Contribution of BDNF/TrkB signalling in the rACC to the development of pain-related aversion via activation of ERK in rats with spared nerve injury
作者
Wang, X;Zhang, L;Zhan, YF;Li, DP;Zhang, YG;Wang, GM;Zhang, MY
作者单位
[Wang, Xu; Zhan, Yufeng; Wang, Gongming; Zhang, Mengyuan] Shandong Univ, Dept Anesthesiol, Shandong Prov Hosp, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.;-;[Zhang, Le] Shandong Univ, Dept Anesthesiol, Hosp 2, Jinan 250033, Shandong, Peoples R China.;-;[Li, Dengping] PKU Care Luzhong Hosp, Dept Anesthesiol, Zibo 255400, Shandong, Peoples R China.;-;[Zhang, Yuangui] Weifang People Hosp, Dept Anesthesiol, Weifang 261041, Shandong, Peoples R China.
摘要
The rostral anterior cingulate cortex (rACC) is a key structure in mediating the negative affective component of chronic pain. Brain-derived neurotrophic factor (BDNF) is known to play a critical role in activity dependent synaptic plasticity, learning and memory. It has been shown that BDNF signalling in the rACC might be involved in spontaneous pain-related aversion, but its underlying mechanism is still largely unknown. To address this question, we measured the mRNA and protein levels of BDNF in the rACC after nerve injury and found that BDNF expression was markedly higher in nerve-injured rats than in controls. Moreover, we found that conditioned place avoidance (CPA), a behavioural phenotype reflecting pain related aversion, was acquired in rats with partial sciatic nerve transection. However, a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely suppressed this process. Importantly, we found that administration of exogenous BDNF into the rACC of intact rats was sufficient to produce CPA, while selectively blocking phosphorylated extracellular signal regulated kinase (p-ERK) with a mitogen-activated protein kinase (MAPK) inhibitor U0126 completely abolished the acquisition of BDNF-induced CPA. In conclusion, we demonstrate, for the first time, that ERK is an important downstream effector of the BDNF/TrkB-mediated signalling pathway in the rACC that contributes to the development of neuropathic pain-related aversion. (C) 2017 Elsevier B.V. All rights reserved.
关键词
ANTERIOR CINGULATE CORTEX; SPINAL DORSAL HORN; NEUROTROPHIC FACTOR; NEUROPATHIC PAIN; PROTEIN-KINASE; ANIMAL-MODEL; MAP KINASE; SYNAPTIC PLASTICITY; LIGATION MODEL; BACK-PAIN
基本信息
