Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia

被引：20

作者：

Ji, Liu ^{[1
,2
]}

Chen, Yongmei ^{[3
]}

Wei, Huixia ^{[1
,2
]}

Feng, Hui ^{[1
,2
]}

Chang, Ruijie ^{[1
,2
]}

Yu, Di ^{[1
,2
]}

Wang, Xianyu ^{[1
,2
]}

Gong, Xingrui ^{[1
,2
,4
,5
]}

Zhang, Mazhong ^{[4
,5
]}

机构：

[1] Hubei Univ Med, Affiliated Hosp, Shiyan Taihe Hosp, Dept Anesthesiol, Shiyan, Hubei, Peoples R China

[2] Hubei Univ Med, Dept Anesthesiol, Inst Anesthesiol, Shiyan, Hubei, Peoples R China

[3] Hubei Univ Med, Affiliated Hosp, Shiyan Taihe Hosp, Dept Lab, Shiyan, Hubei, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Anesthesiol, Shanghai, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Pediat Clin Pharmacol Lab, Shanghai, Peoples R China

来源：

BRAIN RESEARCH | 2019年 / 1715卷

基金：

中国国家自然科学基金;

关键词：

Neuropathic pain; Alpha7 acetylcholine receptor; Dynorphin A; NICOTINE; ENHANCEMENT; SUPPRESSION; INHIBITION; ISCHEMIA; STRESS; INJURY; MODEL;

D O I：

10.1016/j.brainres.2019.03.016

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Dynorphin A is increased in neuropathic pain models. Activation of alpha 7 n acetylcholine receptor (nAchR) reduces inflammation and pain. Whether activation of alpha 7 nAchR affects dynorphin A release is unknown. The experiments evaluated the proinflammatory effect of dynorphin A in the spinal nerve ligation-induced neuropathic pain models and the effect of alpha 7 nAchR activation on the dynorphin A content. a alpha 7 nAchR agonist, PHA-543613 and its antagonist, methyllycaconitine citrate were used and dynorphin A content was measured after spinal nerve ligation and in microglia cultures to test the analgesic mechanisms of alpha 7 nAchR activation. The results showed that dynorphin A content peaked 3 to 7 days after nerve injury, and dynorphin A anti-serum intrathecal injection decreased IL-beta and TNF-alpha content a week after nerve injury. Activation of alpha 7 nAchR by PHA-543613 alleviated neuropathic pain behaviors and decreased dynorphin A concentration in the ipsilateral spinal cords. Also, PHA-543613 decreased dynorphin A release from the microglia cultures to LPS stimulation by activation of alpha 7 nAchR. Our results suggest that dynorphin A contribute to the development and maintenance of neuropathic pain and that decreasing dynorphin A content by activation of alpha 7 AchR of microglia is a potential therapeutic target for treating neuropathic pain.

引用

页码：57 / 65

页数：9