Effects of intrathecally postsynaptic density protein-95 antisense oligodeoxynucleotide on pain behaviors in mice model of neuropathic pain

Abstract

Objective To investigate the effects of intrathecally postsynaptic density protein-95 (PSD-95) antisense oligodeoxynucleotide on neuropathic pain behaviors of sciatic nerve ligation mouse. Methods Forty-eight male C57BL/6 mice in which intrathecal catheter was successfully implanted were randomly divided into 4 groups (n=12): Sham group, normal saline group (group NS), PSD-95 antisense oligodeoxynucleotide group (group A) and PSD-95 missense oligodeoxynucleotide group (group M). In groups NS, A and M, normal saline 5 μl, antisense oligodeoxynucleotide 5 μg/5 μl and missense oligodeoxynucleotide 5 μg/5 μl were injected intrathecally once a day for 14 d, starting from the 1st day after chronic constriction injury(CCI), respectively. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWL) were measured on day 1 before CCI and on day 1, 3, 5, 7, 14, 17, 21 after CCI. Results During day 1-day 14, mice in group A maintained the pain thresholds consistent with Sham group [14 d, PWMT(5.69±1.34) g, P>0.05, PWL (9.65±1.44) s, P>0.05]. The withdrawal thresholds in the ipsilateral hind paws of the group A were significantly lower than sham group on day 17 after CCI[PWMT(4.24±1.83) g, P<0.05, PWL(7.18±0.41) s, P<0.05]. However, compared with group NS [PWMT (1.77±0.38) g, P<0.05, PWL (4.33±1.21) s, P<0.05]and group M[PWMT (1.6±0.37) g, P<0.05, PWL(4.38± 0.95) s, P<0.05], the withdrawal thresholds of group A was significantly elevated on day 17 after CCI. Conclusions Intrathecally treated with PSD-95 antisense oligodeoxynucleotide in the development of neuropathic pain induced by CCI completely improved pain behaviors during the course of injection, and the effects of pain relief lasted at least 7 d after no injection. Key words: Neuropathic pain; postsynaptic density protein-95; Antisense oligonucleotide; N-methyl-D-aspartate