Effects of nuclear factor erythroid 2-related factor 2 (NFE2L2) on antinociceptive effects of dimethyl fumarate. (A) Beginning 14 days after spared nerve injury (SNI) or sham surgery, the NFE2L2 inhibitor trigonelline (300 mg/kg; twice per day) or vehicle was administered together with dimethyl fumarate (300 mg/kg; once per day) or vehicle for 5 days. Von Frey thresholds for mechanical allodynia are presented. n = 5 rats in the sham-vehicle-trigonelline and SNI-vehicle-trigonelline groups; n = 6 rats in all other groups (B, C) Ipsilateral L4/5 dorsal root ganglia (DRG) were collected after 5 days of oral coadministration of the NFE2L2 inhibitor trigonelline (300 mg/kg; twice per day) or vehicle with dimethyl fumarate (300 mg/kg; once per day) or vehicle (Veh), which began 14 days after SNI surgery. NFE2L2 and nuclei were immunofluorescently labeled in DRG sections. (B) The number of 4′,6-diamidino-2-phenylindole (DAPI)-positive nuclei colocalized with NFE2L2 are expressed as a percentage of the total number of nuclei in each section. DRG from n = 6 rats/group. (C) Representative fluorescent photomicrographs are presented (40×). Scale bar = 50 μm. (D) Beginning 7 days after SNI surgery, dimethyl fumarate (300 mg/kg; once per day) was administered for 5 days to wild type or Nfe2l2^-/- male and female mice (n = 4 per sex). Von Frey thresholds for mechanical allodynia are presented with data pooled from both sexes. Data are mean ± SD; *P < 0.05, **P < 0.01, ***P < 0.001.