Repeated Administration of Mirtazapine Attenuates Oxaliplatin-Induced Mechanical Allodynia and Spinal NR2B Up-Regulation in Rats

Abstract

Chemotherapic drugs may elicit acute or chronic peripheral neuropathies. Mirtazapine, as an antidepressant, is also used for the treatment of neuropathic pain. The current study aimed to investigate the effect of mirtazapine on the oxaliplatin-induced neuropathy in rats as well as the underlying mechanism. A neuropathy model was established in Sprague-Dawley rats by intraperitoneal (i.p.) injection of oxaliplatin 4mg/kg twice a week for 4weeks. The therapeutic potential of mirtazapine 10, 20, and 30mg/kg/day per-orally for 28 consecutive days was evaluated. Subsequently, a dose of 1mg/kg of WAY100635 i.p., a selective antagonist of 5-HT1A receptor, was preadministrated before mirtazapine 20mg/kg/day per-orally in oxaliplatin-induced neuropathy. The behavioral tests and the expression of NMDA receptor subunit NR2B were determined. The results displayed that repeated administration of mirtazapine 20 or 30mg/kg/day for 28 consecutive days significantly attenuated the mechanical allodynia and the up-regulation of spinal cord NR2B but not the cold hyperalgesia in rats with oxaliplatin-induced neuropathy, which was reversed by WAY100635 preadministration. Our findings suggest that oxaliplatin-induced mechanical allodynia is associated with spinal NR2B up-regulation, which may be attenuated by mirtazapine administration.