Chronic stress increases pain sensitivity via activation of the rACC-BLA pathway in rats.

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.