Wang Xu, Zhang Le, Zhan Yufeng, Li Dengping, Zhang Yuangui, Wang Gongming, Zhang Mengyuan
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
Department of Anesthesiology, The Second Hospital of Shandong University, Jinan 250033, Shandong Province, China.
Brain Res. 2017 Sep 15;1671:111-120. doi: 10.1016/j.brainres.2017.07.010. Epub 2017 Jul 18.
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.
喙前扣带皮层（rACC）是介导慢性疼痛负性情感成分的关键结构。脑源性神经营养因子（BDNF）在依赖活动的突触可塑性、学习和记忆中发挥关键作用。已有研究表明，rACC中的BDNF信号可能参与自发性疼痛相关厌恶，但其潜在机制仍 largely未知。为解决这个问题，我们测量了神经损伤后rACC中BDNF的mRNA和蛋白水平，发现神经损伤大鼠的BDNF表达明显高于对照组。此外，我们发现条件性位置回避（CPA），一种反映疼痛相关厌恶的行为表型，在部分坐骨神经横断的大鼠中出现。然而，向rACC局部注射BDNF-原肌球蛋白受体激酶B（TrkB）拮抗剂可完全抑制这一过程。重要的是，我们发现向完整大鼠的rACC中注射外源性BDNF足以产生CPA，而用丝裂原活化蛋白激酶（MAPK）抑制剂U0126选择性阻断磷酸化细胞外信号调节激酶（p-ERK）可完全消除BDNF诱导的CPA的形成。总之，我们首次证明，ERK是rACC中BDNF/TrkB介导的信号通路的重要下游效应器，其有助于神经性疼痛相关厌恶的发展。
