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Cyclic AMP-dependent positive feedback signaling pathways in the cortex contributes to visceral pain.

Journal of neurochemistry (2019-10-31)
Shui-Bing Liu, Xin-Shang Wang, Jiao Yue, Le Yang, Xu-Hui Li, Li-Ning Hu, Jing-Shan Lu, Qian Song, Kun Zhang, Qi Yang, Ming-Ming Zhang, Matteo Bernabucci, Ming-Gao Zhao, Min Zhuo
ABSTRACT

Cortical areas including the anterior cingulate cortex (ACC) play critical roles in different types of chronic pain. Most of previous studies focus on the sensory inputs from somatic areas, and less information about plastic changes in the cortex for visceral pain. In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch-clamp recording, behavioral tests, western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out mice. Integrative approaches were used to investigate possible changes of neuronal AC1 in the ACC after the injury. We found that AC1, a key enzyme for pain-related cortical plasticity, was significantly increased in the ACC in an animal model of irritable bowel syndrome. Inhibiting AC1 activity by a selective AC1 inhibitor NB001 significantly reduced the up-regulation of AC1 protein in the ACC. Furthermore, we found that AC1 is required for NMDA GluN2B receptor up-regulation and increases of NMDA receptor-mediated currents. These results suggest that AC1 may form a positive regulation in the cortex during chronic visceral pain. Our findings demonstrate that the up-regulation of AC1 protein in the cortex may underlie the pathology of chronic visceral pain; and inhibiting AC1 activity may be beneficial for the treatment of visceral pain.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, ascites fluid
Sigma-Aldrich
Zymosan A from Saccharomyces cerevisiae, for inducing inflamatory response
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid
Sigma-Aldrich
Monoclonal Anti-Synaptophysin antibody produced in mouse, clone SVP-38, ascites fluid
Sigma-Aldrich
CNQX, ≥98% (HPLC), solid
Sigma-Aldrich
Anti-SNAP-25 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-NR1 Antibody, CT, Upstate®, from mouse
Sigma-Aldrich
NB001, ≥98% (HPLC)