• H Imbe and A Kimura.
• Department of Physiology, Wakayama Medical University, Kimiidera 811-1, Wakayama City 641-8509, Japan. Electronic address: imbe@wakayama-med.ac.jp.
• Neuroscience. 2015 Aug 20;301:12-25.

AbstractExposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and ΔFosB and the acetylation of histone H3 in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in rats with stress-induced hyperalgesia. CFA injection into the hindpaw or FS (day 1, 10min; days 2-3, 20min) induced a significant increase in the expression of pCREB and ΔFosB and the acetylation of histone H3 in the IC. Quantitative image analysis showed that the numbers of ΔFosB-immunoreactivity (IR) cells in the bilateral anterior and posterior IC (AIC and PIC) were significantly higher in the CFA group (AIC R, 548.0±98.6; AIC L, 433.5±89.4; PIC R, 546.1±72.8; PIC L, 415.5±53.5) than those in the naive group (AIC R, 86.6±14.8; AIC L, 85.5±24.7; PIC R, 124.5±29.9; PIC L, 107.0±19.8, p<0.01). However the FS prior to the CFA injection enhanced the mechanical hyperalgesia and attenuated the expression of pCREB and ΔFosB and the acetylation of histone H3 in the IC. There was no significant difference in the numbers of ΔFosB-IR cells in the bilateral PIC between the FS+CFA and naive groups. These findings suggest neuroplasticity in the IC after the FS, which may be involved in the enhancement of CFA-induced mechanical hyperalgesia through dysfunction of the descending pain modulatory system.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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