Gabapentin prevents oxaliplatin-induced central sensitization in the dorsal horn neurons in rats

Objective(s): The present study aims to study the alteration of glutamatergic transmission in the dorsal horn neurons and the effect of gabapentin on oxaliplatin-induced neuropathic pain in rats. Materials and Methods: Oxaliplatin (5 mg/kg) or saline was administered to adult male Sprague-Dawley rats.  Gabapentin (60 mg/kg, IP) or vehicle was injected daily. Mechanical allodynia was assessed using a series of von Frey filaments. The expression of glutamate receptor subunits (NR2B and GluR1) and brain-derived neurotrophic factor (BDNF) was measured in the dorsal horn. The glutamatergic strength was recorded in the spinal cord slices. Results: Administration of oxaliplatin induced significant hyperreactivity to mechanical stimuli in rats, which was attenuated by gabapentin. Significant increase in the expression of BDNF was found in the dorsal horn in rats receiving oxaliplatin, which was prevented by gabapentin. Further studies also observed a significant increase in the expression of GluR1 and NR2B, as well as enhanced glutamatergic transmission in the dorsal horn neurons in rats treated with oxaliplatin. The upregulation of glutamatergic transmission was significantly reversed by gabapentin. Conclusion: These results illustrated an increased expression of BDNF and enhanced glutamatergic transmission in rats with oxaliplatin-induced neuropathic pain, which was markedly attenuated by gabapentin.