ABSTRACT
Objective To investigate the change of spinal G protein-coupled receptor kinase 2 (GRK2) expression in persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) in rats.Methods 40 male Sprague Dawley (SD) rats were divided into 2 groups (n =20) using a random number table:sham operation group and skin/muscle incision and retraction group (SMIR group).A rat model of peristent postoperativepain evoked by SMIR was made according to the method described by Flatters.Pain behavior was assessed by paw mechanical withdrawal threshold (MWT) to yon Frey filament stimulationintensity at 1 d before operation (T0) and 3 d (T1),7 d (T2),14 d (T3) and 21 d (T4) after operation.4 rats in each group were sacrificed at T0-4,the L4-L6 segments of the spinal cord were obtained for determination of GRK2 expression in the spinal cord by Western blot.Results Compared with T0,the MWT was significantly decreased and the expression of spinal GRK2 was down-regulated at T1-T4 in SMIR group (P ＜ 0.05).Compared with sham operation group,the MWT and the expression of spinal GRK2 was decreased at T1-T4 in SMIR group (P ＜ 0.05).Conclusions The down-regulation of expression of spinal GRK2 may be involved in the development and maintenance of persistent postoperative pain in rats evoked by SMIR.
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.