Recombinant protein transduction domain-Cu/Zn superoxide dismutase alleviates bone cancer pain via peroxiredoxin 4...

Bone cancer pain (BCP) is a serious chronic clinical condition and reactive oxygen species (ROS) were considered to be involved in its development and persistency. Normally, superoxide dismutase (SOD) converts superoxide anions to hydrogen peroxide (H₂O₂) and H₂O₂ is then naturalized to be water by peroxiredoxin 4. We reported previously that recombinant protein transduction domain (PTD)-Cu/Zn SOD effectively scavenged excessive ROS and prevented cardiomyocytes from hypoxia-reoxygenation damage. However, whether PTD-Cu/Zn SOD would prevent BCP development is unknown. In the current study, we found that an implanted carcinoma in the rat tibia induced remarkable hyperalgesia, increased H₂O₂ levels and decreased SOD and peroxiredoxin 4 levels. After administration of recombinant PTD-Cu/Zn SOD to these tumor-burden rats, their hyperalgesia was significantly attenuated and peroxiredoxin 4 expression was significantly increased. In addition, an increased expression of N-methyl-d-aspartic acid (NMDA) receptors and a decreased expression of γ-aminobutyric acid (GABA) receptors in this cancer pain were prevented by PTD-Cu/Zn SOD administration or peroxiredoxin 4 overexpression. Our data suggested that reactive oxygen species, at least in part, play a role in cancer metastatic pain development and persistency which can be attenuated by the adminstration of recombinant PTD-Cu/Zn SOD via the peroxiredoxin 4 modulation from oxidative stress.