Abstract:

BACKGROUND: Some studies have shown that viral vectors can carry N-methyl-D-aspartic acid receptors 1 (NR1) small interference RNA (siRNA) to relieve inflammatory pain in rats, but the viral vectors are unsafe.
OBJECTIVE: To examine the potential application of a non-viral gene carrier, water soluble lipopolymer (WSLP) for delivering siRNA targeting NR1 in vitro and in vivo and to determine whether WSLP-NR1siRNA complexes can be a new method for neuropathic pain treatment.
METHODS: PC12 cells were randomly divided into three groups: group WSLP-negative NR1 siRNA (negative group), group polyethylenimine-NR1 siRNA (control transfection group) and group WSLP- NR1 siRNA (group WS). NR1 expressions were detected using reverse transcription-PCR and western blot analysis. Forty-eight healthy male Sprague-Dawley rats were randomly divided into four groups (n=12 in each group): sham operation group (sham group), neuropathic pain group (model group), group polyethylenimine-NR1 siRNA (group PEI) and group WSLP- NR1 siRNA (group WSLP). Neuropathic pain models were established in the latter three groups. Normal saline, PEI-NR1 siRNA complex and WSLP-NR1 siRNA were injected intrathecally in model, PEI and WSLP groups, respectively, at 1 day after operation. Only the sciatic nerve was exposed in the sham group.
RESULTS AND CONCLUSION: NR1 mRNA and protein expression significantly decreased in group WS as compared with negative and control transfection groups (P < 0.01). Compared with the sham group, NR1 mRNA and protein expression significantly increased in the model, PEI and WSLP groups, and cumulative pain scores in the latter three groups were also higher (P < 0.01). Compared with the model group, intrathecal injection of WSLP- NR1siRNA complexes could relieve neuropathic pain and inhibit NR1 gene expression with reductions in mRNA and protein levels (P < 0.01), and intrathecal injection of PEI-NR1siRNA complexes did not show this inhibitory effect (P > 0.05). These results demonstrate that WSLP not only efficiently delivers NR1 siRNA targeting NR1 in vivo and inhibits the expression of NR1, but also reduces neuropathic pain in rats.

Key words: biomaterials, biomaterials and controlled drug release, water-soluble liposomes, carrier drugs, N-methyl-D-aspartate receptor 1, small interfering RNA, PC12 cells, neuropathic pain, provincial grants-supported paper, biomaterial photographs-containing paper