Chronic stress increases pain sensitivity via activation of the rACC-BLA pathway in rats
Chronic stress increases pain sensitivity via activation of the rACC-BLA pathway in rats
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慢性应激通过激活大鼠的 rACC-BLA 通路增加疼痛敏感性
DOI：
10.1016/j.expneurol.2018.12.009
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发表时间：
2019-03-01
影响因子：
5.3
通讯作者：
Xing，Guo-Gang
中科院分区：
文献类型：
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作者：
Liu，Ling-Yu;Zhang，Rui-Ling;Xing，Guo-Gang
慢性应激可引起与疼痛相关的神经生物学改变，从而引起应激性痛觉过敏（SIH）。然而，其基本机制在很大程度上仍然未知。在以往的研究中，我们报道了杏仁核参与了慢性强迫游泳（FS）应激诱导的大鼠抑郁样行为和神经病理性疼痛的加重，其中杏仁核基底外侧核（BLA）和杏仁核中央核（CeA）在包括伤害感受在内的情感和感觉信息的整合中起重要作用。在此，我们使用在体多通道记录从喙前扣带皮层（rACC）和BLA，我们发现，慢性FS应激（CFSS）可以增加大鼠的疼痛敏感性，响应于低强度无害刺激（LIS）和高强度伤害性刺激（HNS）施加在后爪，验证了SIH在应激大鼠的发生。此外，我们发现CFSS不仅诱导rACC神经元群的活动增加，而且还产生了rACC局部场电位（LFP）的增强场电位功率（FPP），特别是在低频θ波段以及高频低γ波段范围内，无论是在基线状态下还是在LIS和HNS条件下。此外，通过互相关方法和部分定向相干（PDC）算法分析rACC和BLA的LFP振荡活动，我们证明CFSS可以显著促进rACC和BLA区域之间的同步，也增强了从rACC到BLA的神经信息流。结论：慢性FS应激可导致大鼠rACC神经元活性增加，促进rACC和BLA之间的功能连接和同步化，并增强rACC到BLA的疼痛相关神经信息流，这可能是SIH发病机制的基础。
Exposure to chronic stress can produce maladaptive neurobiological changes in pathways associated with pain processing, which may cause stress–induced hyperalgesia (SIH). However, the underlying mechanisms still remain largely unknown. In previous studies, we have reported that the amygdala is involved in chronic forced swim (FS) stress–induced depressive-like behaviors and the exacerbation of neuropathic pain in rats, of which, the basolateral amygdala (BLA) and the central nucleus of the amygdala (CeA) are shown to play important roles in the integration of affective and sensory information including nociception. Here, using in vivo multichannel recording from rostal anterior cingulate cortex (rACC) and BLA, we found that chronic FS stress (CFSS) could increase the pain sensitivity of rats in response to low intensity innoxious stimuli (LIS) and high intensity noxious stimuli (HNS) imposed upon the hindpaw, validating the occurrence of SIH in stressed rats. Moreover, we discovered that CFSS not only induced an increased activity of rACC neuronal population but also produced an augmented field potential power (FPP) of rACC local field potential (LFP), especially in low frequency theta band as well as in high frequency low gamma band ranges, both at the baseline state and under LIS and HNS conditions. In addition, by using a cross-correlation method and a partial directed coherence (PDC) algorithm to analyze the LFP oscillating activity in rACC and BLA, we demonstrated that CFSS could substantially promote the synchronization between rACC and BLA regions, and also enhanced the neural information flow from rACC to BLA. We conclude that exposure of chronic FS stress to rats could result in an increased activity of rACC neuronal population and promote the functional connectivity and the synchronization between rACC and BLA regions, and also enhance the pain–related neural information flow from rACC to BLA, which likely underlie the pathogenesis of SIH.