Downregulation of metallothionein-2 contributes to oxaliplatin-induced neuropathic pain

Abstract Background We previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here, we propose that MT2 within dorsal horns participates in development oxaliplatin-induced neuropathic may be pharmacological target for prevention treatment chemotherapy-induced peripheral neuropathy (CIPN). Methods The rat model CIPN was established by 5 consecutive injections (0.4 mg/100 g/day). Genetic restoration neuron-specific metallothionein-2 implemented 21 days before treatment, also, genetic inhibition siRNA performed. Mechanical allodynia locomotor activity were assayed. Cell-specific expression metallothionein-2, mRNA levels pro-inflammatory cytokines, nuclear translocation NF-?B, protein I?B-?, interaction I?B-? P65 evaluated horns. Also, vitro sequentially deleted promoter with used to assess signal transduction mechanism. Results found induced downregulation neurons. By contrast, horn neuron blocked reversed oxaliplatin-treated rats both sexes, whereas triggered normal rats. Overall not impaired alterations metallothionein-2. At molecular level, modulated neuroinflammation, activation inactive transcriptional promoter, these processes could Conclusions Metallothionein-2 is potential CIPN. A reduction NF-?B inflammatory responses enhancing transcription proposed