Association between decreased expression of GLT‐1 derived spinal glutamate accumulation and oxaliplatin‐induced mechanical allodynia (1143.1)

Oxaliplatin (L‐OHP) is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. We reported that NMDA receptors in spinal cord is involved in mechanical allodynia induced by L‐OHP (4 mg/kg, i.p., twice a week). In this study, we investigated the involvement of spinal glutamate in L‐OHP‐induced mechanical allodynia more closely. The L‐OHP‐induced mechanical allodynia was reversed not only by a NMDA receptor antagonist MK‐801 but also by an AMPA receptor antagonist NBQX. In vivo microdialysis, formalin‐induced nociception (5% formalin, 50µL, s.c.) sustainably increased extracellular glutamate concentration in the spinal cord in L‐OHP‐treated rats compared to vehicle‐treated rats, whereas tactile stimuli (brushing stimulation) increased extracellular glutamate concentration in the spinal cord in L‐OHP‐treated rats alone. Moreover, GLT‐1 (Glutamate transporter 1) but not GLAST (Glial glutamate transporter) and EAAC1 (Excitatory amino‐acid carrier 1), was decreased in the spinal cord dorsal horn in L‐OHP‐treated rats. These results suggest that L‐OHP inhibits uptake of extracellular glutamate by down‐regulation of GLT‐1 expression and increased accumulation of glutamate in the spinal cord.