Analgesic efficacy of intrathecal p300 siRNA in a rat model of neuropathic pain

Objective To investigate the analgesic efficacy of intrathecal p300 small interfering RNA （siRNA） in a rat model of neuropathic pain. Methods Ninety-six male SD rats in which intrathecal catheter was successfully placed were used in this study. Neuropathic pain was induced by chronic constrictive injury （CCI）.Loosely constrictive ligatures were placed around the common sciatic nerve. The rats were randomly divided into 4 groups （n = 24 each）： sham operation ＋ normal saline （NS） group （group S）, CCI ＋ NS group （group CCI）,CCI ＋ transfection agent group （group Ⅴ） and CCI ＋ p300 siRNA group （group P）. Intrathecal NS 20 μl, transfection agent 20 μl or p300 siRNAs （in transfection agent） 20 μl was injected twice a day （10 μl every time） for 4consecutive days from 3 to 6 days after operation. Mechanical pain threshold and thermal pain threshold were measured at 1 day before operation （baseline） and at 1, 3, 5, 7, 9, 11, 14 days after operation. The animals were then killed and the lumbar segment of the spinal cord was removed at 3, 7 and 14 days after operation to detect the expression of p300 protein and mRNA and Ac-H3. Results Mechanical pain threshold and thermal pain threshold were significantly decreased at each time point after operation in group CCI, V and P compared with the baseline value （P 〈 0.05）. Mechanical pain threshold and thermal pain threshold were significantly decreased and the expression of p300 mRNA and protein and Ac-H3 was up-regulated in group CCI, V and P compared with group S （P 〈 0.05）. Mechanical pain threshold and thermal pain threshold were significantly increased, and the expression of p300 mRNA and protein and Ac-H3 was down-regulated in group P compared with group CCI （P 〈 0.05）.Conclusion Intrathecal p300 siRNA can attenuate the neuropathic pain in rats with CCI and the mechanism may be related to the inhibition of the expression of p300 and Ac-H3 in the spinal cord. Key words: RNA,small interfering; Injections,spinal; Neuralgia; Analgesia