Inhibition of sigma-1 receptor reduces DRG cell apoptosis of rats with neuropathic pain

Abstract

Objective To investigate the effect of sigma-1 receptor (sig-1R) inhibition on apoptosis in the dorsal root ganglion (DRG) of rats with sciatic nerve chronic constriction injury (CCI)-mediated neuropathic pain. Methods Rats undergoing intrathecal intubation were randomly divided into three groups with 12 in each: sham group, model group (CCI modeling one week after intrathecal intubation) and sig-1R inhibitor group (BD1047 group) that was injected intrathecally on the fourth, fifth, and sixth days after the CCI operation. The mechanical withdrawal threshold (MWT) of rats was detected on the day before surgery and then first, third, fifth and seventh days after surgery. The expression of sig-1R, Bcl-2 and Bax was detected by Western blot and immunofluorescence in DRG cell; TUNEL staining microscopy was used to observe the apoptosis of DRG cells. The changes of endoplasmic reticulum and mitochondria were observed by transmission electron microscopy of DRG cells. Results Compared with the sham group, the model group showed a decreased MWT at all time points after surgery, up-regulation of DRG cell apoptosis, up-regulation of sig-1R and Bax, down-regulation of Bcl-2, swelling of endoplasmic reticulum, disruption of mitochondrial membrane and reduction of mitochondrial cristae in the DRG cell endoplasmic reticulum after surgery(P＜0.05).BD1047 group showed elevated MWT at the fifth and seventh postoperative days, down-regulation of DRG cell apoptosis, down-regulated expression of sig-1R and Box, up-regulated expression of Bcl-2 and slightly damaged endoplasmic reticulum as well as mitochondria of DRG cells compared with model group(P＜0.05). Conclusions Inhibition of sig-1R up-regulates mechanical withdrawal threshold and reduces DRG cell apoptosis in CCI rats.

Keywords

• neuropathic pain|sigma-1 receptor|dorsal root ganglion|apoptosis