Role of CREB-binding protein in cyclooxygenase 2 expression in spinal cord in a rat model of neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of CREB-binding protein (CBP) in cyclooxygenase 2 (COX-2) expression in spinal cord in a rat model of neuropathic pain (NP).Methods Forty male SD rats weighing 220-250 g in which intrathecal catheter was successfully implanted were randomly divided into 4 groups (n=10 each)sham operation group (group Sham),group NP,negative control group (group NC) and group CBP.NP was induced by CCI at 5 days after successful implantation of the intrathecal catheter.Normal saline,negative lentivirus vector (RNAi-NC-LV) and CBP shRNA lentivirus vector (CBP RNAi-LV) 20 μl were injected intrathecally at 7 days after CCI in groups NP,NC and CBP,respectively.Paw withdrawal threshold to mechanical stimuli (MWT)and paw withdrawal latency to thermal stimulus (TWL) were measured at 1 day before operation and at 3,5,7,10,12 and 14 days after operation.The rats were sacrificed after the measurement of MWT and TWL at 14 days after operation and the lumbar segment of the spinal cord was then removed for determination of the expression of CBP,acetylated histone H3/H4 (Ac-H3,Ac-H4) and COX-2 protein (by immunohistochemistry),and CBP and COX-2 mRNA (by RF-PCR).Results Compared with group Sham,MWT and TWL were significantly decreased at different time points after operation in groups NP,NCand CBP,and the expression of CBP,Ac-H3,Ac-H4 and COX-2 protein,and CBP and COX-2 mRNA was up-regulated at 14 days after operation in groups NP and NC (P ＜ 0.05).Compared with group NP,MWT and TWL were significantly increased at 10,12 and 14 days after operation and the expression of CBP,Ac-H3,Ac-H4 and COX-2 protein,and CBP and COX-2 mRNA was downregulated at 14 days after operation in group CBP (P ＜ 0.05).Conclusion CBP is involved in the development of NP by up-regulating COX-2 expression and increasing histone H3 and H4 acetylation in spinal cord.