Repeated forced swim stress affects the expression of pCREB and ΔFosB and the acetylation of histone H3 in the rostral ventromedial medulla and locus coeruleus.

Abstract

The rostral ventromedial medulla (RVM) and locus coeruleus (LC) play crucial roles in descending pain modulation 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 RVM and LC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in descending pain modulatory system in a rat model of stress-induced hyperalgesia. 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 RVM, whereas the FS induced a significant increase only in the acetylation of histone H3 in the LC. CFA injection into the hindpaw did not induce a significant change in those expression and acetylation. Quantitative image analysis demonstrated that the numbers of pCREB-, acetylated histone H3- and ΔFosB-IR cells in the RVM were significantly higher in the FS group than those in the naive group. The CFA injection after the FS did not affect the FS-induced increases in the expression of pCREB and ΔFosB and the acetylation of histone H3 in the RVM even though nullified the increase in the acetylation of histone H3 in the LC. These findings suggest different neuroplasticities between the RVM and LC after the FS, which may be involved in activity change of descending pain modulatory system after the CFA injection.