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Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain.Because small interfering RNA (siRNA) can inhibit NR2B expression,siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury.However,an efficient and safe vector for NR2B siRNA has not been discov-ered.This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain.Results show that intrathecal injection of WSLP/siRNA complexes for 3 days in-hibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%,respec-tively,compared with control rats (P < 0.01).Injection of WSLP complexed with scrambled siRNA,or PEI with siRNA did not show this inhibitory effect.Moreover,injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3,7,12,and 21 days,while injection of WSLP with scrambled siRNA or PEI with siRNA did not.These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.
Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Beecock small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat Neuropathic pain and possibly nerve injury. Despite, an efficient and safe vector for NR2B siRNA has not been discov-ered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP / siRNA complexes for 3 days in-hibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respec- tively, compared with control rats ( P <0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP / siRNA complexes significantly relieved neuropathic pain at 3,7,12, a nd 21 days while while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can deliver deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.