Role of NADPH oxidase-mediated activation of microglia in the comorbidity of neuropathic pain and depression / 临床麻醉学杂志

ABSTRACT

Objective To observe the variation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and microglia in the comorbidity of neuropathic pain and depression and discuss the related mechanism.Methods The spared nerve injury model was used.Forty-four male adult Sprague Dawley rats were randomly divided into the following four groups (n=11 each): sham+vehicle group (group SV), sham+APO group (group SA), SNI+vehicle group (group SNV), SNI+APO group (group SNA).In groups SA and SNA, rats were intraperitoneally injected with apocynin (APO) 15 mg/kg 24 hours and 1 hour before SNI and continued once daily until the 14th day.The rats in the other two groups received the equal volume of vehicle.The mechanical withdrawal threshold (MWT) was tested 1 day before SNI and 7 days and 14 days after SNI, and the open field test, the forced swimming test and the sucrose preference test were performed 14 days after SNI.The prefrontal cortex were collected 2 hour after the behavior tests.The expression of gp91phox was detected by Western blot and the expression of Iba1 and gp91phox were detected by double-immunofluorescance staining.Results The reduced MWT, the increased immobility time, the decreased sucrose consumption and the increased content of gp91phox were observed in group SNV compared with groups SV, SA and SNA (P<0.05).The expression of Iba1 and gp91phox were increased in group SNV.The total travel distance in the open field test and the total liquid consumption in the sucrose preference test had no significant difference among the four groups.Conclusion Neuropathic pain may induce depressive behaviors and activate NADPH oxidase in the prefrontal cortex.Moreover, the inhibition of NADPH oxidase by APO can alleviate neuropathic pain and depression, which is potentially related to the activation of microglia.