Role of spinal neuronal CREB-regulated transcription coactivator 1 in maintenance of bone cancer pain in mice

Abstract

Objective To evaluate the role of spinal neuronal CREB-regulated transcription coactivator 1 (CRTC1) in the maintenance of bone cancer pain (BCP) in mice.Methods Thirty-two male C3H/HeJ mice,aged 4-6 weeks,weighing 20-25 g,were randomly divided into 4 groups (n =8 each):sham operation + normal saline group (group S),BCP + normal saline group (group BCP),BCP 4+ empty adenovirus vector Ad-EGFP group (group Ad-EGFP) and BCP + CRTC1 gene RNA interference adenovirus (Ad-CRTC1) group (group Ad-CRTC1).In BCP,Ad-EGFP and Ad-CRTC1 groups,the model of BCP was established by intramedullary injection of α-minimal essence media containing osteolytic NCTC 2472 cells into the right femur.In group S,the mice were inoculated with α-minimal essence media containing no tumor cells.Normal saline 5 μl,Ad-EGFP 5μl (in normal saline),and Ad-CRTC1 5 μl (in normal saline) were injected intrathecally in BCP,Ad-EGFP and Ad-CRTC1 groups,respectively,once a day for 3 consecutive days starting from day 14 after inoculation of the tumor cells.On 1 day before inoculation,on 4,7,10 and 14 days after inoculation and on 1,3,5 and 7 days after intrathecal injection (T0-s),the mechanical paw withdrawal threshold (MWT) and spontaneous lifting times were measured.Results Compared with the baseline value at T0,MWT was significantly decreased,and the spontaneous lifting times were increased at T1 in each group,no significant change was found in MWT and the spontaneous lifting times at T2 in group S,and MWT was gradually decreased,and the spontaneous lifting times were gradually increased with the prolonging time in BCP,Ad-EGFP and Ad-CRTC1 groups.Compared with group S,MWT was significantly decreased,and the spontaneous lifting times were increased in the other groups.MWT was significantly higher,and the spontaneous lifting times were lower at T5-8 in group Ad-CRTC1 than in BCP and AdEGFP groups.Conclusion Spinal neuronal CRTC1 is involved in the maintenance of BCP in mice. Key words: Bone neoplasms ; Pain ; Neurons ; Spinal cord ; CRTC protein