摘要
目的:探讨c AMP-PKA信号通路在大鼠骨癌痛发生发展中的作用。方法:雌性SD大鼠52只,随机分为5组:正常组(n=8),假手术组(n=8),骨癌痛组(n=12),骨癌痛+生理盐水组(n=8)和骨癌痛+PKA抑制剂组(n=16)。各组于造模前3天、1天以及造模后1、3、5、7、10、14天分别测定热缩足阈值和机械缩足阈值。PKA抑制剂Rp-c AMPS(1 mmol/20μl)分别于造模后早期(3、4、5天)和造模后后期(7、8、9天)经鞘内注射(每天1次)。采用酶联免疫吸附法(ELISA)检测大鼠背根神经节(DRG)和脊髓中c AMP的浓度和PKA的活性。结果:造模后,大鼠DRG和脊髓中c AMP的浓度显著增高,PKA的活性明显增强,与假手术组相比,差异有统计学意义(P<0.01)。早期和后期给予PKA抑制剂Rp-c AMPS治疗,均能显著延迟或抑制骨癌诱发的热痛敏和机械痛敏(P<0.01)。结论:骨癌显著增强DRG和脊髓中c AMP-PKA信号通路的活性,该信号通路的异常活动在骨癌痛的产生和维持中起着重要作用,抑制该信号通路的激活能有效减轻骨癌痛。
Objective：To explore the role of cAMP-PKA signaling pathway in development of bone cancer pain in rats.Methods：Female SD rats （n =52） were randomly divided into 4 groups：normal （n =8）; sham （n =8）; Tumor cell implantation （TCI） （n =12）,TCI ＋ saline （n =8）,and TCI＋ PKA inhibitor （n =16）.Thermal hyperalgesia and mechanical allodynia were tested at-3,-1,1,3,5,7,10,and 14 postoperative day.PKA inhibitor Rp-cAMPS （1 mmol/20 μl） were intrathecally injected on 3,4 and 5 postoperative day （early phase） or 7,8,and 9 postoperative day （late phase）,respectively.The concentration of cAMP and activity of PKA in DRG and spinal cord （SC） were measured by ELISA.Results：TCI treatment significantly increased concentration of cAMP and the activity of PKA in both DRG and SC （P ＜ 0.01）.Spinal administration of a PKA inhibitor Rp-cAMPS in the protocol of the early phase or late phase significantly prevented and/ or suppressed TCI-induced thermal hyperalgesia and mechanical allodynia （P ＜ 0.01）.Conclusion：Bone cancer induces activation of cAMP-PKA in the primary sensory neurons and spinal cord.Activation of cAMP-PKA signaling pathway may play an important role in the induction and maintenance of bone cancer pain.Inhibition of cAMP-PKA signaling pathway results in reduction of bone cancer pain.
出处
《中国疼痛医学杂志》
CAS
CSCD
2015年第1期10-14,共5页
Chinese Journal of Pain Medicine
基金
国家自然科学基金(81320108012)
