Electroacupuncture Alleviates Pain-Related Emotion by Upregulating the Expression of NPS and Its Receptor NPSR in the Anterior Cingulate Cortex and Hypothalamus.

Zitong Xu,Junying Du,Xuaner Xiang,Haiju Sun,Jianqiao Fang,Sisi Wang,Junfan Fang

doi:10.1155/2020/8630368

Abstract

Objective Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; however, the underlying mechanism of its effects still needs to be elucidated. The NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. Here, we aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund's adjuvant- (CFA-) evoked conditioned place aversion (C-CPA). Materials and Methods. CFA injection combined with a CPA paradigm was introduced to establish the C-CPA model, and the elevated O-maze (EOM) was used to test the behavioral changes after model establishment. We further explored the expression of NPS and NPSR at the protein and gene levels in the brain regions of interest by immunofluorescence staining and quantitative real-time PCR. Results We observed that EA stimulation delivered to the bilateral Zusanli (ST36) and Kunlun (BL60) acupoints remarkably inhibited sensory pain, pain-evoked place aversion, and anxiety-like behavior. The current study showed that EA significantly enhanced the protein expression of this peptide system in the ACC and hypothalamus, while the elevated expression of NPSR protein alone was just confined to the affected side in the CeA. Moreover, EA remarkably upregulated the mRNA expression of NPS in CeA, ACC, and hypothalamus and NPSR mRNA in the hypothalamus and CeA. Conclusions These data suggest the effectiveness of EA in alleviating affective pain, and these benefits may at least partially be attributable to the upregulation of the NPS-NPSR system in the ACC and hypothalamus.

Highlights

Water and chow pellets were available ad libitum. e animals were allowed to acclimate to the housing facilities for one week before the formal test, and all experimental procedures were performed in specially equipped rooms between 08 : 00 and 18 : 00. is study was approved by the Institutional Animal Care and Use Committee (IACUC-20180319-12), and all animal procedures conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals
Since the Neuropeptide S (NPS)-NPSR system is vigorous in mobilizing the activation of glutamate and gamma-aminobutyric acid (GABA) transmission, it is speculated EA stimulation might arrive at the hypothalamus to reinforce the mRNA and protein expressions of this system and in turn activates a strand of cellular signaling pathways acting on the descending pathway including the periaqueductal gray (PAG), a crucial structure in the endogenous descending inhibitory system, to participate in the encoding and processing of affective pain
Earlier studies detected no NPSR mRNA expression in this area but did detect the signal in the lateral nucleus of the amygdala (LA), the basolateral nucleus of the amygdala (BLA), etc. [27, 29, 73]. e interesting discovery in our report was the significant increase in the NPSR expression on the ipsilateral side alone after EA stimulation

Summary

Objective

Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; the underlying mechanism of its effects still needs to be elucidated. e NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. We aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund’s adjuvant- (CFA-) evoked conditioned place aversion (C-CPA). Ese pain components occur through various pathways and interconnect with many brain areas like the anterior cingulate cortex (ACC) [2,3,4], hypothalamus [5, 6], and central amygdala (CeA) [7, 8]. Our data provide explicit prerequisites to hypothesize whether the NPS-NPSR system in the ACC, hypothalamus, and CeA mediates EA alleviation effects on pain-related emotion

Materials and Methods

Results

Discussion

Conclusions

Disclosure