Role of calcium/calmodulin-dependent protein kinase Ⅱ in up-regulation of expression of Cav3.2 T-type calcium channels in spinal cord in a rat model of neuropathic pain
10.3760/cma.j.issn.0254-1416.2012.10.016
- VernacularTitle:钙/钙调素依赖性蛋白激酶Ⅱ在神经病理性痛大鼠脊髓Cav3.2T型钙通道表达上调中的作用
- Author:
Xianjie WEN
;
Hua LIANG
;
Jiying ZHONG
;
Xueqin ZHENG
;
Xiaohong LAI
;
Hongzhen LIU
;
Hanbing WANG
;
Chengxiang YANG
- Publication Type:Journal Article
- Keywords:
Neuralgia;
Calcium-calmodulin-dependent protein kinase type 2;
Calcium channels,Ttype;
Spinal cord
- From:
Chinese Journal of Anesthesiology
2012;(10):1218-1221
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the up-regulation of expression of Cav3.2 T-type calcium channels in spinal cord in a rat model of neuropathic pain (NP).Methods Forty-eight male Sprague-Dawley rats,aged 3 months,weighing 220-250 g,were randomly divided into 6 groups (n =8 each)∶ sham operation group (group S),group NP,dimethyl sulfoxide group (group D) and different concentrations of a specific CaMK Ⅱ inhibitor KN93 groups (groups K1-3).NP was produced by chronic compression of dorsal root ganglion.The rats in groups D and K1-3 received a single intrathecal injection of dimethyl sulfoxide and KN93 15,30,60 nmol/L (10 μl),respectively,on 5th day after NP.Paw withdrawal threshold to von Frey filament stimulation (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured before NP,before intrathecal injection on 5th day after NP,and at 30 and 60 min and 3,6 and 8 h after intrathecal injection on 5th day after NP (T1-7).The rats were sacrificed after the measurement of pain threshold at T7 and their lumbar enlargements were removed to detect the expression of Cav3.2 mRNA and protein using Western blot and RT-PCR.Results Compared with group S,MWT was significantly decreased,TWL was shortened and the expression of Cav3.2 mRNA and protein was up-regulated in NP,D and K1-3 groups (P ＜ 0.05).Compared with NP group,MWT was significantly increased,TWL was prolonged and the expression of Cav3.2 mRNA and protein was down-regulated in a concentration-dependent manner in K1-3 groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group D (P ＞ 0.05).Conclusion CaMK Ⅱ is involved in the development and maintenance of chronic NP by up-regulating the expression of Cav3.2 T-type calcium channels in rat spinal cord.
