It has been suggested that reactive oxygen species (ROS) play an important role in
‘central sensitization’, a critical mechanism underlying persistent pain, via increases in
NMDA receptor phosphorylation in the spinal cord dorsal horn.7) ROS can be generated by
activation of the NADPH oxidase (Nox) enzyme.8) Among six homologs, the NADPH
oxidase 2 (Nox2) isoform has been indicated as the main source of ROS in neurons, which
produces superoxide following neuronal NMDA receptor activation.9,10) Nox2 is a highly
regulated membrane bound enzyme complex that is composed of membrane-bound subunits
(p22phox and gp91phox) and cytosolic subunits (p40phox, p47phox, and p67phox) as well as the small GTPase Rac. The cytosolic components translocate to the cell membrane in order to
form a functional active enzyme complex.11,12) In particular p47phox has an important role in
both translocation and assembly, by which Nox enzyme activation is initiated.10) In a
previous study, we demonstrated that spinal Sig-1R activation increases p47phox
translocation to the membrane fraction and concomitant ROS production.13) However, it
remains unclear whether Nox2-derived ROS mediates Sig-1R-induced potentiation of
NMDA receptor function