Mechanism and effects of NMDA receptor NR1 subunit on chronic constriction injury-induced neuropathic pain in a rat model / 中国医师杂志

ABSTRACT

Objective To investigate the effects of intrathecal injection (IT) of agonist and antagonist of N-methyl-D-aspartate receptor subunit 1 (NMDA NR1) on pain threshold and spinal levels of glutamate and glutamate transporter-1 (GLT-1) in rat model of chronic constriction injury (CCI) induced neuropathic pain.Methods Sprague-Dawley (SD) rats were randomly divided into 4 groups (Sham,CCI,NM-DA,and Humanin).The CCI model was established by right sciatic nerve constriction.The thermal and mechanical thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and yon Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after CCI.The NMDA and Humanin groups were administered intrathecally for 3 days before surgery.Spinal expression of GLT-1 assessed by Weston blotting and levels of glutamate were measured by enzyme-linked immunosorbent assay (ELISA).Results Compared to Sham group,the rats in CCI group gradually appeared the symptoms of toe close together,foot valgus and repeated licking to the operative side of the hind legs after surgery,and the paw withdrawal threshold (PWT),and PWL were greatly decreased,reaching the lowest level on the 7th day.Meanwhile,the glutamate content was increased,and the GLT-1 expression was decreased in spinal cord (P ＜ 0.05).Compared to CCI group,the rats in NMDA group were observed with further decrease in PWT,PWL and GLT-1 expressions at all observed timepoints (P ＜ 0.05),but increase in glutamate content in spine cord (P ＜0.05).Compared to CCI group,the rats in Humanin group were observed with increase in PWT,PWL and GLT-1 expressions at all observed timepoint (P ＜ 0.05),but decrease in glutamate content in spine cord (P ＜ 0.05).Conclusions NMDA receptor NR1 subunit participated in regulating neuropathic pain,inhibiting NMDA receptor NR1 subunit can alleviate neuropathic pain by down-regulating of glutamate and GLT-1.