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

Autores da FMUP

• Teresa Maria De Jesus Teixeira De Sousa

  Autor

• Dora Raquel Da Silva Pinho

  Autor

Participantes de fora da FMUP

• Teixeira Santos, L
• Verissimo, E
• Martins, S
• Albino-Teixeira, A

Unidades de investigação

• Biomedicina

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-1 beta, 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.

Keywords

• neuropathic pain; spared nerve injury; NOX2; GSK2795039; pain-related behavior; neuroinflammation; sex differences