Effects of intrathecally CREB antisense oligodeoxynucleotide on pain behaviors in a mouse model of chronic constriction injury of sciatic nerve / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effects of intrathecally cyclic AMP response element-binding protein(CREB) antisense oligodeoxynucleotide (ODN) on neuropathic pain behaviors.Methods Using mouse model of neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI),24 male C57BL/6 mice successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into 4groups(n=6)Saline group(NS),CREB sense ODN group(S),CREB missense ODN group(M),CREB antisense ODN group(A).Mice in NS,S,M and A were intrathecally treated with Saline 5μ l,Sense ODN 5μg/5μl,Missense ODN 5μg/5μl and Antisense ODN 5μg/Sμl once daily on day 1 ～6 after CCI respectively.Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency(PWTL) were tested on day 1 before CCI and day 1,3,5,7,10,14,17,21 after CC(I).Results Mice in A group maintained the pain thresholds in the baseline and lasted at least 7 days after CCI ( 7 d,PWMT( 0.81 ± 0.20 ) g vs ( 1.00 ± 0.19 ) g,P ＞ 0.05 ;PWTL(5.96 ± 0.69) s vs (6.93 ± 1.08 ) s,P ＞ 0.05 ).The withdrawal thresholds in the ipsilateral hind paws of the mouse were significantly lower than baseline in A group on day 10 after CCI( 10 d,PWMT(0.56 ±0.19)g vs (1.00±0.19)g,P＜0.05; PWTL(3.93 ±0.28)s vs (6.93 ± 1.08)s,P＜0.05).Compared with NS group ( 10 d,PWMT(0.56 ±0.19)g vs (0.37 ±0.08)g,P＜0.05; PWTL(3.93 ±0.28)s vs (3.14 ±0.45)s,P＜0.05),S group,M group,the withdrawal thresholds of A group was significantly elevated on day 10 after CCI.These effects lasted up to at least day 21 after CCI.Conclusion Intrathecally treated with CREB antisense ODN in the development of neuropathic pain induced by CCI completely improved pain behaviors during the course of injection,and the effects of relief pain lasted at least 15d after no injection.