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      Remimazolam alleviates neuropathic pain via regulating bradykinin receptor B1 and autophagy

      1 , 1 , 2 , 1 , 1 , 1
      Journal of Pharmacy and Pharmacology
      Oxford University Press (OUP)

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          Abstract

          Objectives

          Neuropathic pain (NP) represents a broad scope of various pathological ramifications of the nervous system. Remimazolam is a proved sedative in treating neuropathic pain. Considering the Bradykinin receptor’s vital role and the potentials of Bradykinin receptor B1 (BDKRB1) in the neuropathic pain-signalling pathway, we nominated them as a primary target for remimazolam.

          Methods

          In this study, rats were injected with complete freund’s adjuvant (CFA) to construct NP models in vivo. BV2 microglia cells were treated with LPS to establish NP model in vitro. qRT-PCR, ELISA, western blot and immunofluorescence were applied to determine gene expression.

          Key findings

          Our findings revealed that BDKRB1 was overexpressed in NP models in vivo, while R715 (an antagonist of BDKRB1) suppressed the levels of BDKRB1 and inhibited the hyperpathia induced by spinal nerve litigation surgery. Moreover, remimazolam inactivated BDKRB1 signalling via suppressing NF-κB translocation and decreased the release of pro-inflammatory cytokines. Additionally, remimazolam suppressed the translocation of NF-κB, and inhibited autophagic lysosome formation in vivo and in vitro. However, R838 (an agonist of BDKRB1) reversed the effects of remimazolam.

          Conclusions

          Remimazolam downregulated BDKRB1, inhibited BDKRB1/RAS/MEK signalling pathway and regulated the autophagic lysosome induction, exhibiting a better outcome in the NP.

          Related collections

          Most cited references37

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          Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

          New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis.
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            Mechanisms of neuropathic pain.

            Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms. Neuropathic pain reflects both peripheral and central sensitization mechanisms. Abnormal signals arise not only from injured axons but also from the intact nociceptors that share the innervation territory of the injured nerve. This review focuses on how both human studies and animal models are helping to elucidate the mechanisms underlying these surprisingly common disorders. The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders.
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              • Record: found
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              • Article: not found

              Role of the immune system in chronic pain.

              During the past two decades, an important focus of pain research has been the study of chronic pain mechanisms, particularly the processes that lead to the abnormal sensitivity - spontaneous pain and hyperalgesia - that is associated with these states. For some time it has been recognized that inflammatory mediators released from immune cells can contribute to these persistent pain states. However, it has only recently become clear that immune cell products might have a crucial role not just in inflammatory pain, but also in neuropathic pain caused by damage to peripheral nerves or to the CNS.
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                Author and article information

                Contributors
                Journal
                Journal of Pharmacy and Pharmacology
                Oxford University Press (OUP)
                0022-3573
                2042-7158
                June 01 2021
                June 01 2021
                Affiliations
                [1 ]Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical College, Zhanggong District, Ganzhou City, Jiangxi Province, China
                [2 ]Department of Anesthesiology, Xingguo People’s Hospital, Xingguo County, Ganzhou City, Jiangxi Province, China
                Article
                10.1093/jpp/rgab080
                34061162
                78154c0e-32ec-47a3-aea5-2d8d75acf84d
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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