG can inhibit pyroptosis to alleviate postherpetic neuralgia (Zhu et al. 2021 ). Inhibition of calpain alleviates coxsackievirus B3-induced myocarditis by suppressing the canonical NLRP3 inflammasome/caspase-1-mediated pyroptosis pathways (Yu et al.…”

Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription JieZe-1 in protecting against HSV-2 infection

Liu

Shao

Wang

et al. 2022

Pharmaceutical Biology

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Context The Chinese herbal prescription JieZe-1 (JZ-1) is effective against HSV-2 ( Herpes simplex virus type 2) infection. However, its mechanism remains unclear. Objective To explore the mechanism of JZ-1 in protecting against HSV-2 infection. Materials and methods Using the methods of network pharmacology, the hub components and targets were screened and functionally enriched. We established a genital herpes (GH) mouse model and observe the disease characteristics. Then, the GH mice in different groups (10 per/group) were treated with 20 μL JZ-1 gel (2.5, 1.5, and 0.5 g/mL), acyclovir gel (0.03 g/mL), or plain carbomer gel twice a day. The symptom score, vulvar histomorphology, and virus load were measured. The critical proteins of caspase-1–dependent pyroptosis were analysed by microscopy, co-immunoprecipitation, western blotting, and ELISA. Molecular docking was also performed. Results Network pharmacology analysis identified 388 JZ-1 targets related to HSV-2 infection, with 36 hub targets and 21 hub components screened. The TCID 50 of HSV-2 was 1 × 10 −7 /0.1 mL. JZ-1 gel (2.5 g/mL) can effectively reduce the symptom score (81.23%), viral load (98.42%) and histopathological changes, and significantly inhibit the proteins expression of caspase-1–dependent pyroptosis in GH mice ( p< 0.05). The molecular docking test showed a good binding potency between 11 components and caspase-1 or interleukin (IL)-1β. Discussion and conclusions The present study demonstrated that JZ-1 protected mice from HSV-2 infection and inhibit the caspase-1–dependent pyroptosis in GH mice. It is of significance for the second development of JZ-1 and the exploration of new drugs.

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“…Very little is known about the impact of inflammasome activation in VZV disease in humans, but an investigation with human skin xenografts in a SCID mouse model of VZV revealed that NLRP3 was induced in cells within VZV lesions, suggesting that VZV-induced inflammasome activation takes place in vivo ( 58 ). More recently, a study found that pharmacologically reducing endoplasmic reticulum stress in a rat model of VZV-associated post-herpetic neuralgia (PHN) led to decreased IL-1β and IL-18 release and improved PHN scores, suggesting that long term activation of the inflammasome is associated with more severe VZV-induced PHN ( 59 ). This, combined with the results for HSV-1 which demonstrate a detrimental effect of inflammasome activation (particularly in encephalitis), suggest a model where inflammasome activation in the periphery helps control viral replication, but inflammasome signaling in neuronal tissue leads to pathological inflammation that is harmful to the host.…”

Section: Inflammasome Activation Has Variable Impact On Diseases Caused By Herpesvirusesmentioning

confidence: 99%