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Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.

ABSTRACT: NADPH oxidase isoform-2 (NOX2) has been implicated in the pathophysiology of neuropathic pain (NP), mostly through the modulation of neuroinflammation. Since it is also accepted that some neuroimmune mechanisms underlying NP are sex-dependent, we aimed to evaluate the effects of early systemic treatment with the NOX2-selective inhibitor (NOX2i) GSK2795039 on behavioral responses and spinal neuroinflammation in spared nerve injury (SNI)-induced NP in male and female mice. Mechanical sensitivity was evaluated with the von Frey test, while general well-being and anxiety-like behavior were assessed with burrowing and light/dark box tests. Spinal microglial activation and cytokines IL-1β, IL-6, and IL-10, as well as macrophage colony-stimulating factor (M-CSF) were evaluated by immunofluorescence and multiplex immunoassay, respectively. NOX2i treatment reduced SNI-induced mechanical hypersensitivity and early SNI-induced microglial activation in both sexes. SNI-females, but not males, showed a transient reduction in burrowing activity. NOX2i treatment did not improve their burrowing activity, but tendentially reduced their anxiety-like behavior. NOX2i marginally decreased IL-6 in females, and increased M-CSF in males. Our findings suggest that NOX2-selective inhibition may be a potential therapeutic strategy for NP in both male and female individuals, with particular interest in females due to its apparent favorable impact in anxiety-like behavior.

SUBMITTER: Teixeira-Santos L

PROVIDER: S-EPMC9953009 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.

Teixeira-Santos Luísa L Veríssimo Eduardo E Martins Sandra S Sousa Teresa T Albino-Teixeira António A Pinho Dora D

Biomedicines 20230131 2

NADPH oxidase isoform-2 (NOX2) has been implicated in the pathophysiology of neuropathic pain (NP), mostly through the modulation of neuroinflammation. Since it is also accepted that some neuroimmune mechanisms underlying NP are sex-dependent, we aimed to evaluate the effects of early systemic treatment with the NOX2-selective inhibitor (NOX2i) GSK2795039 on behavioral responses and spinal neuroinflammation in spared nerve injury (SNI)-induced NP in male and female mice. Mechanical sensitivity w ...[more]

PMID: 36830952

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Dataset Information

Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.

Publications

Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.

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